Ex Parte Schaffer et al

Patent Trial and Appeal Board

Jun 17, 2016

10880297 (P.T.A.B. Jun. 17, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
10/880,297 06/28/2004
84220 7590 06/21/2016
UC Berkeley - 01L
Bozicevic, Field & Francis LLP
1900 University Avenue, Suite 200
East Palo Alto, CA 94303
FIRST NAMED INVENTOR
David V. Schaffer
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
BERK-024 8653
EXAMINER
HIBBERT, CATHERINE S
ART UNIT PAPER NUMBER
1636
NOTIFICATION DATE DELIVERY MODE
06/21/2016 ELECTRONIC
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.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address( es):
docket@bozpat.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte DAVID V. SCHAFFER,
BRIAN KASPAR, and NARENDRA MAHESHRI
Appeal2013-007513
Application 10/880,297
Technology Center 1600
Before DONALD E. ADAMS, ERIC B. GRIMES, and
JACQUELINE T. HARLOW, Administrative Patent Judges.
ADAMS, Administrative Patent Judge.
DECISION ON APPEAL 1
This appeal under 35 U.S.C. § 134(a) involves claims 11, 29, 33, 36-
43, and 45--48 (App. Br. 3). 2 Examiner entered rejections under 35 U.S.C.
§ 102(b) and 35 U.S.C. § 103(a). We have jurisdiction under 35 U.S.C.
§ 6(b).
We REVERSE.
1 Appellants identify the Real Party in Interest as "The Regents of the
University of California" (App. Br. 3).
2 Examiner states that claims 47 and 48 are allowable (Ans. 4).
Appeal2013-007513
Application 10/880,297
STATEMENT OF THE CASE
The claims are directed to an infectious recombinant adeno-associated
virus (rAA V) virion" (see e.g., Appellants' claim 11 ). Claim 11 is
representative and reproduced in the Claims Appendix of Appellants' Brief.
Claims 11 and 36-42 stand rejected under 35 U.S.C. § 102(b) as
anticipated by Wu. 3
Claims 11, 29, 33, 36-43, 45, and 46 stand rejected under 35 U.S.C.
§ 103(a) as unpatentable over the combination of Xie, 4 Wu, Fosnaugh, 5
Rabinowitz '907, 6 Rabinowitz '004, 7 Bartlett, 8 Samulski, 9 and Shi. 10
Anticipation:
ISSUE
Does the preponderance of evidence on this record support
Examiner's finding that Wu teaches Appellants' claimed invention?
3 Pei Wu et al., Mutational Analysis of the Adena-Associated Virus Type 2
(AA V2) Capsid Gene and Construction of AAV2 Vectors with Altered
Tropism, 74(18) J. Virology 8635-8647 (2000).
4 Qing Xie et al., The atomic structure of adeno-associated virus (AA V-2), a
vector for human gene therapy, 99(16) PNAS 10405-10410 (2002).
5 Fosnaugh et al., US 2003/0143732 Al, published July 31, 2003.
6 Rabinowitz et al., US 6,491,907 Bl, issued Dec. 10, 2002.
7 Rabinowitz et al., WO 00/28004, published May 18, 2000.
8 Bartlett, US 2002/0192823 Al, published Dec. 19, 2002.
9 Samulski et al., US 2002/0136710 Al, published Sept. 26, 2002.
10 Wenfang Shi et al., Capsid modifications overcome low heterogeneous
expression of heparan sulfate proteoglycan that limits AA V2-mediated gene
transfer and therapeutic efficacy in human ovarian carcinoma, 103
Gynecologic Oncology 1054--1062 (2006).
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Appeal2013-007513
Application 10/880,297
FACTUAL FINDINGS (FF)
FF 1. Examiner finds that Wu discloses a rAA V "virion product
comprising heterologous nucleic acid and a variant AA V capsid protein,"
specifically Wu's mutant 32, which "comprises at least one amino acid
substitution[, in a surface accessible region of the GH loop of the capsid,]
relative to a wild-type AA V capsid protein" and is, according to Wu, a Class
1 viable mutant (Ans. 7 (emphasis removed), citing Wu 8637, Figure 1,
Loop IV mutant 32 and associated table; see also Wu Abstract (Class 1
mutants [are] viable"); Ans. 8-9; see also Ans. 45).
FF 2. Examiner finds that while Wu "does not disclose methods of testing
each mutant in primary non-permissive cells specifically using methods
wherein infectivity is expressed as the ratio of infectious viral particles to
total viral particles" this requirement of Appellants' claimed invention is
nothing more than "a description of a characteristic/property of the claimed
pro[duct]" (Ans. 7-8; cf Appellants' claim 11).
ANALYSIS
The infectious recombinant rAA V virion of Appellants' claim 11
comprises: (a) a variant AA V capsid protein that comprises at least one
amino acid substitution, in a surface accessible region of the GH loop of the
capsid, relative to a wild-type AA V capsid protein and (b) a heterologous
nucleic acid (see Appellants' claim 11). Appellants' claim 11 further
requires that: (1) the at least one amino acid substitution results in increased
infectivity of a non-permissive primary cell compared to the infectivity of a
wild-type AA V virion for the non-permissive cell and (2) infectivity is
expressed as the ratio of infectious viral particles to total viral particles (id.).
Appellants' claims 36-42 depend directly from Appellants' claim 11.
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Application 10/880,297
Examiner finds that Wu "meets all of the structural limitations of the
[]claimed product of claim 11" (Ans. 9; see FF 1-2). We are not persuaded.
As Appellants explain, Wu's "mutant 32 ... ha[s] a 'wild-type'
phenotype" (Reply Br. 3, citing Wu 8639: Table 1; see also Wu 8637 Figure
1 and associated table). We recognize, but are not persuaded by, Examiner's
assertions that Appellants'
argument that the mutants of Wu [] do not necessarily exhibit
increased infectivity in a non-permissive cell relative to a wild-
type AA V virion [] does not provide evidence or proof that the
virions of Wu [] were incapable of increased [infectivity] of a
non-permissive primary cell compared to a wild-type AA V
v1non
and "products are not usually severed from their properties" (Ans. 40-41
and 43). As Examiner recognizes, however, Wu "shows that [the] mutant 32
is a Loop 4 mutant that is infectious (i.e., has the primary phenotype of wild-
type") (Ans. 38 (emphasis removed)). What is missing on this record is an
evidentiary basis to support a finding that Wu's "mutant 32 exhibits
increased infectivity of a non-permissive cell, as required by" Appellants'
invention (Reply Br. 3).
CONCLUSION OF LAW
The preponderance of evidence on this record fails to support
Examiner's finding that Wu teaches Appellants' claimed invention. The
rejection of claims 11 and 36-42 under 35 U.S.C. § 102(b) as anticipated by
Wu is reversed.
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Application 10/880,297
Obviousness:
ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness?
FACTUAL FINDINGS (FF)
FF 3. Examiner finds that the combination of Xie, Wu, and Bartlett fails to
suggest "a heterologous nucleic acid encoding [] an RNAi" and relies on
Fosnaugh to disclose the use of "viral vectors to express siRNA or RNAi to
cells or organism[ s] for therapeutic, diagnostic, target violation, [sic,
validation?] etc." (Ans. 16).
FF 4. Examiner finds that the combination of Xie, Wu, Bartlett, and
Fosnaugh fails to suggest "a non-permissive cell which is a stem cell or
more specifically a neural stem cell" and relies upon Rabinowitz '907 to
disclose the use of "AAV virus to carry [a] heterologous gene into cells as
well as altering the tropism of AA V so that they can infect various cell
types" (Ans. 17; see id. (wherein Examiner relies on Rabinowitz '004 to
disclose rAA V "virions, comprising a foreign nucleic acid sequence").
FF 5. Examiner relies on Samulski to suggest "methods for increasing
infection by AA V or changing from a non-permissive to a permissive
tropism for AA V, for example by mutating the capsid" (Ans. 17).
FF 6. Examiner relies on Shi to disclose "altered AA V virion tropism
caused by genetically modified capsid" (Ans. 18).
ANALYSIS
Based on the combination of Xie, Wu, Fosnaugh, Rabinowitz '907,
Rabinowitz '004, Bartlett, Samulski, and Shi, Examiner concludes that, at
the time Appellants' invention was made, it would have been prima facie
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Application 10/880,297
obvious "to have made substitution mutations in surface accessible regions
of the GH loop, as disclosed in Xie []and Wu[] for the purpose of altering
tropism and increasing infection efficiencies for the rationale of making
better gene therapy vectors" (Ans. 18). In this regard, Examiner concludes
that in view of the combination of Xie, Wu, and Bartlett, a person of
ordinary skill in this art would have found it prima facie obvious "to have
substituted at least one amino acid in the relatively small region of the
critical GH loop of an AA V capsid protein," because Xie, Wu, and Bartlett
disclose the AA V capsid sequence and provide "routine methods for making
and assaying such mutations," including "GH loop regions important for
tropism, escaping immune response, and infectivity" (id.). Further,
Examiner concludes that
(id.).
it would have been further obvious in view of the references of
Rabinowitz[,] Samulski[,] and Shi [] to have made such mutants
for the purpose of infecting stem cells, including neural stem
cells, because these references suggest stem cells including
neural stem cells as a preferred embodiment of cell type
We recognize each of Appellants' contentions regarding the
combination of Xie, Wu, Fosnaugh, Rabinowitz '907, Rabinowitz '004,
Bartlett, Samulski, and Shi (see App. Br. 18--41; see generally Reply Br. 4;
see also Ans. 29--47). In this regard, Appellants contend that "Xie does not
'explicitly point to any amino acids in the GH loop regions important for
tropism, escaping immune response, and infectivity"' (App. Br. 19 and 20).
Appellants further contend that
while the amino acids noted in Xie to be involved in heparan
sulfate proteoglycan binding and noted in Table 1 of Wu are in
the GH loop, Wu reports that the mutants were non-infectious.
Thus, if anything, the combination of Xie and Wu teaches
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Application 10/880,297
away from making amino acid substitutions in the GH loop,
and therefore teaches away from the invention recited in
[Appellants' claims].
(App. Br. 21.) Appellants also contend that "[n]one of Fosnaugh,
Rabinowitz '907, Rabinowitz '004, Bartlett, Samulski, and Shi cures the
deficiencies of Xie, alone or in combination with Wu" (App. Br. 21
(emphasis removed)).
While Examiner recognizes Appellants' contentions, instead of
addressing Appellants' contentions in the context of what the combination of
references suggest as a whole, Examiner relies on Wu, maintaining that
Wu's "mutant 32[,] which is in the GH loop [] is infectious" (Ans. 47). For
the reasons set forth in the anticipation rejection, we are not persuaded that
Wu suggests Appellants' claimed invention. But for Examiner's reliance on
Wu, Examiner did not offer rebuttal arguments to Appellants' contentions
regarding the combination of Xie, Wu, Fosnaugh, Rabinowitz '907,
Rabinowitz '004; Bartlett; Samulski; and Shi (see App. Br. 18--41; see
generally Reply Br. 4; see also Ans. 29-47). Therefore, we are compelled to
reverse this rejection.
CONCLUSION OF LAW
The preponderance of evidence relied upon by Examiner fails to
support a conclusion of obviousness. The rejection of claims 11, 29, 33, 36-
43, 45, and 46 under 35 U.S.C. § 103(a) as unpatentable over the
combination of Xie, Wu, Fosnaugh, Rabinowitz '907, Rabinowitz '004,
Bartlett, Samulski, and Shi is reversed.
REVERSED
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