BEACHY et al.v.Beachy et al. V. Tas et al.

Patent Trials and Appeals Board

Apr 28, 2014

10682584 - (J) (P.T.A.B. Apr. 28, 2014)

BoxInterferences@uspto.gov Paper No. 607
Telephone: 571-272-4683 Filed: 28April 2014

UNITED STATES PATENT AND TRADEMARK OFFICE
PATENT TRIAL AND APPEAL BOARD
____________________

Interference 105,926 McK
Interference 105,949 McK
Technology Center 1600
____________________

SINAN TAS and OKTAY AVCI,
Patent 7,893,078 B2,
Junior Party,

v.

PHILIP A. BEACHY, MICHAEL K. COOPER
and JEFFREY A. PORTER,
Application 13/364,121,
and
PHILIP A. BEACHY, JAMES K. CHEN and
ANSSI JUSSI NIKOLAI TAIPALE,
Application 13/363,934
Senior Party.
____________________

Before: FRED E. McKELVEY, DEBORAH KATZ, and JOHN G. NEW,
Administrative Patent Judges.

McKELVEY, Administrative Patent Judge.

JUDGMENT
In view of the Decision on Motions (Paper 605) and the Third Redeclaration 1
(Paper 606), it is— 2
ORDERED that judgment be entered against junior party Sinan Tas and 3
Oktay Avci (Sinan Tas being the real party in interest) as to 4
2

(1) Count 3 of Interference 105,926 (Interference 105,926, 1
Paper 97.001, page 2) and 2
(2) Count 2 of Interference 105,949 (Interference 105,949, Paper 1, 3
page 8). 4
FURTHER ORDERED that Claims 1 of 1-23 of involved US Patent 5
7,893,078 B2 are CANCELED, 35 U.S.C. 135(a); and 6
FURTHER ORDERED that a copy of this judgment be entered in the 7
administrative records of 8
(1) Tas U.S. Patent 7,893,078 B2, 9
(2) Beachy application 13/364,121, and 10
(3) Beachy application13/363,934. 11
FURTHER ORDERED that a party seeking judicial review timely serve 12
notice on the Director of the United States Patent and Trademark Office. 13
37 C.F.R. §§ 90.1 and 104.2. 14

NOTICE: "Any agreement or understanding between parties to an interference, 15
including any collateral agreements referred to therein, made in connection with or 16
in contemplation of the termination of the interference, shall be in writing and a 17
true copy thereof filed in the Patent and Trademark Office before the termination 18
of the interference as between the said parties to the agreement or understanding." 19
35 U.S.C. 135(c); see also Bd.R. 205 (settlement agreements). 20
21
3

cc (via electronic mail): 1
2
Attorney for Tas: 3
4
Walter J. Steinkraus 5
Email: wsteinkraus@live.com 6
7
Dr. Sinan Tas, pro se 8
Email: sinan.tas1@gmail.com 9
10
Attorney for Beachy: 11
12
Anthony J. Zelano 13
Brion P. Heaney 14
John A. Sopp 15
Millen, White, Zelano & Branigan, PC 16
Email: Heaney@mwzb.com 17
Emai: zelano@mwzb.com 18
Email: sopp@mwzb.com 19
20
Oliver R. Ashe, Jr. 21
Ashe, PC 22
Email: oashe@ashepc.com 23
24
BoxInterferences@uspto.gov Paper 606
Telephone: 571-272-4683 Filed: 28 April 2014

UNITED STATES PATENT AND TRADEMARK OFFICE
PATENT TRIAL AND APPEAL BOARD
____________________

Interference 105,926 McK
Interference 105,949 McK
Technology Center 1600
____________________

SINAN TAS and OKTAY AVCI,
Patent 7,893,078 B2,
Junior Party,

v.

PHILIP A. BEACHY, MICHAEL K. COOPER
and JEFFREY A. PORTER,
Application 13/364,121,
and
PHILIP A. BEACHY, JAMES K. CHEN and
ANSSI JUSSI NIKOLAI TAIPALE,
Application 13/363,934
Senior Party.
____________________

Before: FRED E. McKELVEY, Administrative Patent Judge.

THIRD REDECLARATION

Consistent with the Decision on Motions (Paper 605) and other action taken 1
during the course of the interferences, the interferences are redeclared (37 C.F.R. 2
§ 41.203(c) (2013)) as follows: 3
2

Identification of the partes 1
Junior Party 2
Inventors: Sinan Tas (Turkey) 3
Oktay Avci (Turkey) 4
Patent: U.S. Patent 7,893,978 B2, issued 22 February 2011 5
based on application 10/682,584 6
filed 09 October 2003 7
Pat. Publication: 2010/0048725 A2 (25 February 2010) 8
Title: Use of cyclopamine in the treatment of basal 9
cell carcinoma and other tumors 10
Real party in interest: Sinan Tas 11
Senior Party—105,926 12
Inventors: Philip A. Beachy (Maryland) 13
James K. Chen (California) 14
Anssi Jussi Nikolai Taipale (Finland) 15
Application: 13/363,934, filed 01 February 2012 16
Title: Regulators of the hedgehog pathway, 17
compositions and uses related thereto 18
Real party in interest: Johns Hopkins University School of Medicine of 19
Baltimore, Maryland 20

Senior Party—105,949 21
Inventors: Philip A. Beachy (Maryland) 22
James K. Chen (California) 23
Jeffrey A. Porter (Massachusetts) 24
Application: 13/364,121, filed 01 February 2012 25
Title: Inhibitors of hedgehog signaling pathways, 26
compositions and uses related thereto 27
Real party in interest: Johns Hopkins University School of Medicine of 28
Baltimore, Maryland 29
3

Counts and claims of the parties 1
The counts are Count 2 and Count 3. There is no Count 1. Count 2 is the 2
sole count in Interference 105,949. Count 3 is the sole count in Interference 3
105,926. 4
Interference 105,926 5
Count 3 6
A method for treatment of a human subject having a basal cell 7
carcinoma tumor wherein Hedgehog/Smoothened signaling is utilized 8
for inhibition of apoptosis of the tumor cells, comprising 9

administering to the human subject a medicament comprising 10
cyclopamine or a pharmaceutically acceptable salt thereof, 11

wherein said medicament is administered in a dose that is 12
sufficient to induce apoptosis of said tumor cells and causes decrease 13
of size or disappearance of the tumor, 14

or 15

a method for treatment of a human subject having a basal cell 16
carcinoma tumor wherein Hedgehog/Smoothened signaling is utilized 17
for inhibition of apoptosis, comprising 18

administering to the human subject a medicament comprising 19
cyclopamine or a pharmaceutically acceptable salt thereof, 20

wherein said medicament is administered in a dose that is 21
sufficient to induce apoptosis of tumor cells and 22
causes decrease of size of the tumor. 23

The claims of the parties are: 24
Tas: 1-23—all designated as corresponding to Count 3 25
4

Beachy: 101-112 and 114-127—all designated as corresponding 1
to Count 3 2
With respect to Count 3, the parties have been accorded an earlier 3
constructive reduction to practice (i.e., benefit for the purpose of priority) of the 4
following applications: 5
Tas: PCT/TR01/00027 6
filed 02 July 2001 7
Beachy: Application 13/176,297 8
filed 05 July 2011 (Ex 1003) 9

Application 12/079,776 10
filed 28 March 2008 11
now US Patent 7,998,946 (Ex 1004) 12

Application 11/338,503 13
filed 23 January 2006 14
now US. Patent 7,7476,661 (Ex 1005) 15

Application 09/668,076 16
filed 13 October 2000 17
now U.S. Patent, 7,098,196 (Ex 1018) 18
Interference 105,949 19
Count 2 20
A method for treatment of a human subject having a basal 21
carcinoma tumor cell wherein Hedgehog/Smoothened signaling is 22
utilized for inhibition of apoptosis of the tumor cell, comprising 23

administering to the human subject a medicament comprising 24
cyclopamine, 25

wherein said medicament is administered in a dose that is 26
sufficient to induce apoptosis of said tumor cell and causes decrease 27
of size or disappearance of the tumor, 28
5

or 1

a method of therapy for a human subject having a basal cell 2
carcinoma tumor, comprising 3

administering to the human subject a therapeutically effective 4
amount of a medicament comprising cyclopamine and a 5
pharmaceutically acceptable carrier, 6

wherein in said tumor smoothened-dependent hedgehog 7
signaling is utilized for inhibition of apoptosis, and 8

said amount of cyclopamine selectively inhibits smoothened-9
dependent hedgehog signaling in said tumor and is sufficient to induce 10
apoptosis in said tumor and inhibits tumor cell proliferation. 11

The claims of the parties are: 12
Tas: 1-23—all designated as corresponding to Count 2 13
Beachy: 201-213—all designated as corresponding to Count 2. 14
With respect to Count 2, the parties have been accorded an earlier 15
constructive reduction to practice (i.e., benefit for the purpose of priority) of the 16
following applications: 17
Tas: PCT/TR01/00027 18
filed 02 July 2001 19
Beachy: Application 12/652,134 20
filed 05 January 2010 21

Application 11/270,984 22
filed 11 November 2005 23

Application 09/708,964 24
filed 08 November 2000 25
now US Patent 7,291,626 (Ex 1009) 26
6

Application 09/685,244 1
filed 10 October 2000 (Ex 2013)2
7

cc (via electronic mail): 1
2
Attorney for Tas: 3
4
Walter J. Steinkraus 5
Email: wsteinkraus@live.com 6
7
Dr. Sinan Tas, pro se 8
Email: sinan.tas1@gmail.com 9
10
Attorney for Beachy: 11
12
Anthony J. Zelano 13
Brion P. Heaney 14
John A. Sopp 15
Millen, White, Zelano & Branigan, PC 16
Email: Heaney@mwzb.com 17
Emai: zelano@mwzb.com 18
Email: sopp@mwzb.com 19
20
Oliver R. Ashe, Jr. 21
Ashe, PC 22
Email: oashe@ashepc.com 23
BoxInterferences@uspto.gov Paper 605
Telephone: 571-272-4683 Entered: 28 April 2014

UNITED STATES PATENT AND TRADEMARK OFFICE
PATENT TRIAL AND APPEAL BOARD
____________________

Interference 105,926 McK
Interference 105,949 McK
Technology Center 1600
____________________

SINAN TAS and OKTAY AVCI,
Patent 7,893,078 B2,
Junior Party,

v.

PHILIP A. BEACHY, MICHAEL K. COOPER
and JEFFREY A. PORTER,
Application 13/364,121,
and
PHILIP A. BEACHY, JAMES K. CHEN and
ANSSI JUSSI NIKOLAI TAIPALE,
Application 13/363,934,
Senior Party.
____________________

Before: FRED E. McKELVEY, DEBORAH KATZ, and JOHN G. NEW,
Administrative Patent Judges.

NEW, Administrative Patent Judge.

DECISION ON MOTIONS
37 C.F.R. § 41.125

Interferences 105,926 & 105,949

2

I. INTRODUCTION 1
A. Background 2
Interferences 105,926 and 105,949 are before a panel of the Board for a decision 3
on motions. 4
The interferences have been consolidated. Paper 5. 5
Except for initial declaration papers, all papers related to Interference 105,949 6
appear in the file of Interference 105,926. 7
References to papers are to papers in Interference 105,926 unless otherwise noted. 8
Oral argument was requested. Paper 338; Paper 340 (corrected copy). 9
We have determined that oral argument is not needed in this case. 10
Tas submissions often failed to comply with our rules and established practice as 11
set out in our Standing Order (Paper 2). 12
We have considered the record submitted by Tas, as well as the more traditional 13
record submitted by Beachy, with the view of reaching the merits to the extent possible. 14
B. Abbreviations 15
The following appreciations are used in the record and this opinion. 16
BCC Basal cell carcinoma 17
Bcl-2 A protein that affects programmed cell death or “apoptosis” 18
BCNS Basal cell nevus syndrome 19
Hh Hedgehog protein 20
Smo Smoothened protein 21
Interferences 105,926 & 105,949

3

C. Parties 1
1. Junior Party 2
The Junior Party is Sinan Tas and Oktay Avci (“Tas”
1
). 3
The real party-in-interest is Dr. Sinan Tas. Paper 15. 4
2. Senior Party 5
The Senior Party is (1) Philip A. Beachy, Michael K. Cooper and Jeffrey A. Porter 6
(Application 13/364,121) and (2) Philip A. Beachy, James K. Chen and Anssi Jussi 7
Nikolai Taipale (Application 13/363,934) (“Beachy”). 8
The real party-in-interest is Johns Hopkins University School of Medicine of 9
Baltimore, Maryland. Curis, Inc., is identified as a licensee. Genentech is identified as a 10
sub-licensee. Paper 10. 11
D. Subject matter involved in interferences 12
1. The counts 13
Counts 2 and 3 are involved in these consolidated interferences. 14
2. Count 2 15
Count 2 is involved in Interference 105,949. 16
Count 2 reads (Interference 105,949, Paper 1, page 8): 17
Count 2 18
A method for treatment of a human subject having a basal 19
carcinoma tumor cell wherein Hedgehog/Smoothened signaling is 20
utilized for inhibition of apoptosis of the tumor cell, comprising 21

1
“Tas” refers to the party Tas and Oktay. We will refer to inventor Tas as “Dr. Tas” to
distinguish between the party Tas and inventor Tas.

Interferences 105,926 & 105,949

4

administering to the human subject a medicament comprising 1
cyclopamine, 2

wherein said medicament is administered in a dose that is 3
sufficient to induce apoptosis of said tumor cell and causes decrease 4
of size or disappearance of the tumor,
2
5

or 6

a method of therapy for a human subject having a basal cell 7
carcinoma tumor, comprising 8

administering to the human subject a therapeutically effective 9
amount of a medicament comprising cyclopamine and a 10
pharmaceutically acceptable carrier, 11

wherein in said tumor smoothened-dependent hedgehog 12
signaling is utilized for inhibition of apoptosis, and 13

said amount of cyclopamine selectively inhibits smoothened-14
dependent hedgehog signaling in said tumor and is sufficient to induce 15
apoptosis in said tumor and inhibits tumor cell proliferation.
3
16
17
The claims of the parties are: 18
Tas: 1-23—all designated as corresponding to Count 2 19
Beachy: 201-213—all designated as corresponding to Count 2. 20

2
This alternative of the count is based in large measure on Claims 15 and 20 of Tas
Patent 7,893,078 B2 (Ex. 2001, cols. 13 and 14).

3
This alternative of the count is based in large measure on former Beachy Claim 27
(now Claim 201) (Ex. 1008, page 1) of Beachy application 13/364,121 (Ex.1003).

Interferences 105,926 & 105,949

5

With respect to Count 2, the parties have been accorded an earlier constructive 1
reduction to practice (i.e., benefit for the purpose of priority) of the following 2
applications: 3
Tas: None 4
Beachy: Application 12/652,134 5
filed 05 January 2010 6

Application 11/270,984 7
filed 11 November 2005 8

Application 09/708,964 9
filed 08 November 2000 10
now US Patent 7,291,626 (Ex 1009) 11

Application 09/685,244 12
filed 10 October 2000 (Ex 2013) 13

3. Count 3 14
Count 3 is involved in Interference 105,926. 15
Count 3 reads (Paper 97.001, page 2): 16
Count 3 17
A method for treatment of a human subject having a basal cell 18
carcinoma tumor wherein Hedgehog/Smoothened signaling is utilized 19
for inhibition of apoptosis of the tumor cells, comprising 20

administering to the human subject a medicament comprising 21
cyclopamine or a pharmaceutically acceptable salt thereof, 22

Interferences 105,926 & 105,949

6

wherein said medicament is administered in a dose that is 1
sufficient to induce apoptosis of said tumor cells and causes decrease 2
of size or disappearance of the tumor,
4
3

or 4

a method for treatment of a human subject having a basal cell 5
carcinoma tumor wherein Hedgehog/Smoothened signaling is utilized 6
for inhibition of apoptosis, comprising 7

administering to the human subject a medicament comprising 8
cyclopamine or a pharmaceutically acceptable salt thereof, 9

wherein said medicament is administered in a dose that is 10
sufficient to induce apoptosis of tumor cells and causes decrease of 11
size of the tumor.
5
12

The claims of the parties are (Paper 1, pages 9-10): 13
Tas: 1-23—all designated as corresponding to Count 3 14
Beachy: 101-112 and 114-127—all designated as corresponding to 15
Count 3 16
With respect to Count 3, the parties have been accorded an earlier constructive 17
reduction to practice (i.e., benefit for the purpose of priority) of the following 18
applications: 19
Tas: None 20

4
This alternative of the count is based in large measure on Claims 15 and 20 of Tas
Patent 7,893,078 B2 (Ex. 2011, cols. 13 and 14).

5
This alternative of the count is based in large measure on former Beachy Claims 62-63
(now Claims115-116) (Ex. 1002, page 1) of Beachy application 13/363,934 (Ex. 1001).

Interferences 105,926 & 105,949

7

Beachy: Application 13/176,297 1
filed 05 July 2011 (Ex. 1003) 2
3
Application 12/079,776 4
filed 28 March 2008 5
now US Patent 7,998,946 (Ex. 1004) 6
7
Application 11/338,503 8
filed 23 January 2006 9
now US. Patent 7,7476,661 (Ex. 1005) 10
11
Application 09/668,076 12
filed 13 October 2002 13
now U.S. Patent, 7,098,196 (Ex. 1018) 14
15
E. Subject matter involved 16
To perform their normal functions, cells must transmit signals within their own 17
internal environment as well as transmit to and receive signals from other cells. 18
One such “signaling pathway” is called the “Hedgehog/Smoothened” cell signaling 19
pathway because it involves two proteins: “Hedgehog” and “Smoothened.” 20
The Hedgehog/Smoothened pathway relays information from the environment 21
outside of the cell to the interior of the cell where the information can cause a specific 22
effect. 23
The parties agree that it was known that tumor cell growth could be an effect of 24
signaling along the Hedgehog/Smoothened pathway. Paper 179, at 1; Ex. 2098, ¶ 12. 25
Tumors occur when cells grow or “proliferate” uncontrollably. Paper 96, at 1; 26
Ex. 2098, ¶ 48. 27
Often, cells in the body go through a process called “apoptosis,” wherein a cell 28
receives regular signals that trigger it to undergo programmed cell death. Id. 29
Interferences 105,926 & 105,949

8

A mutation in the signaling pathway for initiating apoptosis may prevent this 1
normally-programmed cell death and can lead to the formation of tumors resulting from 2
the cells proliferating in an uncontrolled manner. (Paper 96, at 1; Ex. 2098, ¶ 49.) 3
The Counts recite the administration of a drug called cyclopamine to a specific 4
type of tumor cell, a basal carcinoma cell (“BCC”). 5
Cyclopamine takes advantage of the Hedgehog/Smoothened apoptosis signaling 6
pathway to initiate apoptosis, which inhibits the BCCs from proliferating. 7
Cyclopamine is a steroid alkaloid having the chemical formula shown below: 8
9
Ex. 2001, col.2, ll. 5-15. 10
A dispute in this case involves the relationship of the effects of cyclopamine on 11
apoptosis, tumor cell proliferation, and the size and appearance of the tumor. 12
13
II. Tas Motion 2 14
A. Tas motion—no interference-in-fact 15
Tas moves for entry of judgment based on no interference-in-fact. Paper 196. 16
The motion is limited to Count 2 (Interference 105,949). 17
Interferences 105,926 & 105,949

9

Contingent on Tas Motion 2 being granted, Tas further moves for entry of orders 1
related to “case management” of Interference 105,949. 2
According to Tas, to succeed on the motion “Tas must show that the alternatives of 3
the count [Count 2] define patentably distinct inventions such that the subject matter of 4
one [alternative of Count 2 assumed to be prior art and] taken with the prior art does not 5
render the other [alternative of Count 2] obvious. Paper 196, page 1:23-25. 6
B.. Beachy opposition 7
Beachy opposed. Paper 320. 8
According to Beachy, for Tas “[t]o succeed on its motion, Tas was required to 9
prove that [the subject matter of]. . . Tas’ involved claims 1-23, . . . treated as prior art, 10
would [not] have anticipated or rendered obvious any one of Beachy’s involved claims 11
201-213 and [sic—“or”] vice versa.” Paper 320, page 5:14-17. 12
Further according to Beachy, Tas did not conduct a proper “analysis and, therefore, 13
did not satisfy its burden for the requested relief.” Paper 320, page 5:23-24. 14
C. Applicable principles 15
An interference exists only if there is an interference-in-fact. “An interference 16
exists if the subject matter of a claim of one party [Tas in this case] would, if prior art, 17
have anticipated or rendered obvious the subject matter of a claim of the opposing party 18
[Beachy in this case] and vice versa.” 37 C.F.R. § 41.203(a). 19
Section 41.203(a) codifies
6
in more explicit language a Board interpretation of 20
former Rule 1.601(j),
7
an interpretation found to be lawful by the Federal Circuit.
8
21

6
See (1) Notice of Proposed Rulemaking, 68 Fed. Reg. 66648, 66664 (col. 3 to 66665
(col. 1) (Nov. 26, 2003) and (4) Notice of Final Rule, 69 Fed. Reg. 49960, 49969 (col. 1)
(Aug. 12, 2004).
Interferences 105,926 & 105,949

10

When an interference is declared, an interference-in-fact is presumed to exist. 1
Case v. CPC International, Inc., 730 F.2d 745, 750 (Fed. Cir. 1984) (there is a 2
presumption that an interference-in-fact exits and a party contending otherwise has the 3
burden of proof); Bronshtein v. Roser, 61 USPQ2d 1745, 1753 (BPAI 2001) (when an 4
interference is declared, there is a presumption that there is an interference-in-fact). 5
D. Analysis 6
1. 7
Tas and Beachy appear to have a disagreement over whether Tas has made a 8
proper comparison of claimed subject matter, i.e., whether Tas compared the subject 9
matter of Tas claims vis-à-vis Beachy claims. 10
Beachy maintains that comparison of alternatives of Count 2 does not constitute a 11
comparison of Tas claims vis-à-vis Beachy claims. 12

7
Rule 1.601(j) (37 C.F.R. § 1.601(j) (2004)): “An interference-in-fact exists when at
least one claim of a party that it designated to correspond to a count and at least one claim
of an opponent that is designated to correspond to the count define the same patentable
invention.” The Board interpreted the rule to require a “two-way” test, i.e., the claim of
the party had to anticipate or render obvious the subject matter of a claim of the opponent
as vice versa. See, e.g., Winter v. Fujita, 53 USPQ2d 1234, 1243 (BPAI 1999),
reconsideration denied, 53 USPQ2d 1478 (BPAI 2000) (resolution of interference-in-fact
issue involves two-way analysis) Pechiney v. Cryovac, Inc., Interference 105,092, Paper
67, pages 3-4 (BPAI June 30, 2004) (cited by Beachy at Paper 320, pages 3-4)..

8
Eli Lilly and Co. v. Board of Regents of the University of Washington, 334 F.3d 1264
(Fed. Cir. 2003) (Board interpretation of its rule to require a two-way test for
interference-in-fact held to be lawful).

Interferences 105,926 & 105,949

11

Our review of the motion reveals that Tas essentially has compared some Tas 1
claims with some Beachy claims. Tas claims 15 and 20 (one alternative of the count) 2
were analyzed by Tas vis-à-vis Beachy claim 27 (now Beachy Claim 201) (another 3
alternative of the count). 4
Therefore we will decide the motion on the basis of a comparison of Tas Claim 20 5
vis-à-vis Beachy Claim 201. 6
As will become apparent, the significant limitation of Tas Claim 20 (which appears 7
in independent Tas Claims 15) is “causes decrease of size or disappearance of the tumor” 8
and the significant limitation of Beachy Claims 201 is “inhibits basal tumor cell 9
proliferation”. 10
2. 11
Tas Claim 15 reads (italics added): 12
A method for treatment of a human subject having a tumor 13
wherein Hedgehog/Smoothened signaling is utilized for inhibition of 14
apoptosis of the tumor cells, comprising 15
16
administering to the subject a medicament comprising 17
cyclopamine or another compound that selectively inhibits 18
Hedgehog/Smoothened signaling, 19
wherein said medicament is administered in a dose that is 20
sufficient to induce apoptosis of said tumor cells and causes decrease 21
of size or disappearance of the tumor. 22

Tas Claim 20 reads (italics added): 23
A method according to claim 15, wherein said tumor is basal 24
cell carcinoma or trichoepithelioma or a melanocytic tumor. 25
26
Paper 16. 27

Interferences 105,926 & 105,949

12

The Tas alternative of Count 3 reads: 1
A method for treatment of a human subject having a basal
9
2
carcinoma tumor cell wherein Hedgehog/Smoothened signaling is 3
utilized for inhibition of apoptosis of the tumor cell, comprising 4
5
administering to the human subject a medicament comprising 6
cyclopamine, 7
8
wherein said medicament is administered in a dose that is 9
sufficient to induce apoptosis of said tumor cell and causes decrease 10
of size or disappearance of the tumor. 11
12
Paper No. 196, page 1. 13
14
Beachy Claim 201 reads (italics added): 15
A method of therapy for a human subject having a basal cell 16
carcinoma tumor, 17
18
comprising administering to the subject a therapeutically 19
effective amount of a medicament comprising cyclopamine and a 20
pharmaceutically acceptable carrier, 21
wherein in said tumor smoothened-dependent hedgehog 22
signaling is utilized for inhibition of apoptosis, and 23
24
said amount of cyclopamine selectively inhibits smoothened-25
dependent hedgehog signaling in said tumor and is sufficient to induce 26
apoptosis in said tumor and inhibits tumor cell proliferation. 27
28
Paper 11. 29
30

9
The reference to “basal” cell comes from Claim 20 and narrows “tumor” as it appears
in Claim 15 to “basal” cell tumors.

Interferences 105,926 & 105,949

13

The Beachy alternative of Count 2 reads (italics added): 1
a method of therapy for a human subject having a basal cell 2
carcinoma tumor, comprising 3
4
administering to the human subject a therapeutically effective 5
amount of a medicament comprising cyclopamine and a 6
pharmaceutically acceptable carrier, 7
8
wherein in said tumor smoothened-dependent hedgehog 9
signaling is utilized for inhibition of apoptosis, and 10
11
said amount of cyclopamine selectively inhibits smoothened-12
dependent hedgehog signaling in said tumor and is sufficient to induce 13
apoptosis in said tumor and inhibits tumor cell proliferation. 14
15
Paper 196, page 1. 16
17
3. 18
The claim chart in Table 1 set out below compares the limitations of Tas 19
Claim 20 and Beachy Claim 201 (italics added). 20

Table 1
Tas Claim 20 Beachy Claim 201
A method for treatment of a human
subject having a basal cell carcinoma
tumor

A method of therapy for a human
subject having a basal cell carcinoma
tumor
comprising comprising
administering to the subject a
medicament comprising [a dose of]
cyclopamine . . .
administering to the subject a
therapeutically effective amount
of a medicament comprising
Interferences 105,926 & 105,949

14

cyclopamine . . .
that selectively inhibits
Hedgehog/Smoothened signaling
wherein said medicament is
administered in a dose that

said amount of cyclopamine selectively
inhibits smoothened-dependent
hedgehog signaling in said tumor and
is sufficient to induce apoptosis of said
basal tumor cells and causes decrease of
size or disappearance of the tumor.
is sufficient to induce apoptosis in said
basal tumor and inhibits basal tumor
cell proliferation.

According to Tas, “causes decrease of size or disappearance of the tumor” is not 1
the same as “inhibits basal tumor cell proliferation. Paper 196, page 6:1-12. 2
Further according to Tas, “[t]he Beachy . . . [Count 2] alternative does not require 3
tumor shrinkage or disappearance.” Paper 196, page 7:6-7. 4
Beachy states that “[as] used . . . [in its application], ‘proliferating’ and 5
‘proliferation’ refer to cells undergoing mitosis [i.e., cell division].” Ex. 1010, ¶ 0078. 6
If proliferation is inhibited, then the tumor does not grow. 7
Overlooked by Tas is the limitation “sufficient to induce apoptosis,” which appears 8
in both Tas Claim 20 and Beachy Claim 201. 9
According to Tas, “apoptosis is a regulated active cell death”, in this case death 10
of a BCC tumor cell. Paper 92, page 1:13. See also involved Tas Patent, Ex. 2001, 11
col. 2:42 describing “apoptotic death and removal of these tumor cells….”
10
12

10
We have found the word “apoptosis” only in the claims of involved Beachy
application 13/364,121 (Ex. 1008) (published as US Patent Application Publication
2012/0183603 A1) (Ex. 2010). In connection with a discussion of the central nervous
system, the word “apoptotic” appears in ¶ 0190 of the published application. .

Interferences 105,926 & 105,949

15

When the BCC tumor cells die, (1) the tumor decreases in size and possibly 1
disappears as recited by Tas and (2) the tumor cells stop proliferating as recited by 2
Beachy. 3
In effect, both Tas and Beachy recite “result” limitations in their respective claims 4
that are a consequence of apoptosis having taken place, that in turn is a consequence of 5
treating a human subject having a basal cell carcinoma tumor with cyclopamine. 6
The results recited in both sets of claims are not inconsistent because when a tumor 7
decreases in size or disappears, its cells have stopped proliferating. 8
We have not overlooked the fact that Tas states the following in its patent 9
(Ex. 2001, col. 11:47-53) (italics added): 10
It is also clear that the therapeutic effectiveness described herein and 11
the rapid disappearance of treated tumors could not be possible 12
without the causation of tumor cell apoptosis since merely inhibiting 13
or slowing the tumor cell proliferation by cyclopamine would, at best, 14
help one only to keep the tumor at its pre-treatment size. 15

Beachy Claim 201 is not limited to “merely inhibiting . . . tumor cell proliferation 16
by cyclopamine”; it also requires apoptosis. 17
Interferences 105,926 & 105,949

16

4. 1
(a) 2
Tas argues that the second alternative of Count 2 (Beachy Claim 201) should be 3
construed to be directed to a treatment wherein any cyclopamine dose producing 4
inhibition of proliferation of tumor cells would also produce their apoptosis. Paper 196, 5
page 4:7-9. 6
Tas continues to say that its “patent and priority application PCT/TR01/00027 have 7
shown[
11
] that this is not the case with administration [of] cyclopamine to BCC tumors.” 8
Paper 196, page 4:10-11. 9
We fail to see the relevance of the argument. 10
Beachy Claim 201 calls for the dose to “be sufficient to induce apoptosis”. 11
Accordingly, if some dose does not induce apoptosis, then the dose would not fall 12
within the scope of Beachy claim 201. 13
(b) 14
Tas argues that the subject matter of Beachy Claim 201 is not enabled by the 15
Beachy specification. Paper 196, page 6:5-6. 16
The argument is irrelevant. 17
In the context of a motion based on no interference-in-fact, the specifications of 18
both parties are presumed to be enabling and patentable over the prior art. 19
The premise of a no interference-in-fact motion is that while an opponent is 20
assumed to have prevailed on priority (and therefore is prior art), the party is nevertheless 21

11
A specification is not admissible to prove the truth of statements contained therein.
Standing Order, ¶ 152.2.1 (Paper 2, page 42). Nevertheless, we have considered the
specifications for what is described therein.

Interferences 105,926 & 105,949

17

entitled to its claims because the subject matter claimed by the opponent does not 1
anticipate or render obvious the subject claimed by the party. 2
Proof of an embodiment to establish priority necessarily involves proof that the 3
embodiment is enabling. 4
If a party believes that an opponent’s specification is not enabling, then the proper 5
procedure is to list a motion for judgment based on lack of enablement in addition to a 6
motion based on no interference-in-fact. 7
Moreover, a motion based on no interference-in-fact is a threshold motion which 8
can terminate an interference. 9
In terminating the interference on the threshold issue of no interference-in-fact a 10
party does not get a pre-grant chance to attack an opponent’s application or a post-grant 11
chance to attack an opponent’s patent. 12
(c) 13
We have considered all other arguments made by Tas and find them unconvincing. 14
E. Decision 15
Tas Motion 2 will be denied. 16
17
F. Contingent request 18
Continent on Tas Motion 2 being granted, Tas requests that the interference not be 19
terminated to permit certain “case management.” Paper 196, page 1:1-3. 20
The request was not authorized as part Tas Motion 2 or otherwise authorized as a 21
motion. 22
In any event, because Tas Motion 2 has been denied, there is no occasion to 23
consider or decide the contingent request by Tas that the interference not be terminated. 24
Interferences 105,926 & 105,949

18

The contingent request made by Tas will be dismissed. 1
2
III. Tas Motion 3 3
A. Background and discussion 4
Tas Motion 3 seeks entry of an order according Tas an earlier constructive 5
reduction to practice (i.e., benefit for the purpose of priority) of PCT/TR01/000027, filed 6
on 2 July 2001 (published as WO 02/078703 (the “’703 application”)). Paper 195, 7
page 1. 8
Beachy Opposition 3 (Paper 321) states in relevant part (italics added): 9
Beachy does not consider . . . [Tas Motion 3] to be necessary/relevant 10
to the ultimate determination of priority for either Count 2 of Count 3. 11
Nevertheless, Beachy does not oppose the Board considering and 12
rendering a substantive decision . . . [Tas Motion 3]. For clarity of the 13
record and to avoid any inference that Beachy admits any factual 14
assertion in . . . [Tas Motion 3], Beachy hereby denies all factual 15
assertions in . . . [Tas Motion 3] . . . .” 16

The relevance of Tas Motion 3 is that if (1) Tas Motion 3 is granted and (2) Tas 17
Motions 4 and 17 seeking to deny Beachy benefit are also granted, Tas becomes senior 18
party. 19
Tas argues that the ’703 application describes enabled embodiments within the 20
scope of Counts 2 and 3. Paper 195, page 16. 21
On the merits, Beachy does not oppose because a mere denial of all facts asserted 22
by Tas is not a response on the merits. 23
We agree with Tas that the ’703 application describes enabled embodiments 24
within, and constitutes a constructive reduction to practice of, an invention within the 25
scope of Counts 2 and 3. Hunt v. Treppschuh, 523 F.2d 1386, 1389 (CCPA 1975) (an 26
Interferences 105,926 & 105,949

19

application need only disclose a single enabled embodiment within the scope of the count 1
to constitute a constructive reduction to practice of the invention of the count); see also 2
Weil v. Fritz, 572 F.2d 856, 865 n.16 (CCPA 1978) (“as Hunt v. Treppschuh *** 3
explains, ‘the § 112 paragraph, requirements need only be met for an embodiment within 4
the count’ … where the count is drawn to a genus and the previously-filed application 5
discloses only a species thereof”); Falkner v. Inglis, 448 F.3d 1357, 1362 (Fed. Cir. 2006) 6
(same). 7
Claim charts appearing on pages 3-15 of the motion adequately set out how an 8
enabled embodiment of the subject matter of Counts 2 and 3 is described in the 9
ʼ703 application. 10
Beachy does not explain why the claim charts are not adequate for the purpose on 11
which they are relied. 12
13
B. Decision 14
Tas Motion 3 will be granted. 15
As to Counts 2 and 3 Tas is accorded an earlier constructive reduction to practice 16
as of 2 July 2001 based on the ʼ703 application. 17
18
IV. Tas Motion 4 19
Tas Motion 4 seeks entry of an order denying Beachy earlier constructive 20
reductions to practice as to Count 3. Paper 197. 21
Earlier constructive reductions to practice based on (1) Beachy application 22
13/363,934 (the “’934 application”) (Ex. 2147) and Beachy application 09/688,076 (the 23
Interferences 105,926 & 105,949

20

“’076 application”) (Ex. 1018)
12
(filed October 13, 2000) were accorded to Beachy when 1
Interference 105,926 was declared. Paper 1, pages 9-10. 2
According to Tas, the ’076 application does not describe an enabling embodiment 3
within the scope of either alternative of Count 3. Paper 197, pages 1 and 18. 4
Count 3 is reproduced earlier in this opinion. 5
Tas presents several arguments in support of its motion. 6
7
Motion 4 Limitation (1) 8
A method for treatment of a human subject having 9
a basal cell carcinoma tumor 10
Tas maintains that the Beachy ʼ076 application has no support for Limitation (1).
Paper 197, page 21:13-14.
Tas argues that the Beachy’076 application does not have a working example of a
method for treatment of a human subject having a basal cell carcinoma (BCC) tumor as
recited in Count 3. Paper 197, page 21.
According to Tas, the ’076 application has no example of a treatment of a human 11
having BCC or any other tumor, nor does it describe a treatment of another animal, e.g., a 12
mouse, having a naturally occurring tumor. Id. 13
Tas argues that there is nothing in the ’076 application from which a skilled person 14
could reasonably expect that a treatment of a tumor bearing human characteristics will 15
likely be applicable, let alone effective. Id. 16
Further according to Tas, nothing in the ’076 application made the treatment for 17
tumor-bearing humans as shown in Ex. 2004 (Tas International Application 18

12
The ’076 application issued as US Patent 7,098,196 B1 on 29 August 2006.
Interferences 105,926 & 105,949

21

WO 02/078703) expected or anticipated. By “expected or anticipated” we think Tas 1
argues that one skilled in the art would not have a reasonable expectation of success 2
based on the ʼ076 application. 3
Rather, Tas seems to contend that the actual experimental results reported by 4
Beachy and the prior art teach against it. Paper 197, page 22 (citing Tas testimony set 5
out in Ex. 2098 at ¶¶ 12, 13, 20-24, 27, 36, 40 and references therein). 6
Tas argues further that a statement of an ability of subject compounds (those 7
described as useful by Beachy) to block pathway activity in cells suggests that they may 8
be broadly useful in the treatment of certain sporadic tumors, and that mentioning BCC 9
as being one of the “certain sporadic tumors,” does not show possession of a treatment of 10
a human having BCC. Paper 197, page 22 (citing Beach US Patent 7,098,196 B1, 11
Ex.1018, col. 67, ll.27-40—the patent is based on the Beachy ʼ076 application). 12
Tas argues that statements made in the ’076 application that the disclosed tumor 13
treatment will be effective in a human patient would not lead a person of ordinary skill to 14
conclude that it would likely be applicable, let alone effective. Paper 197, page 23. 15
Tas contends that, at the time the ’076 patent was constructively reduced to 16
practice (i.e., “filed”), the art had not shown a treatment of either a human or an animal 17
using cyclopamine or another selective inhibitor of Hh signaling sufficient to satisfy a 18
skilled person that the treatment would be applicable or effective in humans (i.e., that a 19
likelihood of success would have been expected). Id. 20
Beachy responds that the ’076 application describes the treatment of BCC tumors 21
in humans. Paper 322, page 7. 22
Beachy quotes the following portions of the ’076 application to support its 23
contention (Paper 322, page 8 (bold in original), citing Ex. 1018, col. 48:16-22): 24
Interferences 105,926 & 105,949

22

In still another embodiment, the subject method can be used in 1
the treatment of human cancers, particularly basal cell 2
carcinomas and other tumors of epithelial tissues such as the skin. 3
For example, subject compounds can be employed, in the subject 4
method, as part of a treatment for basal cell nevus syndrome (BCNS), 5
and other . . . human carcinomas, adenocarcinomas, sarcomas and the 6
like. 7

The ’076 application also states (Paper 322, page 8 (bold in original), citing 8
Ex. 1018, col. 50:13-18): 9
These compounds may be administered to humans and other 10
animals for therapy by any suitable route of administration, including 11
orally, nasally, as by, for example, a spray, rectally, intravaginally, 12
parenterally, intracisternally and topically, as by powders, ointments 13
or drops, including buccally and sublingually. 14

The ‘076 application goes on to further state (Paper 322, page 8 (bold in 15
original), citing Ex. 1018, col. 66:3-19):, 16
Whatever the mechanism, such inhibitors may have utility in 17
trea[t]ment of disorders caused by inappropriate Shh pathway 18
activation. Patients with Basal Cell Nevus Syndrome (also termed 19
Gorlin's syndrome), an autosomal dominant disorder associated with 20
heterozygous loss-of function mutations in the human Ptc1 gene, 21
display increased incidence of numerous tumors, most notably 22
basal cell carcinoma (BCC), medulloblastoma, rhabdomyosarcoma 23
and fibrosarcoma. Loss-of-function mutations in Ptc1 or activating 24
mutations in Smo in addition are found in ~40% of sporadic BCC and 25
~25% of primitive neuroectodermal tumors. The ability of 26
cyclopamine and its derivatives to block pathway activation by both 27
of these types of mutations suggests that these plant-derived 28
compounds or others that influence the activity of Smo may be 29
valuable as therapeutic agents. 30

Interferences 105,926 & 105,949

23

The ʼ076 defines effective amount as follows (Paper 322, pages 8-9, citing 1
Ex. 1018, col. 10:8-15): 2
An “effective amount” of a subject compound, with respect to 3
the subject method of treatment, refers to an amount of the antagonist 4
in a preparation which, when applied as part of a desired dosage 5
regimen brings about, e.g., a change in the rate of cell proliferation 6
and/or the state of differentiation of a cell and/or rate of survival of a 7
cell according to clinically acceptable standards for the disorder to be 8
treated or the cosmetic purpose. 9
10
The ʼ076 application also states (Paper 322, page 9, citing Ex. 1018, col. 38:9-12 11
and col. 34:27-33) (emphasis added): 12
For instance, the subject compounds can be utilized to cause such 13
transformed cells to become either post-mitotic or apoptotic. 14
15
and 16
17
One aspect of the present invention relates to a method of 18
modulating a differentiated state, survival, and/or proliferation of a 19
cell, such as a normal cell or a cell having a … hedgehog gain-of-20
function, or smoothened gain-of-function, by contacting the cells with 21
a compound as set forth above according to the subject method and as 22
the circumstances may warrant. 23

According to Beachy, Tas’ real argument is that the ʼ076 application does not have 24
a sufficient number of “working examples” such that one skilled in the art would have 25
considered Beachy to be in possession of the subject matter of Count 3. Paper 322, 26
page 9:14-18. 27
Interferences 105,926 & 105,949

24

We find that Tas has not established that a working example is necessary to 1
adequately describe and enable an embodiment within the scope of Count 3. Ariad 2
Pharmaceuticals, Inc. v. Eli Lilly and Co., 598 F.3d 1336, 1352 (Fed. Cir. 2010): 3
There are, however, a few broad principles that hold true across 4
all cases. We have made clear that the written description 5
requirement does not demand either examples or an actual reduction 6
to practice; a constructive reduction to practice that in a definite way 7
identifies the claimed invention can satisfy the written description 8
requirement. 9

See also Falkner v. Inglis, 448 F.3d 1357, 1366 (Fed. Cir. 2006) (“the absence of 10
examples involving poxviruses in the Inglis applications does not render the written 11
description inadequate”). 12
Beachy understands Tas to assert that the contemporaneous art “taught away” from 13
the use of cyclopamine in humans. Paper 322, page 10. 14
Dr. Tas is said to have written Dr. William Gaffield in 2000 to obtain cyclopamine 15
for the experiments described in the Tas involved patent. Ex. 2098, ¶ 5:18 et seq.; 16
Ex. 1114, ¶ 57:22-23. 17
Dr. Gaffield is listed as a co-author of a 1999 paper entitled A Looking Glass 18
Perspective: Thalidomide and Cyclopamine, in CELL AND MOLECULAR BIOLOGY, 19
discussing the use of cyclopamine as a potential “lead compound in drug development” 20
for human therapeutics. Ex. 1112, pages 581-586 and in particular Abstract (page 579) 21
and Table 1 (page 584). See also Ex. 1114, ¶¶ 55-56 (Second Declaration of Thomas 22
Curran—a witness for Beachy). 23
Dr. Tas also testified that he was familiar with an article published in NATURE 24
entitled Effects of oncogenic mutations in Smoothened and Patched can be reversed by 25
Interferences 105,926 & 105,949

25

cyclopamine (listing Dr. Jussi Taipale as co-author) and which describes the use 1
of cyclopamine as a potential therapeutic agent for the treatment of basal cell 2
carcinoma tumors. Ex. 2098, page 8, ll. 8-9 and page 18, ll. 3-10; Ex. 2035, Abstract and 3
page 1007, Figs. 3c and 3d). 4
The Taipale et al. article describes the desirability of using therapeutic agents that 5
primarily affect pathways active during embryonic development, but not required for 6
survival in adults. Ex. 2035, page 1005, col. 1). 7
Beachy argues that, contrary to Tas’ argument, Taipale et al. did not teach that the 8
administration of cyclopamine to humans for the treatment of BCC would jeopardize 9
“vital functions” that were “critical to the survival” of the adult. Paper 322, page 15:2-5. 10
Beachy points to a brief review by Dr. Carol Wicking et al. entitled The role of 11
Hedgehog signaling in tumorigenesis, accepted for publication on 5 July 2001 in CANCER 12
LETTERS (Ex. 1041) just days after Tas filed his application on 2 July 2001 (Ex. 2004). 13
Paper 322, page 15. 14
CANCER LETTERS notes that “[o]ne agent which has arisen as a possible treatment 15
for BCCs is . . . cyclopamine.” Ex. 1041, page 4, col. 2 (¶ identified as “4. Possible 16
therapies for hedgehog-related BCCs”). 17
Beachy argues that the teachings of these prior and contemporary art references 18
reflect the beliefs of those skilled in the art that cyclopamine could be considered as a 19
viable therapeutic agent for treating BCC tumors in humans. Paper 322, page 15. 20
Beachy further argues that portions of Tas Motion 4 are not consistent with a 21
position taken by Tas in an amendment seeking to overcome the prior art. Paper 322, 22
pages 16-17. 23
Interferences 105,926 & 105,949

26

According to counsel for Tas (lead counsel in these interferences), “a 1
skilled artisan would have been motivated to administer a Hedgehog antagonist to a 2
patient having such a tumor with expectation of achieving inhibition of tumor 3
cell proliferation and inhibition of tumor growth.” Amendment; Ex. 2071, page 8:9-11. 4
Whether an application contains an adequate written description is an issue of fact. 5
In re Alton, 76 F.3d 1168, 1171 (Fed. Cir. 1996). To satisfy the written description 6
requirement of § 112, the disclosure of an application must reasonably convey to a skilled 7
artisan that the inventor had possession of the claimed subject matter as of the filing date. 8
Ariad, 598 F.3d at 1351 (citing Vas–Cath Inc. v. Mahurkar, 935 F.2d 1555, 1562–63 9
(Fed.Cir.1991)). 10
“[T]he specification [also] must [1] describe an invention understandable to that 11
skilled artisan and [2] show that the inventor actually invented the invention claimed.” 12
Ariad, 598 F.3d at 1351. 13
Whether an application contains an enabling disclosure is a question of law. In re 14
Wands, 858 F.2d 731, 735 (Fed. Cir. 1988). To satisfy the enablement requirement of 15
§ 112, the specification must enable one of ordinary skill in the art to practice the claimed 16
invention. Id. 17
Enablement is not precluded by the necessity for some experimentation. Id. 18
However, experimentation needed to practice an invention must not be undue 19
experimentation. Id. at 737. 20
Whether undue experimentation would have been required to make and use an 21
invention is a question of law to be resolved on the basis of the underlying facts. Enzo 22
Biochem, Inc. v. Calgene, Inc., 188 F.3d 1362, 1369 (Fed. Cir. 1999); Warner–Lambert 23
Co. v. Teva Pharm. USA, Inc., 418 F.3d 1326, 1337 (Fed. Cir. 2005). 24
Interferences 105,926 & 105,949

27

On the record before us, we agree with Beachy that furnishing an “example” is not 1
necessary. See Ariad, 598 F.3d at 1352. 2
We find that the “taught away” argument made by Tas is not convincing. 3
We further find that the quotations of ‘076 application set out above would 4
reasonably convey to one skilled in the art that the Beachy inventors had possession of 5
the subject matter of Count 3 as of the relevant filing date. 6
Beachy explicitly teaches: “the subject method can be used in the treatment of 7
human cancers, particularly basal cell carcinomas and other tumors of epithelial tissues 8
such as the skin” Ex. 1018, col. 48:16-22. 9
The ’076 application also describes (1) methods by which cyclopamine may be 10
administered, (2) appropriate dosages, and (3) how the subject medicament works within 11
the cancerous cell. 12
We find that Tas has not established that the ’076 application fails to satisfy the 13
written description requirement of § 112 with respect to disputed Limitation (1). 14
We conclude, in view of the portions of the ʼ076 application set out above, that Tas 15
has failed to establish that the ’076 application is not enabling as to the subject matter of 16
Count 3. 17
Nor has Tas sustained its burden of showing that undue experimentation would 18
have been needed to practice the invention defined by Count 3. 19
The ’076 application describes (1) effective dosages, (2) methods of 20
administration, and (3) a spectrum of conditions against which administration of the 21
cyclopamine may be effective as BCC cells. 22
23
24
Interferences 105,926 & 105,949

28

Motion 4, Limitation (2) 1
Wherein Hedgehog/Smoothened signaling is 2
utilized for inhibition of apoptosis 3

Tas maintains that Beachy has no support for disputed Limitation (2). Paper 197, 4
page 23:17-19 and page 24:1. 5
Tas argues that Beachy offers mostly vague statements as written description 6
support of the limitation “Hedgehog/Smoothed signaling is utilized for inhibition of 7
apoptosis” in a tumor cell. Id. at page 25:9-10 (relying on (1) Ex. 2030—a preliminary 8
amendment—and (2) Ex. 2098, ¶¶ 56-67—testimony of Dr. Tas). 9
Tas argues that Beachy’s proofs have no relevance to a tumor class in which Hh 10
signaling is used for inhibition of apoptosis. Id. at page 25:12-13. 11
According to Tas, the phrases inhibiting “[S]moothened-dependent pathway 12
activation” and “counteract the phenotypic effects of unwanted activation of a hedgehog 13
pathway” say nothing about a pathway that inhibits apoptosis of tumor cells. Id. 14
at 25:13-15. 15
Tas further argues that Beachy provides no basis for its contention that induction of 16
apoptosis would not also induce apoptosis in normal cells. Id. at page 26:2-3. 17
Tas contends that this lack of support becomes relevant when considering that the 18
only tumors to which Beachy administered cyclopamine have normal cells making up to 19
more than half of all of the cells. Id. at 26:3-6. 20
Beachy responds that BCC tumor cells are tumor cells in which smoothened-21
dependent hedgehog signaling is utilized for inhibition of apoptosis, i.e., that this is an 22
inherent property of BCC tumor cells regardless of whether an Hh inhibitor is 23
administered to the BCC tumor. Paper 322, page 20:13-14. 24
Interferences 105,926 & 105,949

29

Otherwise, the administration of a hedgehog inhibitor, such as cyclopamine, to a 1
BCC tumor would not result in inhibiting Smoothened-dependent Hh signaling to induce 2
apoptosis of BCC tumor cells. Id. at page 20:16-19 (citing Ex. 1088, ¶¶ 23-28 and 3
51-59—First Declaration of Dr. Thomas Curran). 4
Dr. Curran testified that as of 2000-2001, a person having ordinary skill in the art 5
would have expected “that inactivation of the Hh pathway in BCCs would result in 6
increased levels of apoptosis.” Ex. 1088, ¶ 25:5-7. 7
Dr. Curran further testified that “it is now well-established that the administration 8
of cyclopamine in amounts sufficient to inhibit the Hh pathway … results in an increase 9
in apoptosis.” Ex. 1088, ¶ 26:11-13 (emphasis in original). 10
Dr. Curran’s testimony is supported by contemporary scientific literature discussed 11
in paragraphs 27-32 of his testimony. 12
We find Dr. Curran’s testimony credible. 13
On the other hand, Tas does not point to any credible evidence to contradict 14
Dr. Curran’s testimony. 15
We decline to give much weight to Tas’ arguments with respect to its own 16
invention, or whether induction of apoptosis in BCC tumor cells would also involve 17
normal cells, with respect to the issue of whether the ʼ076 application fails to meet the 18
written description or enablement requirements of § 112. 19
To the extent that there is a conflict between the testimony given by disinterested 20
witness Dr. Curran (Ex. 1088) and that given by interested witness Dr. Tas (Ex. 2098), 21
we credit Dr. Curran’s testimony over Dr. Tas’ testimony. 22
Dr. Curran’s testimony is consistent with disclosure in the ’076 application. 23
Interferences 105,926 & 105,949

30

The ʼ076 application discloses that “the subject method can be used in treating or 1
preventing basal cell carcinoma or other hedgehog pathway-related disorders.” Ex. 1018, 2
col. 8:31-33. 3
Consequently, we find that Tas has not met is burden of demonstrating that the 4
ʼ076 fails to meet the written description and conclude that Tas has not met its burden of 5
establishing non-enablement of disputed Limitation (2). 6
7
Motion 4 Limitation (3) 8
Comprising administering to the human subject 9
a medicament comprising cyclopamine or 10
a pharmaceutically acceptable salt thereof 11

Tas argues that, when viewed in light of the prior art, a skilled person would have 12
had strong reasons to believe that it would not be feasible to administer cyclopamine or 13
another selective inhibitor of Hh/Smo signaling to a human with BCC for therapeutic 14
benefit. Paper 197, page 26. 15
According to Tas, neither the ʼ076 application nor any another Beachy publication 16
published prior to 2 July 2001 provides any reason for a person of ordinary skill to 17
believe that cyclopamine would feasibly be applicable to a tumor patient, let alone be 18
therapeutically successful. Id. 19
Therefore, Beachy is said to fail to satisfy the written description and enablement 20
of this limitation. 21
We have related supra our reasoning as to why the evidence adduced by Beachy 22
convincingly contradicts Tas’ “teaching away” argument, and we repeat that reasoning 23
here. 24
Interferences 105,926 & 105,949

31

Moreover, we have also related supra that we find that Beachy explicitly teaches 1
the administration of cyclopamine or a pharmaceutically acceptable salt thereof to a 2
human subject. 3
Consequently we find that Tas has not met is burden of demonstrating that the 4
Beachy application does not meet the written description and enablement requirements of 5
§ 112 as to disputed Limitation (3). 6
7
Motion 4, Limitation (4) 8
Wherein said medicament is administered in a dose 9
that is sufficient to induce apoptosis of said tumor cells 10

Tas argues that neither the Beachy Specification, nor any other Beachy publication 11
prior to Tas’ application, describes administration of cyclopamine, or other selective 12
inhibitor of Hh/Smo signaling, that successfully induced apoptosis of tumor cells. 13
Paper 197, page 27:1-4. 14
According to Tas, a skilled person reading the Beachy Specification, as well as the 15
prior art at the time of invention, would believe that the prior art taught against such a 16
dose. Id. at page 27:5. 17
Tas contends that such a skilled person would not learn from the disclosures of the 18
ʼ076 application that a dose of cyclopamine could cause a decrease of survival of cells. 19
Id. at page 27:9-10. 20
Tas further contends that the ʼ076 application does not disclose that apoptosis of 21
tumor cells will be induced by the administration of cyclopamine. Id. at page 27:11-12. 22
Tas still further contends that the ʼ076 application does not specify a dose that will 23
induce apoptosis in BCC tumor cells. Id. at page 27:12. 24
Interferences 105,926 & 105,949

32

For these reasons, Tas argues that the ʼ076 application fails to provide adequate 1
written description support and enablement to Count 3. 2
With respect to “effective dose”, the ʼ076 application states: 3
An “effective amount” of a subject compound, with respect to the 4
subject method of treatment, refers to an amount of the antagonist in a 5
preparation which, when applied as part of a desired dosage regimen 6
brings about, e.g., a change in the rate of cell proliferation and/or the 7
state of differentiation of a cell and/or rate of survival of a cell 8
according to clinically acceptable standards for the disorder to be 9
treated or the cosmetic purpose. 10
11
and 12
For instance, the subject compounds can be utilized to cause such 13
transformed cells to become either post-mitotic or apoptotic. 14

Ex. 1018, col. 10:8-15 and col. 38: 9-12. 15
Based on the dose disclosure of the ʼ076 application, we hold that Tas has not met 16
its burden of demonstrating that the ʼ076 application fails to meet the written description 17
and enablement requirements of § 112 as to disputed Limitation (4). 18

Interferences 105,926 & 105,949

33

Motion 4, Limitation (5) 1
And causes decrease of size or disappearance of the tumor 2
Tas argues that a skilled person reading Example 3 of the ʼ076 application 3
describing experiments with nude mice would not see evidence of the causation of the 4
decrease in size of even a tumor graft. Paper 197, Motion 4, page 28 (citing Ex. 1018, 5
col. 133:55 to col. 135:3). 6
According to Tas, the nude mice employed in the study have large proportions of 7
normal host cells reacting to the foreign transformed cells, and that it was well known in 8
the prior art that an observed change of size of a graft of foreign cells following an 9
administration could be due to an effect on the normal host cells and would not occur 10
even in a mouse having a naturally occurring tumor. Tas Motion 4, Paper 197, page 29 11
(citing, but not explaining the significance of, Exs. 2019, 2020, 2045, 2069). 12
Further according to Tas, the ʼ076 application nude mice descriptions do not 13
amount to causation of a decrease in size of a tumor in a human. Id. 14
Beachy relies on the testimony of Dr. Curran: 15
If one of ordinary skill in the art were in possession of a method of 16
treating BBC tumors in humans that involved the administration of 17
sufficient amounts of cyclopamine to inhibit Hh signaling in the tumor 18
cells, to reduce proliferation of tumor cells, to induce apoptosis in 19
tumor cells … and to achieve inhibition of tumor growth, then one of 20
ordinary skill would have reasonably expected that the same method 21
would also result in a decrease in tumor size, especially taking into 22
account additional factors such as naturally occurring apoptosis in the 23
BCC tumor and sloughing of skin cells. To make an analogy: 24
imagine that the tumor is a water-filled container with a hole in it. 25
Water must continuously run to keep the container filled with water 26
since water will continuously drip out through the hole. If you turned 27
off the water, the water level in the container starts to drop due to the 28
Interferences 105,926 & 105,949

34

leak and eventually all of the water runs out. In this analogy, the 1
running water is cellular proliferation within the tumor, and the hole 2
in the container (allowing water to drop out) is, for example, apoptosis 3
that occurs naturally in the BCC tumor …. If the cellular proliferation 4
(running water) is shut off, e.g., through Hh signaling pathway 5
inhibition, the naturally occurring apoptosis in the BCC tumor will 6
continue (the water will continue to drip out of the container), and the 7
tumor size will shrink (the water will run out of the container, and 8
eventually the container will run dry). 9
10
Ex. 1114, ¶ 96). 11
We find Dr. Curran’s explanation credible and we accord it considerable weight. 12
Based on Dr. Curran’s testimony we conclude that Tas has not met its burden of 13
showing that the ’076 application fails to satisfy the requirements of § 112 with respect to 14
disputed Limitation (5). 15
16
“Carnival barking,” “Gambling on both sides,” and “plagiarism” 17
Tas argues that the Beachy Specification engages in “carnival barking” (i.e., 18
claiming that its invention can perform an impossibly wide spectrum of effects), 19
“gambling on both sides” (i.e., the treatments are so varied and expansive the inventors 20
cannot actually have conceived what the compounds will do beyond those limited 21
experiments reported in their examples”). Paper197, pages 18-21. 22
We have related supra our reasoning with respect to how the Beachy Specification 23
satisfies the written description requirement with respect to each of the disputed 24
limitations of Count 3. 25
Moreover, Tas cites no legal authority to suggest that any of these arguments are at 26
all relevant to a § 112 analysis, nor can we find any such authority. 27
Interferences 105,926 & 105,949

35

Because none of these arguments are actually relevant to the analysis of whether 1
the Specification meets the written description or enablement requirements of § 112, we 2
find them to be without merit. 3
Because Tas has failed to meet its burden of demonstrating that the 4
’076 application is unpatentable under 35 U.S.C. § 112, Tas’ Motion 4 will be denied. 5
6
V. Tas Motion 6—lack of written description and indefiniteness
13
7
A. Tas motion 8
Tas moves for entry of judgment as to Beachy Claims 101-112 and 114-127 of 9
involved Beachy application 13/364,934 (Interference 105,926) and Beachy Claims 10
201-213 of involved Beachy application 13/364,121 (Interference 105,949) based on 11
(1) lack of a written description and (2) indefiniteness. Paper 198, page 1. 12
Beachy has opposed. Paper 323.
14
13
Tas has replied. Paper 331. 14
15

13
Tas Motion 6 is a combination of authorized Tas Motions 6, 13, 15 and 16.

14
Beachy characterizes its opposition as one “Regarding Beachy Written Description
and Enablement.” Paper 323, page 1. We believe Beachy intended to refer to
“Indefiniteness” rather than “Enablement.” Tas was not authorized to file a motion for
judgment based on an alleged lack of enablement.

Interferences 105,926 & 105,949

36

B. Lack of Written Description 1
Motion 6, Limitation (1) 2
“Treatment of a human having a tumor” 3
Beachy Claims 101-112, 114-127, and 201-213 4
Many of the arguments presented on behalf of Tas in connection with 5
Tas Motion 6 are the same as those advanced in connection with Tas Motion 4. 6
Tas argues that the Beachy applications fail to describe the treatment of a human 7
having any tumor or an animal having a naturally-occurring tumor, as a means of 8
disclosing to a person of ordinary skill that the treatment will be therapeutically effective 9
in a human. Paper 198, Motion 6, page 23:15-17. 10
Tas argues that the Beachy applications’ descriptions that tumor treatment will be 11
effective in tumor-bearing human would not lead a skilled person, familiar with the prior 12
art, to conclude that such treatment would likely be applicable, let alone effective. Id. at 13
page 23:17-20. 14
Tas further argues that when the Beachy applications were filed, the contemporary 15
art did not teach treatment of a human using cyclopamine sufficiently to satisfy a skilled 16
person that their treatment will be applicable or effective in human. Id. at page 23:20 to 17
page 24:3. 18
Tas still further argues that, as of the filing dates, the only treatments that had been 19
done were performed on tumor cells in culture and in nude mice having foreign tumor 20
cell grafts. Id. at page 24:3-6. 21
According to Tas, the results of these treatments taught away from a use inducing 22
apoptosis of tumor cells in a human. Id. at page 24:6. 23
Interferences 105,926 & 105,949

37

Tas contends that prior to its own filing there were substantial reasons to believe 1
that a human could not be effectively treated with cyclopamine to achieve any therapeutic 2
benefit. Id. at page 24:9-11. 3
Beachy argues that the involved Beachy applications describe the treatment of 4
tumors in humans. Paper 323, page 13:3-5. 5
For example, in support of its argument Beachy relies on the following. 6
In still another embodiment, the subject method can be used in the 7
treatment of human cancers, particularly basal cell carcinomas and other 8
tumors of epithelial tissues such as the skin. For example, subject 9
compounds can be employed, in the subject method, as part of a treatment 10
for basal cell nevus syndrome (BCNS), and other . . . human carcinomas, 11
adenocarcinomas, sarcomas and the like. 12
13
Ex. 1018, col. 48:16-22 (Beachy application 09/688,076 now US Patent 7,098,196 B1); 14
Ex. 1013, p. 63, ll. 24-28 (Beachy application 09/685,244) (italics added). 15
These compounds may be administered to humans and other 16
animals for therapy by any suitable route of administration, including 17
orally, nasally, as by, for example, a spray, rectally, intravaginally, 18
parenterally, intracisternally and topically, as by powders, ointments 19
or drops, including buccally and sublingually. 20
21
Ex. 1018, col. 50:13-18; Ex. 1013, p. 66:18-21 (italics added). 22
Whatever the mechanism, such inhibitors may have utility in 23
treament [sic] of disorders caused by inappropriate [Hh] pathway 24
activation. Patients with Basal Cell Nevus Syndrome (also termed 25
Gorlin's syndrome), an autosomal dominant disorder associated with 26
heterozygous loss-of function mutations in the human Ptc1 gene, 27
display increased incidence of numerous tumors, most notably basal 28
cell carcinoma (BCC), medulloblastoma, rhabdomyosarcoma and 29
fibrosarcoma. Loss-of-function mutations in Ptc1 or activating 30
mutations in Smo in addition are found in ~40% of sporadic BCC and 31
Interferences 105,926 & 105,949

38

~25% of primitive neuroectodermal tumors. The ability of 1
cyclopamine and its derivatives to block pathway activation by both 2
of these types of mutations suggests that these plant-derived 3
compounds or others that influence the activity of Smo may be 4
valuable as therapeutic agents. 5
6
Ex. 1018, col. 66:3-19 (italics added). 7
An “effective amount” of a subject compound, with respect to the 8
subject method of treatment, refers to an amount of the antagonist in a 9
preparation which, when applied as part of a desired dosage regimen 10
brings about, e.g., a change in the rate of cell proliferation and/or the 11
state of differentiation of a cell and/or rate of survival of a cell 12
according to clinically acceptable standards for the disorder to be 13
treated or the cosmetic purpose. 14
15
Ex. 1018, col. 10:8-15; Ex. 1013, page 17:16-21. 16
17
For instance, the subject compounds can be utilized to cause such 18
transformed cells to become either post-mitotic or apoptotic. 19
20
Ex. 1018, col. 38:9-12; Ex. 1013, page 49:7-8. 21
The subject smoothened antagonists may also be used to inhibit 22
proliferation (or other biological consequences) in cells or tissues 23
characterized as having a patched loss-of-function phenotype, a 24
smoothened gain-of-function phenotype or a hedgehog gain-of- 25
function phenotype. 26
27
Ex. 1018, col. 7:55-60; Ex. 1013, page 14:18-22. 28
Beachy repeats its argument (made in Beachy Opposition 4) that its applications 29
need not provide working examples of human experiments to satisfy the written 30
description requirements of 35 U.S.C. § 112. Paper 323, page 14:31 to page 15. 31
Interferences 105,926 & 105,949

39

Beachy also repeats its arguments (made in Beachy Opposition 4) with respect to 1
Tas’ “teaching away” arguments; viz., that the teachings of the contemporary art would 2
not have caused a person of ordinary skill in the art to expect that a human could not be 3
effectively treated with cyclopamine to achieve any therapeutic benefit. Id. at page 15:16 4
to page 17:14. 5
In our decision with respect to Motion 4, we state why we agree with Beachy’s 6
arguments. 7
For the same reasons we are not persuaded with respect to these same arguments in 8
connection with Tas Motion 6. 9
Tas has not met its burden of showing that the Beachy Specifications fail to satisfy 10
the requirements of § 112 with respect to disputed Limitation (1). 11
12
Motion 6, Limitation (2) 13
Smoothened-dependent hedgehog signaling 14
is utilized for inhibition of apoptosis 15
(Claims 101-112, 114, 117-127, 201-213) 16
Tas repeats its argument made with respect to the corresponding limitation of 17
Count 3 in Tas Motion 4. Paper 198, page 24:12 to 26:8. 18
We have discussed why we are not convinced by these same arguments with 19
respect to Tas Motion 4. 20
For the same reasons, we are similarly not convinced with respect to the same 21
arguments with respect to Tas Motion 6. 22
Tas has not met its burden of showing that the Beachy Specifications fail to satisfy 23
the requirements of § 112 with respect to disputed Limitation (2). 24
25
Interferences 105,926 & 105,949

40

Motion 6, Limitation (3) 1
Determining that smoothened-dependent hedgehog signaling 2
is utilized for inhibition of apoptosis in said tumor 3
(Claims 115-116) 4
Tas essentially repeats the arguments that it employed with respect to Motion 4, 5
Limitation (2). Paper 198, page 24:12 to page 26:8. 6
We have discussed why we are not persuaded by those arguments in connection 7
with our decision on Tas Motion 4. 8
For the same reasons, we are not convinced with respect to the same arguments 9
made in connection with Tas Motion 6. 10
Tas has not met its burden of showing that the Beachy Specifications fail to satisfy 11
the requirements of § 112 with respect to disputed Limitation (3). 12
Motion 6, Limitation (4) 13
Wherein said medicament is administered in a dose 14
that induces apoptosis in said tumor 15
(Claims 101-114, 126, 127, 201-213) 16
Tas relies upon essentially the same arguments that it made with respect to the 17
corresponding limitation of Count 3 in its Motion 4. Paper 198, Motion 6, page 26:14 to 18
page 28:16. 19
We have discussed why we are not persuaded by those arguments with respect to 20
Motion 4. 21
For the same reasons, we are not convinced with respect to the same arguments in 22
connection with Tas Motion 6. 23
Tas has not met its burden of showing that the Beachy Specifications fail to satisfy 24
the requirements of § 112 with respect to disputed Limitation (4). 25
Interferences 105,926 & 105,949

41

1
Motion 6, Limitation (5) 2
Said medicament is administered in a dose that is sufficient 3
to induce apoptosis of said tumor cells 4
(Claims 115-116) 5
Tas essentially repeats the arguments that it employed in connection with 6
Motion 4. Paper 198, page 28:6-16. 7
We have discussed why we are not persuaded by those arguments in connection 8
with Motion 4. 9
For the same reasons, we are not persuaded with respect to the same arguments in 10
connection with Tas Motion 6. 11
Tas has not met its burden of showing that the Beachy Specifications fail to satisfy 12
the requirements of § 112 with respect to disputed Limitation (5). 13
14
Motion 6, Limitation (6) 15
A tumor in which smoothened-dependent hedgehog signaling 16
is used for inhibition of apoptosis and … administering 17
to the subject an effective amount of medicament 18
(Claims 117-125) 19
Tas essentially repeats the arguments that it made in connection with Motion 6, 20
Limitations (2) to (5). Paper 198, page 28:17-22. 21
Because we were not persuaded by Tas’ arguments with respect to those 22
limitations, we are likewise not persuaded by Tas’ arguments with respect to this 23
limitation. 24
Tas has not met its burden of showing that the Beachy Specifications fail to satisfy 25
the requirements of § 112 with respect to disputed Limitation (6). 26
Interferences 105,926 & 105,949

42

Motion 6, Limitation (7) 1
Causes decrease of size of the tumor 2
(Claims 101-112, 114-127) 3
Tas essentially relies on the same arguments that it made with respect to the 4
corresponding limitation of Count 3. Paper 198, page 28:23 to page 29:9. 5
We have discussed why we are not persuaded by those arguments with respect to 6
Motion 4. 7
For the same reasons, we are not persuaded with respect to the same arguments in 8
connection with Tas Motion 6. 9
Tas has not met its burden of showing that the Beachy Specifications fail to satisfy 10
the requirements of § 112 with respect to disputed Limitation (7). 11
12
Motion 6, Limitation (8) 13
Smoothened-dependent hedgehog signaling is used for inhibition 14
(or selective inhibition) of differentiation 15
(Claims 103, 105, 106-111, 117-125, 202-211) 16
and 17
said dose is sufficient to induce differentiation in said tumor 18
(Claims 103,105-111) 19
Tas argues that the Beachy Specifications do not disclose to a person of ordinary 20
skill that Smo-dependent Hh signaling is used for inhibition of differentiation. 21
Paper 198, page 29:14-15. 22
According to Tas, Ex. 1009 (Beachy US Patent 7,291,626 B1) discloses that Hh 23
signaling induces differentiation of cells. Id. (citing, e.g., Ex. 1009, col 7: 28-29 and 24
col. 8:31-34). 25
Interferences 105,926 & 105,949

43

By contrast, Tas argues that Ex. 1018 (Beachy US Patent 7,098,196 B1) discloses 1
a greater degree of differentiation in tumor grafts in cyclopamine- or KAAD-2
cyclopamine-injected nude mice, relative to the tomatidine-injected mice. Id. at 3
page 29:14-21. 4
However, Tas contends that a person of ordinary skill in the art would have known 5
that subcutaneous injection of foreign tumor cells into nude mice commonly induces 6
varying differentiation of tumor cells by itself, in the absence of administration of a drug. 7
Id. at page 29, l. 21 to page 30, l. 10; see also p. 11, ll. 1-5 (citing Ex. 2043
15
and 8
Ex. 2044
16
). 9
Tas also argues that it was recognized in the contemporary art that, due to a 10
variable—but significant residual immune response of nude mice against the 11
subcutaneously injected foreign tumor cells—a person of ordinary skill would have 12
known that it was necessary to determine that an observed treatment effect on 13
differentiation of the grafted tumor cells was not due to an effect on the normal host cells. 14
Paper 198, page 30:6-10 (citing, e.g., Ex. 2043—Boukamp, n.15). 15
Beachy argues that one of ordinary skill in the art would have understood that the 16
observed decrease in proliferation was attributable to cyclopamine inhibiting the Hh 17
pathway, which would also result in inducement of apoptosis (due to, for example, lower 18
levels of Bcl-2 protein) and increased differentiation of tumor cells. Paper 323, 19

15
Boukamp et al., Environmental Modulation of the Expression of Differentiation and
Malignancy in Six Human Squamous Cell Carcinoma Cell Lines, 45 CANCER RESEARCH
5582 (1985).

16
Helson et al., Human Neuroblastoma in Nude Mice, 35 CANCER RESEARCH 2594
(1975).

Interferences 105,926 & 105,949

44

page 5:18 to page 6:2 (citing Ex. 1025
17
; Ex. 1027
18
; Ex. 1088, ¶¶ 24- 35 (First Curran 1
declaration); Ex. 1114, ¶ 95 (Second Curran declaration). 2
We are persuaded by Beachy’s arguments. 3
In his second declaration, Dr. Thomas Curran quotes from the ’076 application: 4
An “effective amount” of a subject compound, with respect to the 5
subject method of treatment, refers to an amount of the antagonist in a 6
preparation which, when applied as part of a desired dosage regimen brings 7
about, e.g., a change in the rate of cell proliferation and/or the state of 8
differentiation of a cell and/or rate of survival of a cell according to 9
clinically acceptable standards for the disorder to be treated or the cosmetic 10
purpose. 11
12
Ex. 1114, ¶ 94 (quoting Ex. 1018, col. 10:8-15) (italics added). 13
Dr. Curran further quotes from the disclosure of the ’076 application: 14
One aspect of the present invention relates to a method of 15
modulating a differentiated state, survival, and/or proliferation of a 16
cell, such as a normal cell or a cell having a ptc loss-of-function, 17
hedgehog gain-of-function, or smoothened gain-of-function, by 18
contacting the cells with a compound as set forth above according to 19
the subject method and as the circumstances may warrant. 20
21
Ex. 1114, ¶ 94 (quoting Ex. 1018, col. 34:27-33). 22
Dr. Curran was of the opinion that “Beachy also specifically teaches that the 23
subject compounds, such as cyclopamine, could be administered in doses sufficient to 24

17
Fan et al., Induction of basal cell carcinoma features in transgenic human skin
expressing Sonic Hedgehog, 3 NATURAL MEDICINE 788 (1997).

18
Fan et al., Sonic Hedgehog Opposes Epithelial Cell Cycle Arrest, 147 J. OF CELL
BIOLOGY 71 (1999)

Interferences 105,926 & 105,949

45

induce various biological effects, including apoptosis [and differentiation].” Ex. 1114, 1
¶ 94. 2
Accordingly, Dr. Curran reasoned that one of ordinary skill in the art would have 3
recognized the above-identified statement as consistent with the fact that (1) aberrant 4
activation of the Hh pathway in BCC tumors results in increased levels of Bcl-2 and, 5
therefore (2) inhibition of the pathway would result in decreased levels of Bcl-2 protein 6
and, (3) hence, increased levels of apoptosis [and differentiation].” Ex. 1114, ¶ 95. 7
We are persuaded by Beachy’s arguments and proofs. The ’076 application 8
discloses that: 9
The subject compounds may be formulated as a pharmaceutical 10
preparation comprising a pharmaceutically acceptable excipient. 11
Smoothened antagonists of the invention and/or preparations 12
comprising them may be administered to a patient to treat conditions 13
involving unwanted cell proliferation, e.g., cancer and/or tumors (such 14
as medulloblastoma, basal cell carcinoma, etc.), non-malignant 15
hyperproliferative disorders, etc. Smoothened agonists can also be 16
used to regulate the growth and differentiation of normal tissues. In 17
certain embodiments, such compounds or preparations are 18
administered systemically and/or locally, e.g., topically. 19
20
Ex. 1018, col. 7:1-12 (italics added). Furthermore, Ex. 1027 (Fan et al., supra n.18) 21
discloses that: “Cell cycle exit before outward migration and terminal differentiation is a 22
cardinal feature of normal stratified epithelium. Here we report that [Hh] inhibits this 23
process” and that “[o]ur findings indicate that [Hh] action promotes cellular proliferation 24
by opposing cell cycle arrest [and the subsequent differentiation]. Ex. 1027, page 74, 25
col. 1 (under Discussion) and page 75, col. 2, last ¶; see also Ex. 1088, ¶ 28 (First Curran 26
declaration). 27
Interferences 105,926 & 105,949

46

The literature supports, and is consistent with, Dr. Curran’s statement that one of 1
ordinary skill in the art would have appreciated that that aberrant activation of the Hh 2
pathway in BCC tumors resulted in increased levels of Bcl-2 and, therefore, inhibition of 3
the pathway would result in decreased levels of Bcl-2 and, hence, increased levels of 4
apoptosis and differentiation. Ex. 1114, ¶ 95. 5
Based on Dr. Curran’s testimony, we are not persuaded by Tas’ conjecture that the 6
differentiation of injected tumor cells is merely a confounding experimental artifact. 7
Tas has not met its burden of showing that the Beachy Specifications fail to satisfy 8
the requirements of § 112 with respect to disputed Limitation (8). 9
10
Motion 6, Limitation (9) 11
Wherein said amount of cyclopamine is not toxic to 12
the subject and causes reduced side effects 13
(Claims 104-105; 203) 14
Tas asserts that the Beachy applications lack any description of a human being 15
administered cyclopamine and also that it lacks any description of the induction of tumor 16
cell apoptosis in any species. Paper 198, Motion 6, page 30:11-17. 17
As a result, Tas maintains that the Beachy applications lack written description 18
demonstrating no toxicity or reduced side effects of cyclopamine in humans. Id. 19
Beachy responds by noting that the written description requirement of § 112 does 20
not require actual examples of human administration of cyclopamine. Paper 323, 21
page 29:5-6. 22
Beachy further responds to Tas’ argument that the Beachy Specifications “have no 23
description of apoptosis and, therefore, no description of no toxicity or reduced side 24
Interferences 105,926 & 105,949

47

effects” with the argument that it made with respect to the corresponding limitations in 1
Motion 3. Id. at page 29. 2
Beachy still further responds by noting that in its earliest filings, Beachy described 3
hedgehog antagonists as often exerting cystostatic, rather than cytotoxic, effects on 4
epithelial cells, including hair follicle cells. Id. at page 29:11-14 (citing Ex. 1016, 5
page 43, second full ¶ (Beach Provisional Application 60/081,263); see also Ex. 1114, 6
¶¶ 67-68 (Second Curran Declaration). 7
We agree with Beachy. 8
We have discussed our reasoning with respect to why Beachy need not provide 9
examples of human experimentation to satisfy the written description requirement of 10
§ 112. 11
Moreover, Beachy’s 1998 Provisional Application recites: 12
Moreover, because a hedgehog antagonist will often be cytostatic to 13
epithelial cells, rather than cytotoxic, such agents can be used to protect hair 14
follicle cells from cytotoxic agents which require progression into S-phase 15
of the cell-cycle for efficacy, e.g. radiation-induced death. Treatment by the 16
subject method can provide protection by causing the hair follicle cells to 17
become quiescent, e.g., by inhibiting the cells from entering S phase, and 18
thereby preventing the follicle cells from undergoing mitotic catastrophe or 19
programmed cell death. 20
21
Ex. 1016, page 43, second full ¶. 22
Furthermore, in his Second Declaration, Dr. Curran testifies that: 23
Prior to the Tas filing, evidence had been published showing that a 24
Hedgehog antagonist, while inducing the regression of BCC-like 25
structures in a skin punch assay from an embryonic mouse model, had 26
no cytotoxic effect on normal skin cells as shown by their normal 27
histology. (See Ex. 1065, Baxter et al. WO 2001/26644, page 126, 28
line 23 - page 127, line 17). This work was subsequently published in 29
Interferences 105,926 & 105,949

48

Williams et al., Identification of a small molecule inhibitor of the 1
Hedgehog signaling pathway: Effects on basal cell carcinoma-like 2
lesions, PROC NATL ACAD SCI USA 100(8): 4616-21 (April 2003; 3
Ex. 1034). Note that compound D of Baxter et al. WO 2001/26644 4
(Ex. 1065) is the same compound as CUR-61414 of the Williams et 5
al. publication (Ex. 1034). One of ordinary skill in the art also knows 6
that, in most adult tissues, Hh pathway activity is present in many 7
fewer cellular sites than in the developing embryo, primarily 8
functioning in tissue maintenance and repair. (Ex. 1021, Scales et al., 9
Abstract; Ex. 2063, Lipinski RJ et al., Abstract). Therefore, one of 10
ordinary skill in the art would not have expected the administration of 11
a Hedgehog inhibitor to adversely selectively cause normal cells to 12
“succumb.” The involved Beachy ‘076 specification specifically 13
contemplates the effect (cytostatic rather than cytotoxic) of Hedgehog 14
inhibitors on hair follicle cells that have active Hedgehog signaling: 15

Moreover, because a subject compound will often be cytostatic 16
to epithelial cells, rather than cytotoxic, such agents can be used 17
to protect hair follicle cells from cytotoxic agents which require 18
progression into S-phase of the cell-cycle for efficacy, e.g. 19
radiation induced death. [Ex. 1018, Beachy ‘076 application, 20
col. 46, ll. 30-34]. 21
22
Ex. 1114, ¶ 67 (page 42:9 to page 43:13) (boldface added). 23
Based on Dr. Curran’s testimony, we find that a person of ordinary skill in the art 24
would have known at the time of Beachy’s filings, that Hh inhibitors are cytostatic rather 25
than cytotoxic, and consequently would have known that Beachy was in possession of 26
cyclopamine that was not toxic and reduced side effects. 27
Tas has not met its burden of demonstrating that disputed Limitation (9) fails the 28
written description requirement of § 112. 29
30
Interferences 105,926 & 105,949

49

Motion 6, Limitation (10) 1
Administering to the subject an effective amount 2
(or a therapeutically effective amount) of a medicament 3
comprising cyclopamine” 4
(Claims 117-125, 202-211) 5
and 6
inhibits tumor cell proliferation 7
(or inhibits proliferation of said tumor) 8
(Claims 201-205) 9
Tas argues that, prior to the Tas invention, a person of ordinary skill would believe 10
that the only expected benefit of administering a selective inhibitor of Hh/Smo signaling 11
to a human with a BCC tumor by administration would be reduced proliferation of tumor 12
cells resulting in reduced tumor growth. Paper 198, page 30:21-23. 13
According to Tas, a skilled artisan would have been warned against such an 14
administration for “multiple reasons.” 15
Tas argues (1) that proliferation and apoptosis of cells are regulated by different 16
mechanisms, (2) that the inhibition of tumor cell proliferation does not necessarily induce 17
apoptosis and (3) can, in fact, cause inhibition of apoptosis, depending on the particular 18
signals. Id. at page 31:4-7 (citing Ex. 2009
19
and references therein
20
). 19

19
Lipponen, Apoptosis in breast cancel: relationship with other pathological
parameters, 6 ENDORINE-RELATED CANCER 13 (1999).

20
We have not considered the “references therein”. See DeSilva v. DiLeonardi,
181 F.3d 865, 866-67 (7th Cir 1999) (a brief must make all arguments accessible to the
judges, rather than ask them to play archaeologist with the record; Halliburton Energy
Services, Inc. v. M-I LLC, 514 F.3d 1244, 1250 n.2 (Fed. Cir. 2008) (a skeletal argument,
really nothing more than an assertion, does not preserve a claim; Judges are not like pigs,
hunting for truffles buried in briefs, quoting United States v. Dunkel, 927 F.2d 955, 956
(7th Cir. 1991).
Interferences 105,926 & 105,949

50

Based on the foregoing, Tas argues that a reduced proliferation of tumor cells does 1
not provide written description of induction of apoptosis. Id. at page 31:9-11. 2
Beachy points out that none of Tas’ arguments presented with respect to this 3
limitation dispute that Beachy provides an adequate description of inhibiting proliferation 4
of tumor cells and inhibiting tumor growth. Paper 323, page 30:3-5. 5
This is significant, argues Beachy, because one of ordinary skill in the art would 6
have known that inhibition of the Hh pathway in a BCC tumor cell resulting in inhibition 7
of tumor growth would also induce apoptosis (through decreased levels of the Bcl-2 8
protein) and therefore cause a decrease in tumor size. Id. at page 30:6-10 (citing 9
Ex. 1088, ¶ 55; Ex. 1114, ¶ 95 (testimony of Dr. Curran)). 10
With respect to Tas’ contention that the background frequency of apoptosis in the 11
absence of treatment does not provide for their decrease of size and that proliferation and 12
apoptosis of cells are “regulated differently,” Beachy disagrees. 13
Beachy argues that, as the level of proliferating tumor cells decreases and the 14
apoptotic index increases (due to both induced and naturally-occurring apoptosis), one of 15
ordinary skill in the art would reasonably expect the tumor to decrease in size and/or 16
disappear because the cell loss caused by apoptosis would not be compensated by the 17
generation of new tumor cells by proliferation. Id. at page 30 (again citing Dr. Curran’s 18
testimony at Ex. 1088, ¶¶ 55; Ex. 1114, ¶ 95). 19
Furthermore, Beachy argues that one of ordinary skill in the art would have 20
understood that the observed decrease in proliferation was attributable to cyclopamine 21
inhibiting the Hh pathway, which would also result in inducement of apoptosis (due to 22

Interferences 105,926 & 105,949

51

lower levels of Bcl-2 protein) and increased differentiation of tumor cells. Id. at 1
page 30:20 to page 4 (citing Dr. Curran’s testimony at Ex. 1114, ¶ 95). 2
Beachy also disputes Tas’ statement that: “…and would not obtain an induction of 3
apoptosis of tumor cells that would cause decrease of size or disappearance of a tumor 4
(¶[¶] 14, 15, 18, 48-51).” Paper 323, page 31:11-13 (quoting Paper 198, page 31:3-4) 5
(emphasis by Beachy). 6
Beachy asserts that no such limitation appears in any Beachy claim, any Tas claim, 7
or either Count 2 or Count 3. Id. at page 31:13-14. 8
Rather, Beachy argues that the relevant Beachy claims recite administering a 9
sufficient dose of cyclopamine to (1) induce apoptosis and (2) cause a decrease of size or 10
disappearance of a tumor. Id. at page 31:14-16. 11
Beachy contends that one of ordinary skill in the art would understand that a tumor 12
can decrease in size after administration of cyclopamine for reasons other than apoptosis 13
of tumor cells, or for reasons in conjunction with apoptosis, e.g., reduction of tumor cell 14
proliferation, naturally-occurring apoptosis and sloughing off of epithelial cells. 15
Paper 323, page 31: 16-19 (citing Dr. Curran’s testimony at Ex. 1088, ¶¶ 51-57). 16
Tas’ arguments are not persuasive. 17
We find no credible factual support for Tas’ contention that: 18
[A] skilled person was however warned against such an 19
administration for multiple reasons and, if he or she had at al decided 20
to administer, would administer the lowest dose effective and would 21
not obtain an induction of apoptosis of tumor cells that would cause 22
decrease of size or disappearance of a tumor. 23
24
Paper 198, page 30:23 to page 31:4 25
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52

Moreover, Exhibit 2009,
21
Antti Sarastea and Kari Pulkkic, Morphologic and 1
biochemical hallmarks of apoptosis, 45 CARDIOVASCULAR RESEARCH 528–537 (2000), 2
provides a general review of “the current knowledge on the molecular mechanisms of 3
apoptosis as they relate to the morphologic hallmarks and their implications for the 4
detection of apoptosis in cardiac tissue”. 5
But Tas points to nothing in the reference, or the references contained therein, that 6
credibly supports its contention that “inhibition of tumor cell proliferation does not 7
induce their apoptosis and can, in fact, cause inhibition of apoptosis depending on the 8
particular signals.” Ex. 2009, Abstract (emphasis added); Paper 198, page 31:4-7. 9
In his First Declaration, Dr. Curran opines that: 10
[a] method of treating BCC tumors in humans by the administration of 11
cyclopamine in amounts sufficient to result in a decrease of proliferation of 12
BCC tumor cells would have taught or suggested a method to achieve 13
apoptosis and a decrease of size or disappearance of the BCC tumor. One of 14
ordinary skill in the art would have understood that the observed decrease in 15
proliferation was attributable to cyclopamine inhibiting the Hh pathway, 16
which would also result in inducement of apoptosis (due to lower levels of 17
Bcl-2 protein) and increased differentiation of tumor cells. As the level of 18
proliferating tumor cells decreases and the apoptotic index increases (due to 19
both induced and naturally-occurring apoptosis), one of ordinary skill in the 20
art would reasonably expect the tumor to decrease in size and/or disappear 21
because the cell loss caused by apoptosis would not be compensated by the 22
generation of new tumor cells by proliferation. 23
24
Ex. 1088, ¶ 55. 25
Dr. Curran further opined, in his Second Declaration, that: 26

21
Antti Sarastea et al., Morphologic and biochemical hallmarks of apoptosis,
45 CARDIOVASCULAR RESEARCH 528–537 (2000).

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53

one of ordinary skill in the art would have known that [Hh] induced 1
bcl-2 and thus potentially resists apoptosis (Ex. 1027, Fan et al. 1999) and 2
that bcl-2 is expressed in BCCs (Ex. 1025, Fan et al. 1997). Accordingly, 3
one of ordinary skill in the art would have recognized the above-identified 4
statement as consistent with the fact that aberrant activation of the Hh 5
pathway in BCC tumors resulted in increased levels of Bcl-2 and, therefore, 6
inhibition of the pathway would result in decreased levels of Bcl-2 and, 7
hence, increased levels of apoptosis. 8
9
Ex. 1114, ¶ 95 (see also Ex. 1088, ¶¶ 24-35). 10
We find that Dr. Curran’s characterization of the contemporary art at the time of 11
filing to be credible. 12
Dr. Curran testifies that it was known in the art (see, e.g., Exs. 1025, 1027) that 13
increased expression of Hh-induced Bcl-2 protein in BCC cells rendered those cells 14
resistant to apoptosis and that inhibition of Bcl-2 expression consequently decreased the 15
cells’ resistance to apoptosis. Ex. 1114, ¶ 95; Ex. 1088, ¶¶ 24-35. 16
Furthermore, we reject Tas’ argument that the language of the Beachy claims 17
requires that the induction of apoptosis directly causes the decrease in size or 18
disappearance of a tumor. 19
None of the language of the Beachy claims requires that causal link, as Beachy 20
successfully argues. 21
Rather, as Dr. Curran states: 22
One of ordinary skill in the art would have understood that the 23
observed decrease in proliferation was attributable to cyclopamine 24
inhibiting the Hh pathway, which would also result in inducement of 25
apoptosis (due to lower levels of Bcl-2 protein) and increased 26
differentiation of tumor cells. As the level of proliferating tumor cells 27
decreases and the apoptotic index increases (due to both induced and 28
naturally-occurring apoptosis), one of ordinary skill in the art would 29
Interferences 105,926 & 105,949

54

reasonably expect the tumor to decrease in size and/or disappear 1
because the cell loss caused by apoptosis would not be compensated 2
by the generation of new tumor cells by proliferation. 3
4
Ex. 1088, ¶ 55. 5
Tas’ position is not consistent with Dr. Curran’s credible testimony. 6
We accept Dr. Curran’s testimony that suppression of the Hh pathway by 7
cyclopamine resulting in decreased tumor cell proliferation was known in the art at the 8
time of invention. 9
Tas has not met its burden of demonstrating that disputed Limitation (10) fails the 10
written description requirement of § 112. 11
“Carnival barking,” “Gambling on both sides,” and “plagiarism” 12
We have discussed our reasoning with respect to these allegations in addressing 13
similar arguments made in connection with Tas Motion 4. 14
Tas cites no legal authority to suggest that any of these arguments are relevant to a 15
Section 112 analysis, nor are we aware of any such authority. 16
Because none of these arguments are related to an analysis of whether the 17
Specification meets the written description or enablement requirements of § 112, we find 18
them to be without merit. 19
20
C. Indefiniteness 21
Tas argues that the Beachy claims are unpatentable under 35 U.S.C. § 112 as 22
indefinite when read in light of the prior art. Paper 198, page 31. 23
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55

According to Tas, it is unclear from the claims whether Smo-dependent Hh 1
signaling is utilized for inhibition of apoptosis of normal cell types or of transformed 2
cells in the tumor. Id. at page 31:14-15 3
Further according to Tas, the only actual administration to a tumor-bearing subject 4
described in the Beachy applications is to a nude mouse having a graft of foreign 5
transformed cells. Id. at page 31:17-18. 6
Tas argues that it is well-known that an observed effect in such grafts can be due to 7
a primary effect on the normal host cells rather than to the transformed cells and would 8
not occur even in a mouse having a naturally occurring tumor, let alone in humans. Id. at 9
page 31:18 to page 32:1. 10
Tas further argues that the Beachy applications contain no description that would 11
show to the person of ordinary skill that Hh/Smo signaling is utilized for inhibition of 12
apoptosis of a cell type in a tumor. Tas further argues that the Beachy applications do not 13
disclose any dosage of cyclopamine for the induction of apoptosis of any cell type in any 14
tumor. Tas reasons, therefore, that person of ordinary skill would not have a reference to 15
rely upon to decide what is meant by “smoothened dependent Hedgehog signaling is 16
utilized for inhibition of apoptosis.” Id. at page 32:14-19. 17
Tas still further argues further that while Beachy claims 103, 105-11, 117-126, 18
202-211, and 213, Beachy’s Example 3 purports to disclose the induction of 19
differentiation, nevertheless a skilled person would discern no evidence of such 20
differentiation and would be unable to determine that an induction of differentiation is 21
caused by administration of cyclopamine. 22
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56

Tas next argues that the claim term “effective amount” cannot be reasonably 1
construed because the Beachy Specifications disclose no basis for the claimed 2
classification of tumors. Id. at page 33:8-14. 3
Tas also argues that it cannot be determined from the Beachy applications the 4
amount or dose that would be effective in producing the multiple claimed effects. Id. 5
at page 33:13-14. 6
Tas claims that it was unknown in prior art that cyclopamine or other selective 7
inhibitors of Smo-dependent Hh signaling can induce apoptosis of tumor cells and, 8
further, that it was unknown that different amounts or doses are required to produce 9
apoptosis and other effects. Id. at page 33:14-18. 10
Furthermore, argues Tas, a skilled person reading the Example 3 of the Beachy 11
applications, which describes the use of nude mice, would not know what an effective 12
amount would be to produce a given effect on normal cells or on transformed cells in a 13
tumor. Id. at page 33:17-19. 14
Beachy argues that Tas’ allegations regarding indefiniteness are irreparably 15
confused and entangled with its written description arguments (which, in turn, are 16
entangled with enablement arguments that are based on a misunderstanding of the 17
relevant prior art). Paper 323, page 35:8-11. 18
According to Beachy, Tas repeats arguments relating to the presence of working 19
examples in the Beachy Specifications’ disclosures, and concludes that one skilled in the 20
art would be unable to decide what is meant by the term “smoothened-dependent 21
Hedgehog signaling is utilized for inhibition of apoptosis.” Id. at page 34:18 to 22
page 35:2. 23
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57

“Whether a claim is [unpatentable] for indefiniteness requires a determination 1
whether those skilled in the art would understand what is claimed when the claim is read 2
in light of the specification.” Morton Int’l, Inc. v. Cardinal Chem. Co., 5 F.3d 1464, 3
1470 (Fed. Cir. 1993). 4
The party challenging indefiniteness in an interference bears the burden of proving 5
unpatentability by a preponderance of the evidence. Bruning v. Hirose, 161 F.3d 681, 6
685 (Fed. Cir. 1998) (the burden of proof on the issue of patentability of the claims of a 7
patent in an interference where applications are co-pending is by a preponderance of the 8
evidence); Bilstad v. Wakalopulos, 386 F.3d 1116, 1120 (Fed. Cir. 2004). 9
Tas Motion 6 does not articulate a coherent or convincing argument that a person 10
of ordinary skill would fail to understand what is claimed when the Beachy claims are 11
read in light of the specifications. 12
Tas relies on factually unsupported assertions as to what a skilled artisan might or 13
might not understand, in an attempt to poke holes in the experimental examples presented 14
in the Beachy applications, but adduces no direct credible evidence to indicate that the 15
claims, when viewed in light of the specifications, are indefinite. 16
Exhibits offered by Tas (e.g., Exs. 2019, 2020, 2045, 2072, 2073, 2098) are 17
generally directed to the properties of tumor cells in xenografts, but Tas adduces these 18
only to attack Example 3. 19
These arguments are irrelevant to an analysis of indefiniteness and Tas points to no 20
direct credible proof that a person of ordinary skill, having read the Specifications, would 21
fail to understand what is being claimed. 22
Tas thus fails to meet this burden, and we conclude that Tas has filed to establish 23
that the Beachy claims are unpatentable as indefinite under 35 U.S.C. § 112. 24
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58

D. Conclusion 1
Because Tas has failed to meet its burden of demonstrating that claims of 2
the Beach ’934 application and the Beach ’121 application are unpatentable under 3
35 U.S.C. § 112 for lack of written description or indefiniteness, Tas’ Motion 6 will be 4
denied. 5
6
VI. Tas Motion 14 7
Tas moves to designate Tas claims 1, 3, 5 and 23 as not corresponding to Counts 2 8
and 3. Paper 199, page 1. 9
Tas independent claim 1 recites: 10
1. A method for inducing apoptosis of tumor cells in a tumor-bearing 11
patient, comprising 12
13
determining that Hedgehog/Smoothened signaling is utilized for 14
inhibition of apoptosis of tumor cells and 15
16
administering to the patient cyclopamine or a pharmaceutically 17
acceptable salt thereof in a dose that is sufficient to induce apoptosis of said 18
tumor cells and to cause decrease of size or disappearance of the tumor. 19
20
Tas claim 3 recites: 21
3. The method according to claim 2, characterized in that a dose 22
sufficing to induce apoptosis of the tumor cells causes a smaller proportion 23
of normal tissue cells or no normal tissue cells to undergo apoptosis. 24
25
Tas claim 5 recites: 26
5. The method according to claim 4, characterized in that a dose 27
sufficing to induce differentiation and apoptosis of the tumor cells causes a 28
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59

smaller proportion of normal tissue cells or no normal tissue cells to undergo 1
differentiation and apoptosis. 2
3
Tas claim 23 recites: 4
5
23. A method for causing decrease of size or disappearance of a tumor in 6
a human, comprising 7
8
determining that Hedgehog/Smoothened signaling is utilized for 114 9
inhibition of apoptosis of the tumor cells and 10
11
administering to him or to her a medicament comprising cyclopamine 12
or a pharmaceutically acceptable salt thereof or another selective inhibitor of 13
Hedgehog/Smoothened signaling to induce apoptosis of the tumor cells to 14
cause decrease of size or disappearance of the tumor. 15
16
Tas claims reproduced from a clean copy of claims submitted by Tas. Paper 16. 17
See also Ex. 2001. 18
We have considered Tas Motion 14 (Paper 199), Beachy Opposition 14 19
(Paper 324) and Tas Reply 14 (Paper 332). 20
For essentially the reasons articulated in Beachy Opposition 14, as herein 21
discussed, we agree with Beachy and disagree with Tas. 22
Accordingly, Tas Motion 14 will be denied. 23
As noted by Beachy (Paper 324, page 7), Bd.R. 207(b)(2) states: “A claim 24
corresponds to a count if the subject matter of the count, treated as prior art to the claim, 25
would have anticipated or rendered obvious the subject matter of the claim.” 26
27
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60

Therefore, to succeed Tas must demonstrate by a preponderance of the evidence, 1
that the subject matter of Counts 2 and 3, if treated as prior art, would not have 2
anticipated or rendered obvious the subject matter of claims 1, 3, 5, and 23. 3
The rationale in support of Bd.R. 207(b)(2) is explained in University of Southern 4
California v. Depuy Spine, Inc., Interference 105,653, Paper 133, pages 9-10 (BPAI 5
Nov. 23, 2010) (relevant material quoted on pages 7-8 of Beachy Opposition 14 6
(Paper 332)). 7
The basic failure of proof on the part of Tas is a failure to deal with the subject 8
matter of the counts. 9
Rather, except for a few unsupported and conclusory assertions that the claims do 10
not correspond to the count, Tas presents its interpretation of the Beachy application 11
disclosures—that in large measure are not relevant to a proper analysis. Paper 324, 12
page 8:21-22; page 9:17 to page 10:6; page 12:7-9. 13
We agree with Beachy’s observations related to Tas Claims 3 and 5. Paper 323, 14
page 11:8-19. 15
We also agree with the remaining arguments presented in Beachy Opposition 14 16
(Paper 324) responding to arguments made in Tas Motion 14 (Paper 199). 17
For the reasons given, we hold that Tas has failed to meet the burden imposed by 18
Bd.R. 207(b)(2) and therefore Tas Motion 14 is denied. 19
20
VII. Tas Motion 17 21
Tas moves to deny Beachy’s involved application 13/364,121 an earlier 22
constructive reduction to practice (i.e., benefit for the purpose of priority) of: 23
(1) Beachy application 09/685,244 (Ex. 1013) and 24
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61

(2) Beachy application 09/708,964 (now US Patent 7,291,626 B1) 1
(Ex. 1009) as to Count 2. 2
Paper 200, page 1:1-2. 3
The arguments presented and evidence relied upon by Tas in support of Tas 4
Motion 17 are essentially the same as those made in connection with Tas Motion 4 5
(seeking denial of benefit) and Tas Motion 6 (seeking judgment based on lack of written 6
description and indefiniteness). 7
With respect to Tas Motion 17, Tas seeks relief based on alleged lack of a written 8
description for the following limitations
22
: 9
10
Tas Motion 17, Limitation (1) 11
A method for treatment of a human subject having a basal cell carcinoma 12
tumor cell [sic. A basal cell carcinoma tumor]” (or) “A method of therapy 13
for a human subject having a basal cell carcinoma tumor” 14
15
Tas Motion 17, Limitation (2) 16
17
“Comprising administering to the human subject a medicament comprising 18
cyclopamine” (or) “comprising administering to the human subject a 19
therapeutically effective amount of a medicament comprising cyclopamine 20
or a pharmaceutically acceptable carrier” 21
22
Tas Motion 17, Limitation (3) 23
“Wherein Hedgehog/Smoothened signaling is utilized for inhibition of 24
apoptosis of the tumor cell” (or) “wherein said tumor smoothened-dependent 25
hedgehog signaling is utilized for inhibition of apoptosis” 26
27

22
See Paper No. 200 (page numbers not supplied in document)
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62

Tas Motion 17, Limitation (4) 1
2
“And said amount of cyclopamine selectively inhibits smoothened-3
dependent hedgehog signaling in said tumor and is sufficient to induce 4
apoptosis in said tumor and inhibits tumor cell proliferation” (and) “Wherein 5
said medicament is administered in a dose that is sufficient to induce 6
apoptosis of said tumor cell” 7
8
Tas Motion 17, Limitation (5) 9
10
“Causes decrease in size or disappearance of the tumor” 11
12
“Carnival barking,” “Gambling on both sides,” and “plagiarism” See Paper 200, 13
pages 16-18. Our reasoning with respect to each of the limitations and the additional 14
arguments made by Tas is set out in our discussion concerning Tas Motion 4 and Tas 15
Motion 6 and need not be repeated here. 16
For the reasons given in connection with denial of Tas Motion 4 and Tas Motion, 17
we also deny Tas Motion 1. 18
Tas has failed to sustain its burden with respect to Tas Motion 17. 19
Tas Motion 17 will be denied. 20
21
VIII. Beachy Motion 1 22
A. Introduction 23
Beachy moves for judgment against all of Tas’ involved claims 1-23 as lacking 24
written description and/or enablement and/or as being indefinite. Paper 181, page 1:3-5: 25
(1) Tas Claims 2-20 and 23: Beachy argues that there is a lack of a 26
written description and a lack of enablement as to “another compound” or “another 27
inhibitor”. Id. at page 1:6-7. 28
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63

(2) Tas Claim 7: Beachy argues that there is lack of a written description 1
and lack of enablement as to “derivative of cyclopamine”. Id. at, page 1:8. 2
(3) Tas claims 1-23: Beach argues that the term “apoptosis” renders the 3
claims indefinite. Id. at page 1:9-10. 4
The following claims are believed to be representative of the Tas claims at issue 5
(italics added). 6
Independent Tas Claim 1 recites: 7
A method for inducing apoptosis of tumor cells in a tumor-8
bearing 1 patient, comprising 9
10
determining that Hedgehog/Smoothened signaling is utilized 11
for inhibition of apoptosis of tumor cells and 12
13
administering to the patient cyclopamine or a pharmaceutically 14
acceptable salt thereof in a dose that is sufficient to induce apoptosis 15
of said tumor cells and to cause decrease of size or disappearance of 16
the tumor. 17
18
Independent Tas Claim 2 recites: 19
A method for treatment of a patient having a tumor wherein 20
21
Hedgehog/Smoothened signaling is utilized for inhibition of 22
apoptosis of the tumor cells, comprising 23
24
administering to the patient a medicament comprising 25
cyclopamine or another compound that selectively inhibits 26
Hedgehog/Smoothened signaling, wherein said medicament is 27
administered in a dose that is sufficient to induce apoptosis of said 28
tumor cells and causes decrease of size or disappearance of the tumor. 29
30
Dependent Tas Claim 7 recites: 31
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64

The method according to any one of claims 2 to 5, wherein said 1
another compound that selectively inhibits Hedgehog/Smoothened 2
signaling is a derivative of cyclopamine. 3
4
Independent Tas Claim 23 recites: 5
A method for causing decrease of size of disappearance of a 6
tumor in a human, comprising 7
8
determining that Hedgehog/Smoothened signaling is utility for 9
inhibition of apoptosis of the tumor cells and 10
11
administering to . . . [the human] a medicament comprising 12
cyclopamine or a pharmaceutically acceptable salt thereof or another 13
selective inhibitor of Hedgehog/Smoothened signaling to induce 14
apoptosis of the tumor cells to cause decrease of size or disappearance 15
of the tumor. 16
17
Ex. 2001, col. 12:22-38 and 64-67 and col. 14:36-45 (italics added). 18
19
B. Written Description 20
1. “Another Compound” 21
According to Beachy, Tas introduced the “another compound” claims into the Tas 22
application by an amendment filed more than six years after the October 9, 2003 filing 23
date of Tas application 10/682,584 (now the involved Tas patent Ex. 2001) (the “’584 24
application”). Paper 181, page 21:17-20 (citing Ex. 1071, page 21:17-20). 25
Beachy contends that the “another compound” was not described, either expressly 26
or inherently, in either the application or the original claims of either the Tas US ’584 or 27
the Tas PCT ’027 (Ex. 2004) applications as originally filed. Id. at page 21:20-23 (citing 28
First Decl. of Lawrence I. Kruse (Ex. 1070), ¶¶ 27, 29, 31-33). 29
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65

Beachy further contends that the Tas specification does not provide, as part of its 1
invention, any description by way of chemical name, structure, formula, etc., of an 2
inhibitor other than cyclopamine. Id. at page 21:24 to page 22:2 (citing Ex. 1070, 3
¶¶ 19-21 and Exs. 2001, 2002, 2004, 1064, 1067-1068). 4
Beachy still further contends that the Tas disclosure relating to a “derivative of 5
cyclopamine” does not provide written support for the recitation of “another compound” 6
in Tas claims 2-20 and 23. Paper 181, page 22:4-5. 7
Beachy witness Dr. Lawrence Kruse testified that one of ordinary skill in the art 8
would have understood “another compound” to refer to something significantly, and 9
potentially infinitely, broader than the disclosed “derivative of cyclopamine.” Ex. 1070 10
¶ 27:2-4. 11
Beachy argues that, logically, an undefined genus of compounds (such as 12
“derivative of cyclopamine”) cannot provide a written description for an even broader 13
(and potentially infinite) genus of compounds (such as “another compound”). Paper 181, 14
page 22:14-17. 15
Beachy argues further that, even if a person skilled in the art could conclude that 16
the concept of using “another compound” is disclosed in the original Tas disclosure, Tas 17
Claims 2-20 and 23 nonetheless fail to satisfy the written description requirement because 18
the Tas Specification does not disclose any species of “another compound.” Id. at 19
page 23:2-3 and 10-11; Ex. 1070 ¶ 28. 20
Beachy points to the Federal Circuit’s holding in Ariad which states that “… a 21
sufficient description of a genus requires the disclosure of either a representative number 22
of species falling within the scope of the genus or structural features common to the 23
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66

members of the genus so that one of skill in the art can ‘visualize or recognize’ the 1
members of the genus.” Paper 181, page 24 (quoting Ariad, 598 F.3d at 1350). 2
Beachy contends that “zero” cannot constitute “a representative number of 3
species” and, therefore, the Tas specification does not provide adequate written support 4
for the “another compound” recitations in claims 2-20 and 23. Id. at page 23 (citing 5
Ex. 1070, ¶¶ 19-21, 27; Ex. 2001; Ex. 2004; Ex. 1064; Ex. 1067-68). 6
Tas responds that Beachy is taking the claim term “another compound” out of 7
context. Paper 317, page 12:10-11. 8
According to Tas, the claim term “cyclopamine or another compound that 9
selectively inhibits Hedgehog/Smoothened signaling” defines exactly the same set of 10
compounds as the term “a selective inhibitor of Hedgehog/Smoothened signaling.” 11
Id. at page 12:11-14. 12
Tas argues that the Specification has written description and enablement of use of 13
a selective inhibitor of Hh/Smo signaling for treatment of a human having a tumor 14
wherein Hh/Smo signaling is utilized for inhibition of apoptosis of tumor cells. Id. at 15
page 12:14-16. 16
Tas argues further that the set of compounds recited in dependent claim 6 is 17
exactly the same as “a selective inhibitor of Hh/Smo signaling that binds to the biological 18
target of cyclopamine.” Id. at page 12:17 to page 13:1. 19
Dependent claim 6 recites: “[t]he method according to any one of claims 2 to 5, 20
wherein said another compound that selectively inhibits Hedgehog/Smoothened signaling 21
is a compound that binds to the same biological target as cyclopamine to exert said 22
inhibition.” Ex. 2001, col. 12:59-63. 23
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67

Tas argues that the written description and enablement of the subject matter 1
claimed does not require any special description or showing of structure of “another” 2
compound. Paper 317, page 13:5-6. 3
According to Tas, a broad genus of selective inhibitors of Hh/Smo signaling, 4
including those structurally totally unrelated to cyclopamine, were generally known in the 5
art. Id. at page 13:7-8. 6
Tas points to Johan Ericson et al., Two critical periods of Sonic Hedgehog 7
signaling required for the specification of motor neuron identity, 87 CELL, 661-673 8
(1996) (Ex. 2052), which is said to teach generation of “polyclonal (H4) and monoclonal 9
(MAb 5E1) antibodies [directed] against the biologically active amino-terminal fragment 10
of SHH (SHH-N)” and that addition of “H4 IgG blocked the SHH-N-mediated induction 11
of floor plate cells and motor neurons.” Id. at page 3:11-13 (citing Ex. 2052 at page 662). 12
Tas also points to John P. Incardona et al., The teratogenic Veratrum alkaloid 13
cyclopamine inhibits Sonic hedgehog signal transduction, 125 DEVELOPMENT 3553-3562 14
(1998) (Ex. 2054) said to describe employment of anti-Shh polyclonal H4 antibodies to 15
selectively inhibit Hh activity, but which also states that veratramine, which is formed by 16
acid aromatization of cyclopamine, does not cause cyclopia in sheep (presumably by 17
failing to selectively inhibit Hh signaling). Ex. 2054 at page 3556). 18
Tas also offers Exhibits 2107, 2109-2111 and 2035 to demonstrate that other 19
inhibitors of Smo/Hh signaling were known in the art at the time of invention. Paper 317, 20
pages 3-4. 21
Tas further contends that Beachy misapplies the law, arguing that, in Ariad, there 22
was no compound that inhibited NF-KB activity at the time of the application and that 23
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68

there was no prior art describing a compound known to inhibit NF-KB activity. Id. at 1
page 18:5-13 2
In the present case, Tas argues that a genus of compounds having over a dozen 3
structurally diverse species that selectively inhibit Hh/Smo signaling was common 4
general knowledge besides the cyclopamine used for the exemplification of invention. 5
Id. at page 18:11-13. 6
Tas also argues that, contrary to Beachy’s assertions, the limitation “another 7
compound that selectively inhibits Hh/Smo signaling” “is inherent and necessarily 8
implicit in the original application and description of the disclosed treatment of target 9
tumors.” Id. at page 18:14- 18 (citing Lockwood v. American Airlines, Inc., 107 F.3d 10
1565, 1572 (Fed. Cir. 1997). 11
According to Tas, the limitation is necessarily disclosed in the original application. 12
Id. at 18. 13
Beachy replies that Tas’ argument is without merit and, factually, reveals Dr. Tas’ 14
lack of understanding of the involved technology. Paper 334, page 2:3-4. 15
According to Beachy, the relevant legal analysis is not whether those skilled in the 16
art were aware of a genus of structurally diverse selective inhibitors of the Hh/Smo 17
pathway. Id. at page 2:5-7. 18
Rather, Beachy argues that the issue is whether the original Tas application would 19
have conveyed to one skilled in the art that Dr. Tas was aware of a broad genus of 20
selective inhibitors that Dr. Tas believed could be used in his claimed methods. Id. at 21
page 2:7-9. 22
Beachy asserts that there is no statement anywhere in the original Tas application 23
to suggest that Tas believed his claimed methods encompassed a broad genus of Hh 24
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69

pathway inhibitors having unlimited structural diversity and completely undefined modes 1
of achieving inhibition of the pathway. Id. at page 2:10-13. 2
Rather, according to Beachy, Tas described and exemplified a single compound: 3
cyclopamine. Id. at, page 2:13-14. 4
Beachy presents additional arguments in support of its response to Tas Opposition 5
1. Id. at page 2:3 to page 4:17. 6
We are persuaded by Beachy’s arguments. 7
Section 112 requires that the description must “clearly allow persons of ordinary 8
skill in the art to recognize that [the inventor] invented what is claimed.” Vas–Cath Inc. 9
v. Mahurkar, 935 F.2d 1555, 1563 (Fed. Cir. 1991) (citing In re Gosteli, 872 F.2d 1008, 10
1012 (Fed. Cir. 1989)). 11
The test for sufficiency is whether the disclosure of the application relied upon 12
reasonably conveys to those skilled in the art that the inventor had possession of the 13
claimed subject matter as of the filing date. Ariad, 598 F.3d at 1351. 14
Tas points to the contemporary scientific art in an attempt to demonstrate that 15
selective Hh pathway inhibitors were well-known in the art and, based on that art, 16
contends that a person of ordinary skill in the art would thus have known that Tas had 17
possession of the claim term “another compound” as comprised by the selective Hh 18
inhibitors then described and used in the scientific literature. 19
However, the use of “another compound that selectively inhibits 20
Hedgehog/Smoothened signaling” does not define the entire scope of Tas’ invention. 21
On the contrary, the remainder of the limitation of claim 2 recites: “wherein said 22
medicament is administered in a dose that is sufficient to induce apoptosis of said tumor 23
cells and causes decrease of size or disappearance of the tumor.” 24
Interferences 105,926 & 105,949

70

Tas points to no reference that indicates that any of the known selective Hh 1
signaling inhibitors at the time of invention were known to be at all effective in the 2
treatment of tumors so as to cause them to decrease in size or disappear. 3
For example, Exhibit 2107 describes the effect of Hh suppression on zebrafish 4
retinal differentiation. Exhibit 2108 demonstrates that Hh signaling suppression results 5
in partial cyclopia and other specific midline abnormalities in zebrafish, suggesting a 6
genetic model for human holoprosencephaly. 7
Exhibit 2109 and Exhibit 2110 suggest that the 20 kDa NH2-terminal fragment of 8
Hh plays an important role in ptc receptor activation in the hedgehog signaling 9
mechanism. 10
Exhibit 2011 explores the role of Hh on both proliferation and cell-type 11
determination in pituitary gland development. 12
Exhibit 2052 demonstrates the role played by Hh in regulating the generation of 13
floor plate cells and motor neurons. 14
None of these prior art references speak to the subject matter of the invention 15
recited in Tas Claim 2, viz., the treatment of tumors; indeed Beachy persuasively argues 16
that these effects are generally focused at Hh signaling activity at a level upstream of the 17
ptc mutation (which is commonly found in BCC tumor cells) and are therefore not 18
particularly relevant respect to treatment of tumors. See Paper 334, page 4. 19
Taken in toto, we can find little support based on the prior art called to our 20
attention by Tas to establish that a person of ordinary skill would have known that Tas 21
was in possession of (1) “another compound that selectively inhibits 22
Hedgehog/Smoothened signaling” that (2) would be effective in the reduction in size and 23
disappearance of tumors. 24
Interferences 105,926 & 105,949

71

Moreover, Tas’ reliance on In re Smythe, 480 F.2d 1376, 1384 (CCPA 1973) is 1
misplaced. 2
Tas cites Smythe as holding that one need not “include descriptions of the very 3
many structural or functional equivalents of disclosed elements or steps which are already 4
stored in the minds of those skilled in the arts, ready for instant recall upon reading the 5
descriptions of specific elements or steps” as support for its argument that, because 6
selective Hh signaling inhibitors were known in the art, a person of ordinary skill would 7
have known that Tas had possession of “another compound.” Paper 317, page 13:13-19 8
However, as Beachy correctly points out, the case in Smythe was not one in which 9
there was “any unpredictability such that appellants’ description of air or other inert gas 10
would not convey to one skilled in the art knowledge that appellants invented an analysis 11
system with a fluid segmentizing medium.” Smythe, 480 F.2d at 1383. 12
The Smythe court elaborated that: “ 13
[I]n other cases, particularly but not necessarily, chemical cases, 14
where there is unpredictability in performance of certain species or 15
subcombinations other than those specifically enumerated, one 16
skilled in the art may be found not to have been placed in possession 17
of a genus or combination claimed at a later date in the prosecution 18
of a patent application. 19
20
Id. (citing, e.g., In re DiLeone (DiLeone II), 436 F.2d 1033 (CCPA 1971), and In re 21
DiLeone (DiLeone I) 436 F.2d 1404 (CCPA 1971). 22
In the instant case, which deals with a method of using a chemical composition in 23
the treatment of tumors, we find that Tas has not established that there is sufficient 24
certainty that a person of ordinary skill in the art, and knowing the then current state of 25
the art, would have known that Tas had in its possession “another compound that 26
Interferences 105,926 & 105,949

72

selectively inhibits Hedgehog/Smoothened signaling” that would be effective in the 1
reduction in size and disappearance of tumors. 2
Given the uncertainty of the chemical arts, and the nature of the proofs adduced by 3
Tas, we conclude that Tas claims 2-6, 8-20 and 23 are unpatentable under 35 U.S.C. 4
§ 112 for lack of written description. 5
Because we find the claims unpatentable for lack of written description, we do not 6
reach Beachy’s arguments that the claims are also unpatentable under 35 U.S.C. § 112 for 7
lack of enablement with respect to this limitation. 8
9
2. “Derivative of cyclopamine” 10
The Tas Specification explicitly provides the following definition of the claim term 11
“derivative of cyclopamine”: 12
It is specifically contemplated that molecules can be derived from 13
cyclopamine or synthesized in such a way that they possess structural 14
features to exert similar receptor binding properties and 15
biological/therapeutic effects as cyclopamine. Such a molecule is 16
called here a “derivative of cyclopamine” and defined as follows: A 17
molecule that contains the group of atoms of the cyclopamine 18
molecule required for the binding of cyclopamine to its biological 19
target but contains also modifications of the parent cyclopamine 20
molecule in such ways that the newly derived molecule continues to 21
be able to bind specifically to the same biological target to exert the 22
biological effects of cyclopamine disclosed herein. Such 23
modifications of cyclopamine may include one or more permissible 24
replacement of or a deletion of a molecular group in the cyclopamine 25
molecule or addition of a molecular group (particularly a small 26
molecular group such as the methyl group) to the cyclopamine 27
molecule, provided that the resultant molecule is stable and possesses 28
the capability of specific binding to the same biological target as 29
cyclopamine to exert the biological effects described herein. 30
Interferences 105,926 & 105,949

73

Derivation of such new molecules from cyclopamine can be readily 1
achieved by those skilled in the art and the possession or lack of the 2
biological effects of cyclopamine in the newly derived molecule can 3
also be readily determined by those skilled in the art by testing for the 4
biological effects disclosed herein. 5
6
Ex. 2001, col. 6, ll. 1-26. 7
Beachy argues that Tas Claim 7 lacks adequate written description under 35 U.S.C. 8
§112, first paragraph with respect to the claim term “derivative of cyclopamine”. 9
Paper 181, page 23:15 to page 24:4. 10
According to Beachy, the Tas disclosure fails to provide “either a representative 11
number of species falling within the scope of the genus or structural features common to 12
the members of the genus so that one of skill in the art can ‘visualize or recognize’ the 13
members of the genus.” Id. (quoting Ariad, 598 F.3d at 1350). 14
Furthermore, argues Beachy, Tas’ definition of a “derivative of cyclopamine” fails 15
to identify a single representative species of a derivative of cyclopamine by name, 16
formula, or structure. Id. at page 24:8-9. 17
Beachy argues that one of ordinary skill in the art would have understood that, in 18
addition to not identifying any specific “derivative of cyclopamine,” the Tas application 19
does not identify which, if any, “permissible” additions, deletions, or replacements of 20
molecular groups on the cyclopamine molecule would result in a derivative molecule 21
having the functional properties identified in the definition of “derivative of 22
cyclopamine” (e.g., “structural features to exert similar receptor binding properties and 23
biological/therapeutic effects as cyclopamine”; “containing the group of atoms of the 24
cyclopamine molecule required for the binding of cyclopamine”; or “continues to be able 25
Interferences 105,926 & 105,949

74

to bind specifically to the same biological target to exert the biological effects of 1
cyclopamine disclosed herein”). Id. at page 13:19-14:11. 2
Tas responds by arguing that the prior art evidence taught that cyclopamine and a 3
single derivative species of cyclopamine inhibits Hh/Smo signaling at the level of Smo. 4
Paper 317, page 21:7-8 (citing Ex. 2035
23
). 5
Tas also responds by arguing that Beachy does not explain why the Beachy 6
specification, if taken as prior art, discloses numerous derivatives of cyclopamine. Id. at 7
page 21:9-12(citing Ex. 1018 at cols. 19:41 to 32:16 and 69:25 to 133:54). 8
We are persuaded by Beachy’s arguments. 9
The Tas Specification provides not a single example of a cyclopamine derivative. 10
The definition of cyclopamine derivatives that appears in the Tas Specification, 11
apart from single statement suggesting that small molecular groups, such as methyl might 12
be suitable, is indeterminate with respect to the nature of the substitutions or 13
rearrangements that might be made. 14
It is also indefinite as to specific substitutions or locations on the cyclopamine that 15
might be made “in such a way that they possess structural features to exert similar 16
receptor binding properties and biological/therapeutic effects as cyclopamine.” Ex. 2001, 17
col. 6:1-4. 18
The Tas Specification also fails to specify any of the structural features common to 19
the members of the genus. 20

23
Talpale et al., Effects of oncogenic mutations in Smoothened and Patched can be
reversed by cyclopamine, 406 NATURE1005 (2000).

Interferences 105,926 & 105,949

75

Rather, the Tas Specification provides only generalized descriptions of what might 1
possibly constitute a derivative of cyclopamine. 2
The level of detail required to satisfy the written description requirement of § 112 3
varies depending on the nature and scope of the claims and on the complexity and 4
predictability of the relevant technology. Capon v. Eshhar, 418 F.3d 1349, 1357-58 5
(Fed. Cir. 2005). 6
With respect to generic claims in the chemical arts, the Federal Circuit has held 7
that a sufficient description of a genus generally requires the disclosure of either a 8
representative number of species falling within the scope of the genus or structural 9
features common to the members of the genus so that one of skill in the art can “visualize 10
or recognize” the members of the genus. Ariad, 598 F.3d at 1350 (citing Eli Lilly, 119 11
F.3d at 1568-69). 12
The Tas Specification satisfies neither of these requirements; it provides no 13
disclosure of any species of cyclopamine derivative, nor does it identify with any 14
specificity any structural features common to the members of the genus. 15
Furthermore, Tas’ argument that a person of ordinary skill would appreciate from 16
the prior art that Tas possessed cyclopamine derivatives is not persuasive. 17
Tas offers but a single example of a single derivative of cyclopamine in the prior 18
art that had an inhibitory effect on Hh/Smo signaling: 3-keto, N-aminoethyl 19
aminocaproyl dihydrocinnamoyl cyclopamine (KAAD-cyclopamine). Ex. 2035, 20
page 1007:1-2. 21
We find that a single disclosure of a single effective derivative is not sufficient in 22
this case to establish that a person of skill in the art would appreciate that Tas had 23
possession of the genus. 24
Interferences 105,926 & 105,949

76

Moreover, with respect to Tas’ argument that Beachy fails to explain why the 1
Beachy [Specification], “taken as prior art” is not an admission that cyclopamine 2
derivatives were indeed well-known in the prior art, Tas adduces no proof that the 3
information in the Beachy Specification (Ex. 1018) was known to those skilled in the art 4
prior to the Tas filing date.
24
5
Section 112 requires that one of skill in the art can “visualize or recognize” the 6
claimed genus based on the Specification’s disclosure, i.e., it must demonstrate 7
constructive possession. Eli Lilly, 119 F.3d at 1568; Ariad, 598 F.3d at 1352. 8
We find that the Tas Specification fails to do so because it fails to provide any 9
examples of species of cyclopamine derivatives and further fails to adequately describe 10
structural features common to the members of the genus. 11
Furthermore, the state of the prior art was not so developed that a person of skill in 12
the art would believe that Tas was in possession of the genus and species. 13
We therefore conclude that claim 7 is unpatentable under 35 U.S.C. §112 for lack 14
of written description. 15
We do not reach Beachy’s argument with respect to lack of enablement of this 16
claim limitation. 17
18
C. Indefiniteness 19
Beachy argues that Tas claims 1-23 are indefinite under 35 U.S.C. § 112, second 20
paragraph, with regards to the term “apoptosis.” Paper 181, page 30:7-8. 21

24
The Beachy ’076 application was filed on October 13, 2000, but was not published,
and issued as US Patent 7,098,196 B1 on August 29, 2006. The Tas ’584 application was
filed on October 9, 2003 and issued as US 7,893,078 B2 on Feb. 22, 2011.
Interferences 105,926 & 105,949

77

According to Beachy, each of the Tas claims require the induction of “apoptosis” 1
in tumor cells, among other biological effects, following the administration of a 2
medicament. Id. at page 31:4-5. 3
Beachy contends that there is no dispute that one of ordinary skill in the art in the 4
years 2001-2003 would have understood the term “apoptosis” to refer to a particular type 5
of cell death that is characterized by particular morphological and biochemical hallmarks. 6
Id. at page 31:11-14 (citing Ex. 2006, Abstract, pp. 244-251, Fig. 5; Ex. 1043, p. 55; 7
Ex. 2008, pp. 528-30; Ex. 1048, p. S99; Ex. 1046, p. 218; Ex. 1045, ¶15). 8
Beachy argues that, in the 2001-2003 timeframe, one of ordinary skill in the art 9
would have known that specific techniques and assays were used to evaluate whether 10
cells have undergone apoptosis. Id. at page 31:16-18. 11
Specifically, Beachy argues that during 2001-2003, those of ordinary skill 12
in the art relied upon highly precise and highly quantitative morphological techniques 13
evaluate several specific morphological characteristics of an apoptotic cell. Id. at page 14
31:19 to page 32:1 (citing Ex. 2006, pages 244-251, Fig. 5; Ex. 1043, page 55; Ex. 2008, 15
pages 528-30; Ex. 1048, page S99; Ex. 1046, page 218; Ex. 1045, ¶15-16). 16
Beachy points out that those of ordinary skill in the art employed particular 17
biochemical assays such as DNA-laddering and TUNEL assays. Id. at page 32:3-5 18
(citing Ex. 2008, Abstract; Ex. 1045, ¶¶ 22-25). 19
According to Beachy witness Dr. Andreas Strasser, one of ordinary skill in the art 20
understood that it was necessary to employ these techniques to evaluate the unique 21
morphological and biochemical hallmarks of an apoptotic cell. Id. at page 32:5-8 (citing 22
Ex. 2008, Abstract; Ex. 1045, ¶¶19, 20, 22-25). 23
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78

Dr. Strasser testified that one skilled in the art would have understood that the use 1
of these techniques was important in assuring that the term “apoptosis” was properly 2
being used to describe a particular type of programmed cell death. Id. at page 32:8-12 3
(citing Ex. 1045, ¶¶ 19, 22-25). 4
Beachy argues that the experiments disclosed in the Tas Specification did not 5
describe art-recognized techniques in stating a conclusion that the topical administration 6
of cyclopamine induced “apoptosis” of tumor cells. Id. at page 32:13-15 (citing 7
Ex. 2001; Ex. 2002; Ex. 2004; Ex. 1045, ¶¶ 26, 28, 29, 30, 31, 32). 8
According to Beachy, one of ordinary skill in the art would have considered the 9
morphological images to be of poor quality and insufficient to identify apoptotic cells. 10
Id. at page 32:16-18(citing Ex. 1045, ¶ 31). 11
Beachy further contends that one of ordinary skill in the art would have recognized 12
that Tas did not employ any biochemical techniques to assess apoptotic activity. Id. at 13
page 32:18-20 (citing Ex. 2001; Ex. 1045, ¶¶26, 30). 14
Therefore, Beachy argues that one of ordinary skill in the art would have 15
recognized that Tas did not employ the art-recognized techniques for characterizing 16
apoptotic activity and, consequently, that Tas’ use of the term “apoptosis” was not 17
substantiated. Id. at page 33:1-3 (citing Ex. 2001; Ex. 2002; Ex. 2004; Ex. 1045, ¶¶ 26, 18
28, 29, 30, 31, 32). 19
Beachy contends that one of ordinary skill in the art would have considered Tas’ 20
use of the term “apoptosis” as diverging from the ordinary or common meaning of the 21
term, and that Tas did so without reasonable clarity, deliberateness, or precision. Id. at 22
page 33:4-8 (citing Ex. 1045, ¶¶53-54). 23
Interferences 105,926 & 105,949

79

Beachy argues further that one of ordinary skill in the art would have further 1
questioned Tas’ use of the term “apoptosis” because Tas relies upon the observation of 2
“cystic spaces” within the treated tumors. Id. at page 33:9-12. 3
One of ordinary skill in the art is said to have not recognized “cystic spaces,” 4
which Beachy contends may occur for reasons wholly unrelated to apoptosis. Id. at 5
page 33:11-12 6
Therefore, Beachy argues that one of ordinary skill in the art would have 7
considered the reference to cystic spaces as evidence of apoptotic activity to further 8
suggest that Tas was using the term “apoptosis” in an unconventional manner. Id.at 9
page 33:16-19 (citing Ex. 1060, pages 262, 264, 265, Figs. 3-4; Ex. 1061, page 826; 10
Ex. 1062, page 3; Ex. 1045, ¶¶33-34). 11
According to Beachy, one of ordinary skill in the art, knowing that there can be 12
significant levels of apoptotic activity in BCC tumors prior to any treatment, would have 13
recognized that Tas’ experiments described in the Specification did not have proper 14
controls to exclude the possibility that any observed apoptosis was not induced by the 15
administration of cyclopamine. Id. at page 34:3-5 (citing Ex. 2006, page 253; Ex. 1045, 16
¶ 50). 17
Therefore, Beachy argues, one of ordinary skill in the art would not have known 18
how Tas could have distinguished naturally occurring apoptosis from induced apoptosis, 19
thereby making it impossible to discern the metes and bounds of Tas’s claims. Id. at page 20
34:6-8 (citing Ex. 2006, page 253; Ex. 1045, ¶ 50). 21
Beachy summarizes by arguing that, by applying the ordinary meaning of the term 22
“apoptosis” and the art-accepted criteria for assessing apoptosis, one skilled in the art 23
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80

would not consider the data presented in the Tas Specification as satisfying the Tas 1
claims. Id. at page 34:10-14 (citing Ex. 1045, ¶¶ 53-54). 2
On the other hand, argues Beachy, applying a non-conventional interpretation of 3
the term “apoptosis” to refer to undefined and imprecise morphological characteristics, 4
no biochemical hallmarks, and the presence of “cystic spaces,” one skilled in the art 5
would very likely reach an opposite conclusion. Id. at page 34:15-18 (citing Ex. 1045, 6
¶¶ 53-54). 7
Beachy argues that this ambiguity presents an insoluble dilemma for one of 8
ordinary skill in the art attempting to interpret the scope of Tas claims 1-23, thereby 9
rendering the claims indefinite under § 112. Id. at page 34:19 to page 35:1. 10
In response, Tas argues that apoptosis was a term widely used and well 11
understood in prior art and its morphological features were common knowledge. 12
Paper 317, page 22:2-3. 13
According to Tas, identification of cells undergoing apoptosis on the basis of 14
morphological criteria was routinely practiced in the art. Id. at page 22:3-4 (citing 15
Ex. 2098, ¶ 47-49; Exs. 2008, 2019, Ex. 2047, Exs. 2123-2128). 16
Tas argues that examination of hematoxylin- and eosin- stained tissue sections 17
under high magnification (x1000) was particularly recognized to provide a reproducible, 18
quantitative means to identify cells undergoing apoptosis. Id. at page 22:5-7 (citing 19
Ex. 2127; Ex. 2001; Ex. 2004). 20
Tas argues Dr. Strasser admits that the use of morphological criteria for 21
identification of the cells undergoing apoptosis was well known in prior art. Id. at 22
page 22:10-12 (citing Ex. 1045, ¶ 16-19). 23
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81

Tas argues that the use of morphological criteria for identification and counting of 1
apoptotic cells in stained tissue sections was a preferred and widely-practiced method in 2
the art at the time of invention, due to its reproducibility, practicality, suitability to 3
clinical practice. Id. at page 23:8-12 (citing Ex. 2047, Exs. 2123-2125, Ex. 2127). 4
Tas argues further that Beachy provides no evidence that the examples presented in 5
the Tas Specification cannot be replicated or that use of “state of the art” biochemical 6
markers suggested by Beachy would lead to a different conclusion. Id. at page 22:13-15. 7
According to Tas, Beachy’s contention that a skilled person would not recognize 8
what was meant by the claim term “apoptosis” unless it was determined by an alleged 9
“state of the art” method is baseless. Id. at page 22:15-17. 10
Tas also disputes Beachy’s argument that that “Tas did not use art-recognized 11
techniques” for detection of apoptotic cells, lacked controls to determine the frequency of 12
naturally-occurring apoptosis in tumor cells, and that “Tas’ reference to cystic spaces as 13
evidence of apoptotic activity” further suggests a divergent use of the apoptosis term, are 14
misrepresentations. Id. at page 24:8-12 15
Tas cites prior Exhibits 2008, 2009, 2123-2125, 2127, 2128 as indicative of what 16
constituted “art-recognized” techniques. Id. at page 24:12-13. 17
Tas also points to its Specification as disclosing both controls and that the 18
appearance of cystic spaces are a consequence of massively and rapidly induced 19
apoptotic elimination of tumor cells (and not as evidence of apoptotic activity). Id. at 20
page 24:12-13 (citing Ex. 2004, page 4:13-15). 21
Beachy replies that neither the words nor the photographs contained in the Tas 22
disclosure discuss or reflect any art-recognized morphological features that are unique to 23
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82

apoptotic cells (which Tas exhibits describe as blebs, spikes and blisters. Paper 334, 1
page 12:7-10 (citing, e.g., Ex. 2047, page 1102)). 2
Importantly, argues Beachy, several Tas exhibits emphasize the technical 3
difficulties associated with assessing apoptotic activity in tissue sections, the 4
considerable variation of apoptosis within untreated tumors, and the potential bias 5
and lack of reproducibility in experiments using a small number of samples, such as 6
those in the Tas specification. Id. at page 12:10-14 (citing Ex. 1114, ¶¶ 37-45; Ex. 2009, 7
page 14; 1st col). 8
“Whether a claim is invalid for indefiniteness requires a determination whether 9
those skilled in the art would understand what is claimed when the claim is read in light 10
of the specification.” Morton Int’l, Inc. v. Cardinal Chem. Co., 5 F.3d 1464, 1470 (Fed. 11
Cir. 1993). 12
Claims can be indefinite when: (1) a claim recites means-plus-function elements 13
without disclosing corresponding structure in the specification; includes a numeric 14
limitation; (2) the claims fail to disclose which of multiple methods of measuring that 15
number should be used; (3) a claim term is “completely dependent on a person's 16
subjective opinion”; and (4) a claim term does not have proper antecedent basis where 17
such basis is not otherwise present by implication or the meaning is not reasonably 18
ascertainable. Halliburton Energy Services, Inc. v. M-I LLC, 514 F.3d 1244, 1249 (Fed. 19
Cir. 2008). 20
The common thread in indefiniteness cases is that claims were held indefinite only 21
where a person of ordinary skill in the art could not determine the bounds of the claims, 22
i.e., the claims are insolubly ambiguous. Id. 23
We are not persuaded by Beachy’s arguments. 24
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83

It is true that the Tas Specification does not provide an explicit definition of 1
“apoptosis”. 2
But there is no dispute that the term had a well-defined meaning in the art at the 3
time of Tas’ invention. 4
Beachy witness Dr. Strasser testified that, in 2001, the terms “apoptosis” and 5
“programmed cell death” were largely considered synonymous and were defined as a 6
form of cell death in which the cell receives physiological (e.g., growth factor 7
withdrawal) or pathological (e.g., treatment with DNA damage inducing 8
chemotherapeutic drugs) signals that trigger a programmed sequence of events leading to 9
the ultimate elimination of the cell. (Ex. 1045, ¶ 15). 10
Dr. Strasser further testified that: 11
Apoptosis can be characterized by a series of morphological changes 12
in cells. These changes include: (a) shrinkage of the cell and nucleus, 13
(b) condensation of chromatin (pyknosis), (c) nuclear fragmentation 14
(karyorrhexis) [nucleus breaks into discrete chromatin bodies or 15
nucleosomal fragments due to DNA degradation], (d) membrane 16
budding ultimately leading to formation of membrane-bound vesicles, 17
i.e., so-called apoptotic bodies, and (e) elimination of apoptotic cells 18
and bodies by phagocytosis. 19
20
Ex. 1045, ¶ 16 (citing Ex. 2006, pages 244-251, Fig. 5; Ex. 1043, page 55; Ex. 2008, 21
pages 528-30; Ex. 1048, page S99; Ex. 1046, page 218). 22
Dr. Strasser still further testified that: 23
The Tas Paper on Apoptosis (Paper No. 92) refers to morphological 24
features and criteria associated with apoptosis, but this paper does not 25
state what morphological features/criteria are used to identify 26
apoptosis in Tas’ PCT ’027 (Ex. 2002), US ’584 (Ex. 2004), and USP 27
’078 (Ex. 2001). Similarly, Tas’ PCT ’027, US ’584, and USP ’078 28
also refer to morphological features and criteria associated with 29
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84

apoptosis, but do not state what morphological features/criteria are 1
used to identify apoptosis in those documents. 2
3
Ex. 1045, ¶ 28. 4
Dr. Strasser, after giving examples, concluded that the illustrations in the Tas 5
Specifications “fail to meet the art-recognized minimum requirements for determining 6
that apoptosis is present or is evident, especially with regards to determining a 7
quantitative amount of apoptosis” and that “Tas does not present the results from any 8
assay techniques based on biochemical markers, such as employing the TUNEL assay, 9
which was conventionally used in apoptosis studies, including throughout 2001-2004.” 10
Ex. 1045, ¶ 30. 11
However, the indefiniteness analysis under 35 U.S.C. § 112 does not address 12
whether the quality of the analysis produced in the examples of the Specification meets 13
“art-recognized standards,” but rather whether the claim term “apoptosis,” when viewed 14
in light of the Tas Specification, would be insolubly ambiguous to a person of ordinary 15
skill in the contemporary art. Halliburton, 514 F.3d at 1249. 16
We find that Beachy has not met its burden in this respect. 17
Beachy admits that the term apoptosis was well-known at the time of invention, 18
but adduces insufficient evidence to demonstrate that a person of ordinary skill in the art 19
at the time of Tas’ invention would have found Tas’ employment of the term “apoptosis” 20
in the claims to have been insolubly ambiguous. 21
Furthermore, Dr. Strasser seems to admit that the Tas Paper refers to 22
morphological features and criteria associated with apoptosis, but does not state that the 23
criteria discussed in the Tas Paper are ambiguous or confusing when compared with the 24
prior art. 25
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85

Beachy voices a number of criticisms of the experimental methodology and the 1
quality of the figures disclosed in the Tas Specification, but these concerns do not amount 2
to a showing of indefiniteness. 3
More to the point, Beachy does not convincingly demonstrate that the disclosures 4
of the Tas Specification contradict or differ from the teachings of the prior art in such a 5
way that would present an insoluble ambiguity to the artisan of ordinary skill. 6
Consequently, Beachy has not met its burden of showing that a person of ordinary 7
skill in the art would have been irretrievably confused by what Tas meant when using the 8
term “apoptosis.” 9
Beachy’s Motion 1 seeking judgment against Tas Caims 1-23 on the ground of 10
indefiniteness will be denied. 11
12
D. Decision on Beachy Motion 1 13
Beachy Motion 1 for judgment against claims 2-20 and 23 as being unpatentable 14
under 35 U.S.C. § 112 for lack of written description will be granted. 15
Beachy Motion 1 for against claims 1-23 as being unpatentable under 35 U.S.C. 16
§ 112 as indefinite will be denied. 17
18
IX. Beachy’s Contingent Motions and Responsive Motion 3 19
A. Beachy Motion 2 20
Beachy Motion 2 is contingent on the Board granting Tas Motions 4 and/or 17 (to 21
deny Beachy priority benefit). Paper 311, page 1 at 1. 22
Because we have denied Tas Motions 4 and 17, we need not reach Beachy 23
Contingent Motion 2. 24
Interferences 105,926 & 105,949

86

Beachy Motion 2 will be dismissed as moot. 1
2
B. Beachy Motion 3 3
Beachy Responsive Motion 3 is contingent upon the Board granting Tas Motion 6 4
and entering judgment against all of Beachy’s claims involved in the interference. 5
Paper 312, page 1. 6
Because we have denied Tas Motion 6, we need not reach Beachy Responsive 7
Motion 3. 8
Beachy’s Motion 3 will be dismissed as moot. 9
10
X. Motions to strike 11
Both parties have filed motions to strike. Paper 345 (Tas Motion 18) and 12
Paper 342 (Beachy Motion 4). 13
We have elected to consider all arguments on the merits and therefore deny both 14
motions to strike. 15
Both motions will be denied. 16
17
XI. Order 18
Upon consideration of the motions filed, and for the reasons given, it is 19
ORDERED that Tas Motion 2 is denied. 20
FURTHER ORDERED that Tas Motion 3 is granted. 21
FURTHER ORDERED that Tas Motion 4 is denied. 22
FURTHER ORDERED that Tas Motion 6 is denied. 23
FURTHER ORDERED that Tas Motion 14 is denied. 24
Interferences 105,926 & 105,949

87

FURTHER ORDERED that Tas Motion 17 is denied. 1
FURTHER ORDERED that Tas Motion 18 is denied. 2
FURTHER ORDERED that Beachy Motion 1 is granted as to lack of written 3
description and denied as to indefiniteness. 4
FURTHER ORDERED that Beachy Motion 2 is dismissed. 5
FURTHER ORDERED that Beachy Motion 3 is dismissed. 6
FURTHER ORDERED that Beach Motion 4 is denied. 7
8
XII. Disposition of interferences 9
The earliest date accorded to Tas is subsequent to the earliest date accorded to 10
Beachy. 11
In its priority statement, Tas does not allege a date of invention prior to the date 12
accorded to Beachy. 13
Accordingly, on the issue of priority, junior party Tas has not established that it 14
can prevail on priority. 15
A judgment against Tas on the issue of priority is entered in a separate paper. 16
17
Interferences 105,926 & 105,949

88

cc (via email): 1
2
Attorney for Tas: 3
4
Walter J. Steinkraus 5
Email: wsteinkraus.@live.com 6
7
Dr. Sinan Tas, pro se 8
Email: sinan.tas1@gmail.com 9
10
Attorney for Beachy: 11
12
Anthony J. Zelano 13
Brion P. Heaney 14
John A. Sopp 15
Millen, White, Zelano & Branigan, PC 16
Email: zelano@mwzb.com 17
Email: Heaney@mwzb.com 18
Email: sopp@mwzb.com 19
20
Oliver R. Ashe, Jr. 21
Ashe, PC 22
Email: oashe@ashepc.com 23
24