Ex Parte Reich et al

Patent Trial and Appeal Board

Feb 24, 2016

11615554 (P.T.A.B. Feb. 24, 2016)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
11/615,554 12/22/2006 Samuel Jotham Reich 140613.01001 1077
21269 7590 02/25/2016
PEPPER HAMILTON LLP
500 GRANT STREET
SUITE 5000
PITTSBURGH, PA 15219-2507
EXAMINER
SCHNIZER, RICHARD A
ART UNIT PAPER NUMBER
1674
MAIL DATE DELIVERY MODE
02/25/2016 PAPER
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte SAMUEL JOTHAM REICH and NADINE DEJNEKA1
____________

Appeal 2013-004817
Application 11/615,554
Technology Center 1600
____________

Before JEFFREY N. FREDMAN, ULRIKE W. JENKS, and
RICHARD J. SMITH, Administrative Patent Judges.

SMITH, Administrative Patent Judge.

DECISION ON APPEAL

This is an appeal under 35 U.S.C. § 134 involving claims to a method
for inhibiting expression of a human complement system or a complement
system regulator mRNA. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.

1 According to Appellants, the real party in interest is OPKO
PHARMACEUTICALS, LLC. (Appeal Br. 2.)
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STATEMENT OF THE CASE
Background
The complement system includes some 30 proteins that circulate
in the extracellular fluid capable of launching a non-antigen
specific immune response against invading bacterial and viral
pathogens. Complement system proteins are circulated in an
inactive form and become activated when a molecular pattern on
the surface of an invading microorganism is recognized by early
components of the system.

(Spec. ¶ 2.)
Claims on Appeal
Claims 24–31, 34, 35, 37, 40, 41, 43, 45–48, 50, 53, and 54 are on
appeal. (Appeal Br. 18–21.) Independent claim 24 is illustrative and reads
as follows:
24. A method for inhibiting expression of a human complement system or
a complement system regulator mRNA comprising:

administering to a subject in need thereof an effective amount of an
siRNA having a sense RNA strand including a nucleotide sequence
substantially identical to a target sequence of about 19 to about 25
contiguous nucleotides in human C3 protein mRNA, wherein said
target sequence comprises a nucleotide sequence substantially identical to,
SEQ ID NO: 45, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 51, or SEQ
ID NO: 56 and an antisense RNA strand substantially complementary to the
sense RNA strand, wherein the sense and an antisense RNA strands form an
RNA duplex; and

degrading the human C3 regulatory mRNA wherein degrading the
human C3 regulatory mRNA inhibits expression of the human C3 regulatory
mRNA, inhibits initiation of a complement system response, inhibits
proliferation of a complement system response, or any combination thereof.
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Examiner’s Rejections
1. Claims 24, 25, 27–29, 34, 35, 37, 40, 41, 43, 46–48, 50, 53, and 54
stand rejected under 35 U.S.C. § 103(a) as unpatentable over Ambati2 and
Khvorova.3 (Ans. 5.)
2. Claims 26, 30, and 31 stand rejected under 35 U.S.C. § 103(a) as
unpatentable over Ambati, Khvorova, and Tolentino.4 (Id. at 14.)
3. Claim 45 stands rejected under 35 U.S.C. § 103(a) as unpatentable
over Ambati, Khvorova, and Yamagami.5 (Id. at 15.)
Appellants have presented arguments for the patentability of claims
24, 25, 27–29, 34, 35, 37, 40, 41, 43, 46–48, 50, 53, and 54 as a group.
(Appeal Br. 6–13.) Therefore, we limit our discussion to claim 24 as
representative of those claims.
FINDINGS OF FACT
We adopt the Examiner’s findings and analysis concerning the scope
and content of the prior art. The following findings are included for
emphasis and reference convenience.
FF 1. The Examiner finds that Ambati teaches methods of treating age-
related macular degeneration through intravitreal injection of inhibitors
(including siRNAs) of complement C3a, and that C3a is an activated form of
C3. (Ans. 6, citing Ambati, Title; Abstract; ¶¶ 8, 9, 42, 62, and claim 3.)

2 Ambati, US 2006/0067935 A1, published Mar. 30, 2006 (“Ambati”).
3 Khvorova et al., US 2005/0255487 A1, published Nov. 17, 2005
(“Khvorova”).
4 Tolentino et al., US 2004/0018176 A1, published Jan. 29, 2004.
5 Yamagami et al., Cytokine Profiles of Aqueous Humor and Graft in
Orthotopic Mouse Corneal Transplantation, 66 TRANSPLANTATION 11,
1504–10 (1998).
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FF 2. The Examiner finds that the only mRNA that encodes C3a is the C3
mRNA. (Id. at 6–7.)
FF 3. The Examiner finds that Khvorova teaches an algorithm for
generating highly functional siRNAs, and that the algorithm has been
applied to the entire human genome with the output organized by gene name
and NCBI6 Accession number in Tables XII and XIII. (Id. at 7, citing
Khvorova, ¶¶ 482, 483.)
FF 4. The Examiner finds that one of ordinary skill in the art would have
been able to easily locate siRNA sense strands for complement C3 by
searching Tables XII and XIII of Khvorova for either “C3” or its GenBank
Accession “NM_000064.1.” (Id.)
FF 5. The Examiner finds that Tables XII and XIII of Khvorova disclose
about 100 and about 85 C3 siRNA sense strands, respectively, and that
Table XIII discloses SEQ ID NO: 2222524, which is identical to nucleotides
3–21 of the claimed SEQ ID NO: 45. The Examiner provides the alignment
below where Qy is SEQ ID NO: 45 and Db is Khvorova SEQ ID NO:
2222524.

(Id. at 7–8.)

6 NCBI stands for The National Center for Biotechnology Information.
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ISSUE
Whether a preponderance of evidence of record supports the
Examiner’s conclusion of obviousness with respect to claim 24.
ANALYSIS
Rejection No. 1
The Examiner concluded that it would have been obvious to one of
ordinary skill in the art to use any of the C3 siRNAs of Khvorova to inhibit
expression of C3 as suggested by Ambati, and that it would have been
obvious to select SEQ ID NO: 2222524 as an siRNA sense strand because it
represents a single embodiment from a finite group of alternatives disclosed
by Khvorova. (Ans. 8; see also FF 1–5.) The Examiner also concluded that
one of skill in the art would have had a reasonable expectation that any of
the C3 siRNAs disclosed in Khvorova Tables XII and XIII would have been
functional, and would have therefore inhibited C3 and C3a expression in the
method of Ambati. (Ans. 8–13.)
We find that the Examiner has satisfied the burden of showing “some
articulated reasoning with some rational underpinning to support the legal
conclusion of obviousness.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398,
418 (2007). Moreover, the Examiner has established a prima facie case of
obviousness and, as discussed below, Appellants have not overcome that
prima facie case.
Number of Sequences in Khvorova
Appellants argue that “Khvorova discloses over 1.5 million
(>1,500,000) siRNA molecules” and that “[p]icking one sequence out of a
group of over 1.5 million would be analogous to finding a needle in a
haystack.” (Appeal Br. 9.) Appellants further argue that “the Office has not
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explained how one of skill in the art would have been led to SEQ ID NO: 45
when faced with over 1.5 million choices.” (Id.)
We are not persuaded by Appellants’ arguments. As explained by the
Examiner, Khvorova shows that one of ordinary skill would have been able
to select C3 siRNAs from about 185 examples in order to form a pool of
inhibitory C3 siRNAs for use in the method of Ambati. (FF 3–5; Ans. 16–
17.) Moreover, the fact that Khvorova discloses approximately 185
inhibitory C3 siRNA sequences does not overcome a conclusion of
obviousness. See Merck & Co., Inc. v. Biocraft Labs, Inc., 874 F.2d 804,
807 (Fed. Cir. 1989) (“That the [prior art] patent discloses a multitude of
effective combinations does not render any particular formulation less
obvious”).
Appellants also argue that the claims are nonobvious based on a lead
compound analysis. (Appeal Br. 9–13.) In particular, Appellants argue that
“Khvorova is a general application with millions of leads. There is no
guidance from Khvorova on how to select the lead.” (Id. at 9.) Even if we
assume that a lead compound analysis is appropriate on these facts, we are
not persuaded by Appellants’ arguments.
The lead compound inquiry begins with “whether a chemist of
ordinary skill would have selected the asserted prior art compounds as lead
compounds, or starting points, for further development efforts.”7 Otsuka

7 The second part of the obviousness inquiry is “whether the prior art would
have supplied one of ordinary skill in the art with a reason or motivation to
modify a lead compound to make the claimed compound with a reasonable
expectation of success.” Otsuka, 678 F.3d at 1292. Here, of course,
Appellants are not claiming a new compound or modification of a lead
compound.
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Pharm. Co., Ltd. v. Sandoz, Inc., 678 F.3d 1280, 1291 (Fed. Cir. 2012).
Furthermore, the lead compound analysis “is guided by evidence of the
compound’s pertinent properties.” Id. at 1292. Here, Khvorova discloses
about 185 “lead compounds” or starting points that have the pertinent
property of inhibiting C3. (FF 4, 5.) Appellants’ lead compound argument
is unpersuasive.
C3a versus C3
Appellants argue that the Office has not explained why one of skill in
the art would have substituted the target of Ambati (C3a) with the claimed
target (C3), arguing further that “C3a and C3 are not the same or identical
target.” (Appeal Br. 9.) We are not persuaded by Appellants’ argument.
The Examiner explained in detail why “one of ordinary skill would have
immediately realized that, in order to use siRNA to inhibit C3a as suggested
by Ambati, one would make siRNA that recognized C3 mRNA.” (Ans. 6.)
For example, the Examiner explained that “one of ordinary skill . . . would
have targeted the C3 mRNA because there is no other mRNA that encodes
C3a. Therefore, no substitution of a target was necessary.” (Id. at 17.)
We recognize, but find unpersuasive, Appellants reply argument that
the Examiner did not provided any evidence to support his explanation of
the relationship of C3 and C3a. (Reply Br. 2–3.) However, the
establishment of a prima facie case of obviousness, as the Examiner has
done here, shifts the burden of producing contrary evidence or arguments to
Appellants. See In re Best, 562 F.2d 1252, 1254–55 (CCPA 1977); In re
Oetiker, 977 F.2d 1443, 1445–46 (Fed. Cir. 1992).

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Reasonable Expectation of Success
Appellants argue that the Examiner “fails to provide sufficient
evidence that one of skill in the art would have had a reasonable expectation
of success in using SEQ ID NO: 45 in the presently claimed methods.”
(Appeal Br. 12.) In advancing this argument, Appellants state that
“Khvorova’s algorithm does not tell the skilled artisan the sequences that
will work or be reasonably expected to succeed.” (Id.) Appellants also
point to Figure 10b of Khvorova as showing that some siRNAs do not work,
and to Figure 15 as showing that “some of the siRNAs actually increase
expression.” (Id. at 12–13.) Appellants also argue that “the Office must
show that there is a reasonable expectation of success with regards to the
specific sequence identifiers, not just siRNA in general.” (Reply Br. 4.)
Appellants’ arguments regarding a reasonable expectation of success
are unpersuasive. The Examiner addresses Khvorova’s algorithm and
Figures 10 and 15 in explaining why “even a randomly chosen siRNA is
more likely than not to have inhibitory activity, and that siRNAs developed
by the algorithm of Khvorova are even more likely to be highly functional
than are randomly chosen ones.” (Ans. 8–13, 19–21.) Thus, based on the
teachings of Khvorova, one of skill in the art would have had a reasonable
expectation that any of the C3 siRNAs disclosed in Khvorova Tables XII
and XIII (including SEQ ID NO: 2222524) would have been functional, and
would have inhibited C3 and C3a expression in the method of Ambati.
(Ans. 11.) Indeed, to hold otherwise would mean that the use of any of the
siRNAs disclosed by Khvorova would be separately patentable simply
because their respective properties must be verified through testing. See
Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364 (Fed. Cir. 2007).
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CONCLUSION OF LAW
A preponderance of evidence of record supports the Examiner’s
conclusion that claim 24 is obvious under 35 U.S.C. § 103(a). Claims 25,
27–29, 34, 35, 37, 40, 41, 43, 46–48, 50, 53, and 54 were not argued
separately and therefore fall with claim 24.
Rejections 2 and 3
Appellants make no substantive arguments regarding the rejections of
claims 26, 30, 31, and 45. (Appeal Br. 14–15.) Instead, Appellants rely on
their arguments regarding claim 24, and further argue that, as dependent
claims, claims 26, 30, 31, and 45 are nonobvious if their respective
independent claims are nonobvious. (Id.) Since their respective
independent claims are obvious, we affirm these rejections as well. See
Hyatt v. Dudas, 551 F.3d 1307, 1314 (Fed. Cir. 2008).
CONCLUSION OF LAW
A preponderance of evidence of record supports the Examiner’s
conclusion that claims 26, 30, 31, and 45 are obvious under 35 U.S.C.
§ 103(a).
SUMMARY
We affirm the rejections of all claims on appeal.

No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED