Ex Parte Cosenza

Board of Patent Appeals and Interferences

Nov 30, 2010

10735203 (B.P.A.I. Nov. 30, 2010)

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.
10/735,203 12/12/2003 Lawrence W. Cosenza DSI-10402/22 2593
25006 7590 11/30/2010
GIFFORD, KRASS, SPRINKLE,ANDERSON & CITKOWSKI, P.C
PO BOX 7021
TROY, MI 48007-7021
EXAMINER
WEHBE, ANNE MARIE SABRINA
ART UNIT PAPER NUMBER
1633
MAIL DATE DELIVERY MODE
11/30/2010 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 BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte LAWRENCE W. COSENZA
__________

Appeal 2010-008654
Application 10/735,203
Technology Center 1600
__________

Before DONALD E. ADAMS, ERIC GRIMES, and STEPHEN WALSH,
Administrative Patent Judges.

WALSH, Administrative Patent Judge.

DECISION ON APPEAL1
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
therapeutic delivery system and to an organism for delivery of a therapeutic
agent. The Patent Examiner rejected the claims as failing to comply with the

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, or for filing a request for rehearing,
as recited in 37 C.F.R. § 41.52, begins to run from the “MAIL DATE”
(paper delivery mode) or the “NOTIFICATION DATE” (electronic delivery
mode) shown on the PTOL-90A cover letter attached to this decision.

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written description requirement and the enablement requirement. We have
jurisdiction under 35 U.S.C. § 6(b). We affirm.
STATEMENT OF THE CASE
Claims 1-2, 4, 7-8, 11, and 41 are on appeal. Claim 1 is representative
and reads as follows:
1. A therapeutic delivery system for a host comprising:
a therapeutic agent; and
a sacromastigophoric [sic2] organism containing said therapeutic agent
through packaging and a gene encoding full length primate Hpr; said gene
further comprising an inducible promoter and encoding a lysosomal
targeting sequence.3

(Emphasis added to highlight the main dispute.)
The Examiner rejected the claims as follows:
• claims 1-2, 4, 7-8, 11, and 41 under 35 U.S.C. § 112, first
paragraph, as failing to comply with the written description requirement; and
• claims 1-2, 4, 7-8, 11, and 41 under 35 U.S.C. § 112, first
paragraph, as failing to comply with the enablement requirement.

2 Appellant refers to the organism as sacromastigophoric, but does not
define the term. That term does not appear to be used in the art. The art
classifies Appellant’s preferred organisms, trypanosomes, in the phylum
“sarcomastigophora,” “a phylum of protozoans that includes forms moving
by flagella, pseudopodia, or both and that is divided into the subphyla
Mastigophora and Sarcodina.” See e.g., www.merriam-
webster.com/medical/sarcomastigophora, last visited Nov. 10, 2010.
3 In response to a restriction requirement, Appellant elected without traverse
a therapeutic delivery system comprising a drug or prodrug, the species
Trypanosome as the organism, and Hpr as the lytic factor. (See Ans. 3;
Reply 1.)
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WRITTEN DESCRIPTION
The Issue
The Examiner’s position is that the Specification does not provide
sufficient written description for claim 1’s genus “a gene encoding full
length primate Hpr protein.” (Ans. 5.) The Specification identifies “Hpr” as
haptoglobin-related protein, a serum factor said to induce lysis of the
parasite Trypanosoma brucei brucei. (Spec. 4, ll. 3-16.) The Examiner
found that “aside from the human Hpr cDNA sequence and encoded amino
acid sequence, the specification does not provide any additional description
for any other Hpr genes or proteins from any other primate species.” (Ans.
5.) The Examiner found that the primate genus is large, comprising more
than 200 species. (Id.) However, the Examiner found that at the time of
filing “the prior art did not teach a single functional non-human primate Hpr
gene.” (Id.) According to the Examiner, Smith4 taught that “in non-human
primates the only known Hpr gene is found in Chimpanzees, where the gene
does not express functional protein due to premature termination of
translation.” (Id.) Further, the Examiner found that neither the Specification
nor the prior art taught, suggested, or exemplified the level of sequence
and/or structural homology or shared common structures between primate
Hpr genes, nor identified a non-human primate species possessing a
functional Hpr gene. (Id. at 5-6.)
Appellant contends that the disclosure of a complete nucleic acid
sequence for human Hpr in its Application “provides sufficient written
description of recombinant Hpr.” (App. Br. 8.) According to Appellant,

4 Andrea B. Smith et al., Killing of Trypanosomes by the Human
Haptoglobin-Related Protein, 268 SCIENCE 284-286 (1995).
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“only humans, baboons, and chimpanzees possess full length Hpr [and]
these Hpr genes possess high sequence homology.” (Id. at 9.) Therefore,
Appellant asserts that “[t]he description by nucleotide and amino acid
sequence of the cDNA for Hpr recites ‘structural features common to the
members of the genus’ given the high homology between the Hpr genes in
primates.” (Id., quoting Regents of the Univ. of Calif. v. Eli Lilly & Co., 119
F.3d 1559, 1569 (Fed. Cir. 1997)). Additionally, Appellant asserts that the
disclosure of the nucleotide and amino acid sequences identifies “features
[that] constitute a substantial portion of the genus” which, according to
Appellant, has only three members. (Id.) Appellant also asserts that “the
recitation of the term Hpr is sufficient to describe the Hpr genes expressed in
primates.” (Id. at 10, citing Bigham v. Godtfredsen, 857 F.2d 1415, 1417
(Fed. Cir. 1988) (“[t]he generic term halogen comprehends a limited number
of species, and ordinarily constitutes a sufficient written description of the
common halogen species.”)).
The issue with respect to this rejection is whether the Examiner
established that a person of ordinary skill in the art would not credit
Appellant with possession of a genus of genes encoding full length primate
Hpr protein.
Findings of Fact
1. We agree with the Examiner’s explicit findings regarding the scope
and content of (1) the Specification, and (2) the Smith paper. (See Ans. 5-
13.)
2. Smith disclosed:
[t]he haptoglobin-related protein is the product of a gene
triplication event that occurred in apes and Old World monkeys
early in primate evolution, resulting in the haptoglobin gene,
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the haptoglobin-related gene and the primate haptoglobin gene
(20). In humans, a subsequent homologous unequal crossover
took place, leaving the original haptoglobin gene and producing
the human haptoglobin-related gene, a hybrid of the
haptoglobin-related gene and the primate haptoglobin gene. In
nonhuman primates, the sequence of the haptoglobin-related
protein is known only for chimpanzees, where a frameshift
leads to premature termination of translation (20). The absence
of intact haptoglobin-related protein in chimpanzees is
consistent with their lack of TLF [trypanosome lytic factor]
activity and may explain why the primate most related to
humans does not have this protective mechanism (19).

(Smith, 285-86.)
Principles of Law
When an Applicant claims a class, the Applicant “must describe that
class in order to meet the description requirement of the statute.” In re
Lukach, 442 F.2d 967, 968 (CCPA 1971). “The adequate written description
requirement . . . serves ‘to ensure that the inventor had possession, as of the
filing date of the application relied on, of the specific subject matter later
claimed by him; how the specification accomplishes this is not material.’”
In re Alton, 76 F.3d 1168, 1172 (Fed. Cir. 1996) (citation omitted).
Analysis
Independent claims 1 and 11 recite “a gene encoding full length
primate Hpr” and independent claim 41 recites “a gene encoding primate
Hpr.” Appellant does not dispute that the primate genus comprises more
than 200 species. However, according to Appellant “only humans, baboons,
and chimpanzees possess full length Hpr [and] these Hpr genes possess high
sequence homology.” (App. Br. 9). For support, Appellant refers to the
Specification at 34, ll. 16-17, which reads: “[a] clone containing the known
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Hpr gene coding sequence (SEQ ID NO. 28) has been generated as shown in
Figure 11.” Neither this statement, nor Figure 11 evidences that the total
number of species with full-length primate Hpr genes is three, as Appellant
argues. Further, the Specification does not evidence the alleged “high
degree of sequence identity between members of the genus of primate Hpr
genes.”
The Examiner provided evidence that Appellant’s arguments about
other primate Hpr proteins are mistaken. Contrary to Appellant’s argument,
Smith disclosed that the chimpanzee has an Hpr gene, but that the gene does
not encode full length Hpr. (Ans. 5; FF-2.) Appellant offers no evidence to
support the attorney argument that baboons and chimpanzees possess full
length Hpr with high sequence homology to human Hpr. (App. Br. 9.) The
Examiner referred particularly to Smith at 285-86, which explicitly stated
that “[i]n nonhuman primates, the sequence of the haptoglobin-related
protein is known only for chimpanzees.” (FF-2, emphasis added.) Smith is
direct evidence contrary to Appellant’s generalized allegations that a person
of skill in the art would take the human protein as representative of other
primate Hpr proteins. Consequently, we find that the Examiner provided
sufficient evidence that a person of ordinary skill in the art would not credit
Appellant with possession of the genus “a gene encoding full length primate
Hpr” recited in the claims.
ENABLEMENT
The Issue
The Examiner’s position is that the Specification does not provide an
enabling disclosure for: (1) making and using a Trypanosome (the disclosed
representative sacromastigophoric organism) containing a gene or a cDNA
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encoding non-human primate Hpr; (2) delivering a drug or prodrug by lysing
any species of Trypanosome containing the drug through expression of
human Hpr; and (3) packaging a drug or prodrug in a Trypanosome as
claimed for use as a drug delivery system. (Ans. 8.) According to the
Examiner, based upon the state of the art, the limited guidance in the
Specification, and the breadth of the claims, a skilled artisan would need to
perform undue experimentation to make and use the claimed therapeutic
delivery system. (Id. at 9-13.)
Appellant contends that the instant “specification teaches how a gene
encoding Hpr is operative to lyse Trypanosomes as claimed in the subject
invention.” (App. Br. 12.) According to Appellant, the Specification
explains that “[t]he inventive organism constitutively expresses TetR that
represses expression of the Hpr gene… [and i]ntroduction of the inducer
tetracycline removes TetR from the promoter removing the repression and
allowing selectively timed expression of the Hpr gene leading to lysis of the
organism.” (Id.) Appellant thus argues that the Examiner’s concern with
endocytosis is misplaced. (Id. at 13-14.)
Addressing the Examiner’s concern with the scope of the genus of full
length Hpr genes and proteins, Appellant repeats the arguments used to
address the written description rejection. (Id. at 14-15.) Addressing the
Examiner’s concern with packaging drugs into trypansomes, Appellant
argues that Specification Examples 1-3 are sufficient guidance to practice
the invention. (Id. at 16-17.)
The issues with respect to this rejection are whether the evidence
supports the conclusions that undue experimentation would be required to
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(1) make and use a Trypanosome containing a gene encoding a non-
human primate Hpr;
(2) deliver a drug or prodrug by lysing any species of Trypanosome
containing the drug through expression of human Hpr; and
(3) package a drug or prodrug in a Trypanosome as claimed for use as
a drug delivery system.
Additional Findings of Fact
3. Smith disclosed: “[t]he involvement of the haptoglobin-related
protein in TLF-mediated lysis is consistent with the observation that only
some apes and Old World monkeys have lytic activity in their serum.”
(Smith 285.)
4. Shimamura5 stated: “The ability of [Trypanosoma brucei] rhodesiense
to infect humans may be due to reduced endocytosis of [Trypanosome lytic
factor-1] and failure to enter the lysosome.” (Shimamura 227.)
Principles of Law
“[T]o be enabling, the specification of a patent must teach those
skilled in the art how to make and use the full scope of the claimed invention
without ‘undue experimentation.”’ Genentech, Inc. v. Novo Nordisk, A/S,
108 F.3d 1361, 1365 (Fed. Cir. 1997) (quoting In re Wright, 999 F.2d 1557,
1561 (Fed. Cir. 1993)). The Examiner has the initial burden to establish a
reasonable basis to question the enablement provided for the claimed
invention. Wright at 1562. “Even if some of the claimed combinations were

5 Masako Shimamura et al., The lysosomal targeting and intracellular
metabolism of trypanosome lytic factor by Trypanosoma brucei brucei, 115
MOLEC. & BIOCHEM. PARASITOLOGY 227-237 (2001).
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inoperative, the claims are not necessarily invalid. . . .” Atlas Powder Co. v.
E.I. Du Pont De Nemours & Co., 750 F.2d 1569, 1576 (Fed. Cir. 1984).
Analysis
(1) Making and using a trypanosome containing a gene encoding a non-
human primate Hpr.

We have considered the evidence proffered by the Examiner, but do
not find that the Examiner met the burden of establishing a reasonable basis
to question the enablement provided for the claimed invention. Wright, 999
F.2d at 1562. In particular, we do not find that the Examiner has established
that a skilled artisan would have had to perform undue experimentation to
find and use the gene for lytic Hpr from other primates. Smith confirms that
lytic activity is present in some apes and Old World monkeys. (FF-3.) With
respect to isolating primate species of Hpr gene other than human Hpr, we
agree with Appellant that methods of sequencing genes were well known
and well established in the art at the time of filing. (See App. Br. 15.) The
Examiner has not established that a skilled artisan at the time of the
invention would not have been able to apply the knowledge in the art, along
with the instant disclosure to similarly identify, isolate and sequence a non-
human Hpr gene having the required lytic function. Further, with respect to
using the non-human Hpr, as Appellant has explained, the instant
Specification provides working examples demonstrating how to prepare a
Trypanosome with an inducible gene encoding full length Hpr comprising
an inducible promoter and encoding a lysosomal targeting sequence. (See
id. at 17.) We conclude that the rejection provides insufficient evidence to
show that the experimentation needed would be undue.
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(2) Delivering a drug or prodrug by lysing any species of Trypanosome
containing the drug.

With respect to lysing any species of Trypanosome through
expression of Hpr, we agree with Appellant that the Specification provides
sufficient guidance by teaching how the expression of a gene encoding Hpr
that is under the control of a Tet inducible promoter is operative to lyse
Trypanosomes. (See App. Br. 12.) We do not share the Examiner's opinion
that Shimamura established a reasonable basis to question the enablement
for the claimed invention. According to the Examiner, “the prior art is clear
that human Hpr is not active as a lytic agent against all species of
Trypanosome….” (Ans. 10-11.) Specifically, the Examiner found that
Shimamura taught “that Trypanosoma brucei rhodensiense [sic] is not lysed
by Hpr or the TLF [Trypanosome lytic factor] complex comprising Hpr.”
(Id. at 11.) However, we agree with Appellant that Shimamura explained
that the reason that Trypanosoma brucei rhodesiense is not lysed by Hpr
may be due to the reduced endocytosis of TLF/Hpr. (App. Br. 14; FF-2.)
As Appellant explains, the invention does not require endocytosis for lysis,
as the Hpr is produced within the Trypanosome itself. (Id. at 13.) Put
another way, because Shimamura discusses endocytosis of TLF/Hpr, it does
not weigh against enablement for Appellant’s delivery method that does not
involve endocytosis of TLF/Hpr. We conclude that the weight of the
evidence concerning lysis is insufficient to support a conclusion of undue
experimentation regarding that issue.
(3) Packaging a drug or prodrug.
The Examiner acknowledged that the Specification explained that
“[n]on-nucleic acid therapeutic agents are packaged in a sacromastigophoric
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organism through electroporation or phagocytosis of liposomally packaged
therapeutic agents.” (Ans. 12.) The Examiner also acknowledged that the
Specification referenced three US Patents “as providing guidance for
liposomal packaging processes or electroporation.” (Id.) However, the
Examiner found that “[n]either the Specification nor the prior art teach that
drugs, either packaged in a liposome … or not, can be introduced and stably
maintained in a Trypanosome, or subsequently released to a host organism
upon lysis of the Trypanosome,” and concluded that a skilled artisan would
require undue experimentation to make and use the claimed delivery system.
(Id.) What is missing from the Examiner’s case is evidence that a skilled
artisan would have required further guidance to incorporate a drug or
prodrug, packaged according to prior art methods, into a well-characterized
Trypanosome. See Wright, 999 F.2d at 1562. We conclude that the weight
of the evidence concerning drug packaging is insufficient to support a
conclusion of undue experimentation regarding that issue.
In sum, we reverse the enablement rejection because there is
insufficient evidence to conclude that the full scope of “a gene encoding full
length primate Hpr” is not enabled.
CONCLUSIONS OF LAW
The Examiner established that a person of ordinary skill in the art
would not credit Appellant with possession of the claimed invention.
We conclude there is insufficient evidence to support the enablement
rejection.
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SUMMARY
We affirm the rejection of claims 1-2, 4, 7-8, 11, and 41 under
35 U.S.C. § 112, first paragraph, for failing to comply with the written
description requirement.
We reverse the rejection of claims 1-2, 4, 7-8, 11, and 41 under
35 U.S.C. § 112, first paragraph, for failing to comply with the enablement
requirement.
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

lp

GIFFORD, KRASS, SPRINKLE,ANDERSON & CITKOWSKI, P.C
PO BOX 7021
TROY MI 48007-7021