Ex Parte High

Board of Patent Appeals and Interferences

Sep 3, 2010

11065117 (B.P.A.I. Sep. 3, 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.
11/065,117 02/23/2005 Katherine A. High 0800-0024.01 9975
31048 7590 09/07/2010
ROBINS & PASTERNAK LLP
1731 EMBARCADERO ROAD
SUITE 230
PALO ALTO, CA 94303
EXAMINER
WHITEMAN, BRIAN A
ART UNIT PAPER NUMBER
1635
MAIL DATE DELIVERY MODE
09/07/2010 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 KATHERINE A. HIGH
__________

Appeal 2010-003211
Application 11/065,117
Technology Center 1600
__________

Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and
STEPHEN WALSH, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL1
This is an appeal under 35 U.S.C. § 134 involving claims to a method
for treating hemophilia. The Examiner rejected the claims as obvious. We
have jurisdiction under 35 U.S.C. § 6(b). We affirm.

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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Statement of the Case
The Claims
Claims 13, 14, 16-20, and 27 are on appeal. The claims have
not been argued separately and therefore stand or fall together. 37
C.F.R. § 41.37(c)(1)(vii). Claim 13 is representative and reads as
follows:
13. A method of treating hemophilia in a
human, comprising:
(a) providing at least one recombinant
adeno-associated virus (rAAV) virion, said rAAV
virion comprising a vector further comprising a
heterologous nucleic acid sequence further
comprising a gene encoding Factor IX; and
(b) delivering said rAAV virions to the liver
of said human by retrograde delivery of said rAAV
virions into the bile duct and under conditions
wherein said gene is expressed at a therapeutic
level, wherein said human has preexisting anti-
AAV antibodies.

The issue
The Examiner rejected claims 13, 14, 16-20, and 27 under 35 U.S.C. §
103(a) as obvious over Snyder,2 Couto,3 and Yang4 (Ans. 3-5).
The Examiner finds that the ordinary artisan “would have been
motivated to administer AAV to the bile duct system using retrograde
administration because Yang teaches that this route of administration results

2 Snyder et al., US 2002/0151509 A1, Oct. 17, 2002.
3 Couto et al., US 6,200,560 B1, Mar. 13, 2001.
4 Yang et al, An approach for treating the hepatobiliary disease of
cystic fibrosis by somatic gene transfer, 90 PROC. NATL. ACAD.
SCI. USA 4601-4605 (1993).
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in heterologous gene expression in virtually all cells of the intra-hepatic duct
in vivo” (Ans. 4 ).
Appellants contend that “[a]bsent the teaching provided in Appellant's
specification, there is simply no suggestion in Snyder or Couto regarding
retrograde administration and hence no recognition that retrograde
administration of rAAV via the ductal system is useful in avoiding pre-
existing antibody responses to AAV.” (App. Br. 7.) Appellants contend that
if “the Examiner is relying on retrograde delivery as having the inherent
property of avoiding an immune response, Appellant submits a retrospective
view of inherency is not a substitute for some teaching or suggestion to
arrive at the claimed invention” (id. at 8).
Appellants contend that “Snyder actually teaches away from the
combination suggested by the Office” (id. at 9). Appellants contend that
“Snyder recognizes that inhibition or blockage of transduction by
immunosuppression of the rAAV viral vectors may be a problem. However,
Snyder does not teach or suggest that the method of administration should be
altered. Rather, Snyder provides a solution in the form of
immunosuppressant therapy” (id.).
The issue with respect to this rejection is: Does the evidence of record
support the Examiner’s conclusion that claim 13 is obvious over Snyder,
Couto, and Yang?
Findings of Fact
1. Snyder teaches that “recombinant AAV vectors may be used to
deliver exogenous or endogenous polynucleotides to the cells of the liver of
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an intact mammal for effective expression of a gene of interest” (Snyder 3 ¶
0035).
2. Snyder teaches that a potential disease target is hemophilia B
and the factor IX gene for its therapy (see Snyder 6 ¶ 0090).
3. Snyder teaches that to “deliver the vector specifically to a
particular region of the liver, it may be administered by intraportal injection .
. . In certain embodiments, the vector will be administered via an
intravascular approach” (Snyder 7 ¶¶ 0105-0106).
4. Couto teaches “AAV vectors suitable for hemophilia gene
therapy. More particularly, these AAV vectors are suitable for delivering
nucleic acids encoding Factor VIII into a recipient subject” (Couto, col. 1, ll.
13-17).
5. Couto teaches that although “85% of the human population is
seropositive for AAV-2, the virus has never been associated with disease in
humans” (Couto, col. 12, ll. 39-41).
6. Couto teaches that the AAV compositions “can be delivered
subcutaneously, epidermally, intradermally, intrathecally, intraorbitally,
intramucosally (e.g., nasally, rectally and vaginally), intraperitoneally,
intravenously, intraarterially, orally, or intramuscularly. Other modes of
administration include oral and pulmonary administration, suppositories, and
transdermal applications. In particularly preferred embodiments, the
compositions are administered intravenously in the portal vasculature or
hepatic artery” (Couto, col. 19, ll. 9-17).
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7. Yang teaches “a strategy for preventing the development of CF
liver disease that is based on the reconstitution of CFTR gene expression in
the biliary tract by somatic gene transfer” (Yang 4601, col. 2).
8. Yang teaches that “[s]pecifically targeting genes to the
relatively quiescent epithelial cells of the biliary tract requires new
strategies. We have used recombinant adenovirus because of their ability to
transfect genes in nondividing cells” (Yang 4602, col. 2).
9. Yang teaches that the “recombinant genes are specifically
targeted to biliary epithelial cells by retrograde infusion of adenovirus into
the biliary tract via the common bile duct” (Yang 4602, col. 2).
10. Yang teaches that the:
[S]trategy for targeting genes to biliary epithelia described
in this report has several features that make it attractive for
application to humans. First, it should be feasible to deliver
recombinant viruses to the human biliary tract by a
nonsurgical approach, endoscopic retrograde
cholangiography . . . Another advantage of this approach is
the specificity of gene transfer achieved by virtue of the
anatomical constraints of the compartment into which the
virus is delivered; the primary target of gene transfer is the
biliary epithelial cells, with recombinant gene expression
detected in a minority of hepatocytes. Finally, excess virus is
delivered immediately into the duodenum and excreted in
the stool.

(Yang 4603, col. 2 to 4604, col. 1.)
Principles of Law
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). “If a person of
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ordinary skill can implement a predictable variation, § 103 likely bars its
patentability.” Id. at 417. Moreover, an “[e]xpress suggestion to substitute
one equivalent for another need not be present to render such substitution
obvious.” In re Fout, 675 F.2d 297, 301 (CCPA 1982). As noted by the
Court in KSR, “[a] person of ordinary skill is also a person of ordinary
creativity, not an automaton.” 550 U.S. at 421.
A reference may be said to teach away when a person of
ordinary skill, upon reading the reference, would be
discouraged from following the path set out in the reference,
or would be led in a direction divergent from the path that
was taken by the applicant. The degree of teaching away
will of course depend on the particular facts; in general, a
reference will teach away if it suggests that the line of
development flowing from the reference’s disclosure is
unlikely to be productive of the result sought by the
applicant.
In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994).
Analysis
Snyder teaches treatment of hemophilia in humans by delivering
adeno-associated virus vectors with a heterologous nucleic acid sequence
expressing the Factor IX gene by several delivery routes (FF 1-3). Couto
also teaches treatment of hemophilia in humans by delivering an adeno-
associated virus vector with a heterologous gene sequence using a wide
variety of delivery routes (FF 4, 6). Couto also teaches that 85% of humans
have preexisting anti-AAV antibodies (FF 5).
Yang teaches a route of administration of a virus vector and Yang
teaches advantages of this delivery mode, specifically that the:
[S]trategy for targeting genes to biliary epithelia described
in this report has several features that make it attractive for
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application to humans. First, it should be feasible to deliver
recombinant viruses to the human biliary tract by a
nonsurgical approach, endoscopic retrograde
cholangiography . . . Another advantage of this approach is
the specificity of gene transfer achieved by virtue of the
anatomical constraints of the compartment into which the
virus is delivered; the primary target of gene transfer is the
biliary epithelial cells, with recombinant gene expression
detected in a minority of hepatocytes. Finally, excess virus is
delivered immediately into the duodenum and excreted in
the stool.

(Yang 4603, col. 2 to 4604, col. 1; FF 10.)
Applying the KSR standard of obviousness to the findings of fact, we
conclude that the person of ordinary creativity would have predictably
treated patients with the AAV vectors of Snyder and Couto via the route of
administration of Yang since Yang teaches a variety of advantages of this
approach (FF 10). Such a combination is merely a “predictable use of prior
art elements according to their established functions.” KSR, 550 U.S. at 417.
Appellants contend that “[s]ubstituting Yang’s delivery technique for
Snyder’s would result in delivery of the virions to the liver, not to the
gallbladder and duodenum and hence expression would not occur in the
gallbladder and duodenum” (App. Br. 7).
We are not persuaded of error. Yang expressly teaches that
expression occurs in the biliary tract (FF 7-9). The ordinary artisan, in
delivering the Snyder virus by Yang’s method, would reasonably follow
Yang’s method and achieve Yang’s results in order to obtain the benefits
disclosed by Yang (FF 10).
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Appellants contend that “[a]bsent the teaching provided in Appellant's
specification, there is simply no suggestion in Snyder or Couto regarding
retrograde administration and hence no recognition that retrograde
administration of rAAV via the ductal system is useful in avoiding pre-
existing antibody responses to AAV.” (App. Br. 7.) Appellants contend that
if “the Examiner is relying on retrograde delivery as having the inherent
property of avoiding an immune response, Appellant submits a retrospective
view of inherency is not a substitute for some teaching or suggestion to
arrive at the claimed invention” (id. at 8).
We are not persuaded. That the prior art has a different reason or
motivation to apply the approach of Yang is of no moment as long as there is
a reason, suggestion, or motivation to make the combination. See In re
Kemps, 97 F.3d 1427, 1430 (Fed. Cir, 1996)(“[T]he motivation in the prior
art to combine the references does not have to be identical to that of the
applicant to establish obviousness.”). We agree with the Examiner that a
reason to deliver the AAV vectors of Snyder and Couto by the method of
Yang is “because Yang teaches that this route of administration results in
heterologous gene expression in virtually all cells of the intra-hepatic duct in
vivo” (Ans. 4).
Appellants contend that “Snyder actually teaches away from the
combination suggested by the Office” (App. Br. 9). Appellants contend that
“Snyder recognizes that inhibition or blockage of transduction by
immunosuppression of the rAAV viral vectors may be a problem. However,
Snyder does not teach or suggest that the method of administration should be
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Application 11/065,117

9
altered. Rather, Snyder provides a solution in the form of
immunosuppressant therapy” (App. Br. 9).
We are not persuaded. When Snyder teaches that immunosuppressive
methods may be recommended, Snyder is teaching this in the context of
multiple administrations which may raise immune response (see Snyder 10
¶ 0143). Snyder does not teach that alternate modes of delivery should not
be used, or that these alternate modes will result in greater or lesser immune
response issues, and has no teaching that retrograde delivery into the bile
duct as taught by Yang would be undesirable in any way. Like our appellate
reviewing court, “[w]e will not read into a reference a teaching away from a
process where no such language exists.” DyStar Textilfarben GmbH v. C.H.
Patrick Co., 464 F.3d 1356, 1364 (Fed. Cir. 2006).
Appellants also argue that “one of ordinary skill in the art would not
have a reasonable expectation of success in substituting AAV for the
adenovirus used in the Yang methods” (App. Br. 11).
We are not persuaded. Appellants rely on Wilson5 (see App. Br. 11),
who does not teach that AAV will not work, but simply does not mention
AAV as a viral delivery system (see, e.g., Wilson 2 ¶ 0026)(“[V]arious
viruses that are capable of infecting epithelial cells can be recombinantly
manipulated to carry the gene of interest without affecting their infectivity”).
Given the express teachings of AAV as a virus vector for hemophilia
in Snyder and Couto and the successful delivery system of Yang, we
conclude that the prior art provided a reasonable expectation of success (see
FF 1-10). Kubin stated that “[r]esponding to concerns about uncertainty in

5 Wilson, US 2005/0048043 A1, Mar. 3, 2005.
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the prior art influencing the purported success of the claimed combination,
this court [in O’Farrell] stated: ‘[o]bviousness does not require absolute
predictability of success … all that is required is a reasonable expectation of
success.”’ In re Kubin, 561 F.3d 1351, 1360 (Fed. Cir. 2009) (citing In re
O’Farrell, 853 F.2d 894, 903-904 (Fed. Cir. 1988)).
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that claim
13 is obvious over Snyder, Couto, and Yang.
SUMMARY
In summary, we affirm the rejection of claim 13 under 35 U.S.C. §
103(a) as obvious over Snyder, Couto, and Yang. Pursuant to 37 C.F.R. §
41.37(c)(1)(vii)(2006), we also affirm the rejection of claims 14, 16-20, and
27 as these claims were not argued separately.

No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1)(iv)(2006).

AFFIRMED

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ROBINS & PASTERNAK LLP
1731 EMBARCADERO ROAD
SUITE 230
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