Ex Parte Harris et al

Patent Trial and Appeal Board

Jun 30, 2016

12622886 (P.T.A.B. Jun. 30, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
12/622,886 11120/2009 Reuben S. Harris
62274 7590 06/30/2016
DARDI & HERBERT, PLLC
Moore Lake Plaza, Suite 205
1250 East Moore Lake Drive
Fridley, MN 55432
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.
5054.04US04 5211
EXAMINER
HILL, KEVIN KAI
ART UNIT PAPER NUMBER
1633
MAILDATE DELIVERY MODE
06/30/2016 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 REUBENS. HARRIS, STEFAN R. JONSSON,
SCOTT C. FAHRENKRUG, and REBECCA ST. CLAIRE LARUE 1
Appeal 2014-005766
Application 12/622,886
Technology Center 1600
Before JEFFREY N. FREDMAN, JOHN G. NEW, and
JOHN E. SCHNEIDER, Administrative Patent Judges.
SCHNEIDER, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to using
cytosine deaminases to diminish retroelement transfer from pigs to humans,
which have been rejected as obvious. We have jurisdiction under 35 U.S.C.
§ 6(b).
We reverse.
1 Appellants identify the Real Party in Interest as Recombinetics, Inc.
Appeal Br. 3.
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Application 12/622,886
STATEMENT OF THE CASE
The invention relates to the use of cytosine deaminases to decrease the
ability of pigs and porcine cells to transmit porcine retroelements, such as
porcine endogenous retroviruses (PERVs) to non-porcine cells and tissues.
Spec. 1. A nucleic acid construct which expresses a non-porcine deaminase
is incorporated into a transgenic pig. The expression of the deaminase
decreases the ability of the porcine cell to transmit PER Vs to non-porcine
cells such as human cells. Spec. 2-3.
Claims 1, 2, 4--9, and 11 are on appeal. Claim 1 is illustrative and
reads as follows:
1. A transgenic pig, the nucleated cells of which
comprise a nucleic acid construct, said nucleic acid construct
comprising a transcriptional unit comprising a regulatory region
operably linked to a nucleic acid sequence encoding a non-
porcine APOBEC3 cytosine deaminase polypeptide.
The claims stand rejected as follows:
Claims 1, 2, 5-9, and 11 have been rejected under 35 U.S.C. § 103(a)
as unpatenable over Wells, U.S. 2005/0266561 Al (published Dec. 1, 2005)
("Wells"), in view ofMalim et al., U.S. 2004/0009951 Al (published Jan.
15, 2004) ("Malim"), Mangeat et al., Broad antiretroviral defence by human
APOBEC3G through lethal editing of nascent reverse transcripts, 424
Nature 99-103 (2003) ("Mangeat") and Pincus, Models of HIV infection
utilizing transgenic and reconstituted immunodeficient mice, 1 Drug
Discovery Today: Disease Models 49-56 (2004) ("Pincus").
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Application 12/622,886
Claim 4 has been rejected under 35 U.S.C. § 103(a) as unpatentable
over Wells in view of Malim, Mangeat, and Pincus in further view of
Hackett et al., U.S. 2004/0203158 Al (published Oct. 14, 2004) ("Hackett").
DISCUSSION (or I)
Issue
In rejecting the pending claims as obvious, the Examiner finds that
Wells discloses a transgenic pig whose genome comprises a heterologous
nucleic acid encoding transcriptional units comprising regulatory regions
operably linked to an interfering RNA (iRNA) molecule designed to inhibit
replication and/or expression of PER Vs. Ans. 2. The Examiner finds that
Malim discloses transgenic mammalian cells that comprise a nucleic acid
molecule that encodes for a non-porcine APOBEC3 cytosine deaminase. Id.
The Examiner finds that the deaminase disclosed in Malim inhibits
replication and/or expression of retroviruses such as HIV and MLV. Id.
The Examiner further finds the Malim reference teaches that the cytosine
deaminase provides a strategy for forming innate defense mechanism against
retroviral infection. Id. The Examiner finds that Mangeat discloses that
APOBEC3G confers antiviral activity on a broad range of retroviruses when
introduced into mammalian cells. Ans. 3. The Examiner finds that Pincus
"suggests the creation of transgenic animals comprising the human
APOBEC3G gene." Id. The Examiner concludes by concluding that
[i]t would have been obvious to one of ordinary skill in the art
to substitute a first transgene that inhibits retroviral infection
and/or replication, as disclosed by Wells, for a second transgene
that inhibits retroviral infection and/or replication, e.g.
APOBEC3G, as disclosed/taught by Malim et al, Mangeat et al
and Pincus, in a transgenic pig with a reasonable expectation of
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Appeal2014-005766
Application 12/622,886
success because the simple substitution of one known element
for another would have yielded predictable results to one of
ordinary skill in the art at the time of the invention .... An
artisan would be motivated to substitute a first transgene that
inhibits retroviral infection and/or replication for a second
transgene that inhibits retroviral infection and/or replication,
e.g. APOBEC3G, in a transgenic pig because prior to the
instant invention, those of ordinary skill in the art had
recognized the need to decrease or eliminate PERV infection of
human cells via xenotransplantation of porcine cells and/or
tissues (Wells), that human APOBEC3G is effective at
inhibiting a broad genus of retroviruses present in different
mammalian species and provides an effective mechanism of
promoting innate immunity against retroviruses (Malim et al,
Mangeat et al), that transgenic nonhuman cells and animals
routinely produced in the art include pigs, monkeys and non-
human primates, rats, mice and rabbits (Wells, [0076]; Malim
[0064]; Pincus) and Pincus suggest the creation of transgenic
animals comprising human APOBEC3G.
Ans. 3--4.
1A~ppellants contend that the references do not support the Examiner's
rationale for combining the references. Appeal Br. 7. Appellants contend
that Wells teaches suppressing protein expression whereas the instant
invention relies upon expression of the APOBEC protein. Appeal Br. 8.
Appellants argue that the combination of references would require a change
in the basic principles of the Wells reference. Id. Appellants also argue that
there is no reasonable expectation of success in that it was not known that
releasing cross-species APOBECs would not be lethal to the cell or
problematic for the viability of the cells as the endogenous viruses have
evolved to take on function within the host. Appeal Br. 8-9. Appellants
also argue that there is no motivation to combine the references. Id.
Appellants contend that Pincus, Malim, and Mangeat all relate to providing a
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Application 12/622,886
defense to infectious retroviruses and not endogenous retroviruses like
PERVs. Reply Br. 7-8.
The issue with respect to this rejection is whether the Examiner has
established by a preponderance of the evidence that the pending claims are
obvious over Wells combined with Malim, Mangeat, and Pincus as defined
by 35 U.S.C. § 103(a).
Findings of Fact
FF 1. Wells discloses a transgenic pig containing a nucleic acid
sequence coding for the expression of an iRNA molecule that inhibits the
expression and/or replication of PER Vs. Wells i-f 54.
FF2. Malim discloses transgenic mammalian cells with nucleic acids
sequences in an expression vector that encodes the APOBEC3 gene. Malim
,-r 64.
FF3. The APOBEC3 gene expressed in the cells of Malim are
designed to inhibit replication and/or expression of infectious retroviruses
such as HIV. Malim i-fi-18, 48, and 50.
FF4. Mangeat discloses "that APOBEC3G can act on a broad range
of retroviruses in addition to HIV, suggesting that hypermutation by editing
is a general innate defence mechanism against this important group of
pathogens." Mangeat 49.
FF5. Pincus suggests the creation of transgenic animal comprising the
human APOBEC3G gene as a mouse model of HIV infection. Pincus 50-
51.
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Appeal2014-005766
Application 12/622,886
Principles of Law
"[R ]ejections on obviousness grounds cannot be sustained by mere
conclusory statements; instead, there must be some articulated reasoning
with some rational underpinning to support the legal conclusion of
obviousness." KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007)
(quoting In re Kahn, 441F.3d977, 988 (Fed. Cir. 2006).
"Obviousness requires more than a mere showing that the prior art
includes separate references covering each separate limitation in a claim
under examination." Unigene Labs., Inc. v. Apotex, Inc., 655 F.3d 1352,
1360 (Fed. Cir. 2011). "Rather, obviousness requires the additional showing
that a person of ordinary skill at the time of the invention would have
selected and combined those prior art elements in the normal course of
research and development to yield the claimed invention." Id.
Analysis
Appellants have argued that the Examiner has not established a valid
rationale for combining the references. Appeal Br. 7-8; Reply Br. 6-8. We
agree. Malim, Mangeat, and Pincus teach the use of APOBEC3G to prevent
infection by a retrovirus by inserting the gene for APOBEC3G into a cell
that may become infected. FF3, 4, and 6. This is a completely different
approach than the instant invention where the gene is inserted in the
organism that may be the source of the retrovirus. Spec. 2. Nothing in the
references suggests insertion of the gene for APOBEC3G in a cell or
organism that contains an endogenous retrovirus. Appeal Br. 8. The
Examiner has not provided sufficient reason that would have lead one skilled
in the art to make the proposed combination.
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Application 12/622,886
The Examiner contends that the invention merely involves
substituting one gene for another and that both Wells and the present
invention relate to inhibiting the expression and/or replication of endogenous
retroviruses. Ans. 6-8. We are unpersuaded. While both Wells and the
instant invention relate to preventing infection by PERV s, their approaches
are different. Wells uses iRNA to prevent expression of proteins encoded by
the PERV s. FF 1. The instant invention calls for the expression of a protein
that in tum destroys the endogenous retrovirus. Spec. 2. The Examiner has
not established that the two approaches are equivalent, nor has the Examiner
provided sufficient logic that the ordinary artisan would have expected the
APOBEC3G enzyme to be effective against PERVs.
The secondary references do not provide the required motivations.
The references only address use of the deaminases against infectious
retroviruses such as HIV. FF 3 and. Nothing in the references suggests that
deaminases would have been expected to be effective against endogenous
retrovirus, and particularly PERV s. We agree with Appellants that the
Examiner has failed to show that a person of ordinary skill in the art would
have been motivated to combine the teachings of Wells with Malim,
Mangeat and Pincus to create the transgenic pig of the instant claims.
The arguments with respect to the combination of Wells, Malim,
Mangeate and Pincus are also applicable to claim 4.
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Application 12/622,886
Conclusion of Law
We find that the Examiner has not established by a preponderance of
the evidence that the rejected claims are obvious over Wells combined with
Malim, Mangeat, and Pincus as defined by 35 U.S.C § 103(a)
SUMMARY
We reverse the rejection of claims 1, 2, 4--9, and 11.
REVERSED
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