Ex Parte Palomba et al

Board of Patent Appeals and Interferences

May 12, 2009

10285874 (B.P.A.I. May. 12, 2009)

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.
10/285,874 10/31/2002 Maria Lia Palomba MSK.P-026-4 4321
52334 7590 05/13/2009
Larson & Anderson, LLC
re: MSK
P. O. BOX 4928
DILLON, CO 80435-4928
EXAMINER
BRISTOL, LYNN ANNE
ART UNIT PAPER NUMBER
1643
MAIL DATE DELIVERY MODE
05/13/2009 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 MARIA LIA PALOMBA,
ALAN HOUGHTON, JEDD WOLCHOK,
DAVID A. SCHEINBERG, and WENDY K. ROBERTS

__________

Appeal 2008-4403
Application 10/285,874
Technology Center 1600
__________

Decided:1 May 13, 2009
__________

Before DEMETRA J. MILLS, LORA M. GREEN, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
for stimulating an immune response, which the Examiner has rejected as
failing the enablement requirement and as obvious. We have jurisdiction
under 35 U.S.C. § 6(b). We reverse.

1 This case was heard in Oral Hearing on April 21, 2009.
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Statement of the Case
Background
“Differentiation antigens are tissue-specific antigens that are shared
by autologous and some allogeneic tumors of similar derivation, and on
normal tissue counterparts at the same stage of differentiation” (Spec. 1, ll.
22-25). According to the Specification, “[u]nfortunately, in most cases, the
immune system of the individual is tolerant of these antigens, and fails to
mount an effective immune response” (Spec. 2, ll. 14-15).
The Claims
Claims 1-3, 10-12, and 23-29 are on appeal2. We will focus on claim
1, which is representative and reads as follows:
1. A method for stimulating an immune response to a
tissue expressing CD20 in a subject individual of a first
species, comprising administering to the subject individual
an immunologically-effective amount of xenogeneic or
xenoexpressed CD20 antigen.

The Cited Art
Haupt et al., The Potential of DNA Vaccination against Tumor-
Associated Antigens for Antitumor Therapy, 227 EXP. BIOL. MED. 227-237
(2002).
Vincenzo Bronte, Genetic Vaccination for the Active Immunotherapy
of Cancer, 1 CURRENT GENE THERAPY 53-100 (2001).
You et al., Targeting Dendritic Cells to Enhance DNA Vaccine
Potency, 61 CANCER RESEARCH 3704-3711 (2001).
Nettelbeck et al., Gene Therapy, 16 TRENDS IN GENETICS 174-181
(2000).
Browne et al., Coupling and Uncoupling of Tumor Immunity and
Autoimmunity, 190 J. EXPERIMENTAL MEDICINE 1717-1722 (1999).

2 The Examiner withdrew claims 4-9, 13, and 14 based upon a
restriction requirement (App. Br. 1).
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H. Niemann, Transgenic farm animals get off the ground, 7
TRANSGENIC RESEARCH 73-75 (1998).
Mahato et al., Development of Targeted Delivery Systems for Nucleic
Acid Drugs, 4 J. of DRUG TARGETING 337-357 (1997).
Tedder et al., Cloning of a Complementary DNA Encoding a New
Mouse B Lymphocyte Differentiation Antigen, Homologous to the Human B1
(CD20) Antigen, and Localization of the Gene to Chromosome 19, 141 J.
IMMUNOLOGY 4388-4394 (1988).

The Issues
A. The Examiner rejected claims 1-3, 10-12 and 23-29 under 35 U.S.C.
§ 112, first paragraph as failing to comply with the enablement requirement
(Ans. 6-13).
B. The Examiner rejected claims 1-3, 10-12 and 23-29 under 35 U.S.C.
§ 103(a) as obvious over Bowne, You, Tedder, and Mahoto (Ans. 13).
A. 35 U.S.C. § 112, first paragraph Enablement Rejection
The Examiner finds that:
[T]he specification does not reasonably provide enablement
for overcoming tolerance to endogenous CD20 in any
subject by stimulating any immune response with any
xenogeneic CD20 antigen where the CD20 antigen is
encoded by DNA alone much less in a liposome
encapsulated DNA form or coated on a gold particle DNA
form or in any expression vector encoding the DNA where
the subject individual of a first species is any subject much
less a human and where the immune response is
immunoprotective against growth of any CD20-expressing
tumor.

(Ans. 6).
Appellants contend that the “Examiner has offered no reasons why a
person in the art would need undue experimentation to extend the teachings
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of the specification and the animal model results of vaccination against
CD20 to other vaccinations against CD20” (App. Br. 6).
In view of these conflicting positions, we frame the enablement issue
before us as follows:
Have Appellants demonstrated that the Examiner erred in concluding
that it would have required undue experimentation to stimulating an immune
response to a tissue expressing CD20 by administering a xenogeneic or
xenoexpressed CD20 antigen?
Findings of Fact (FF)
Breadth of the Claims
1. The Examiner finds that the “claims encompass using an
immunologically effective amount of any DNA encoding a xenogeneic
CD20 antigen or liposomes comprising DNA encoding the xenogeneic
CD20 antigen or gold particles coated with DNA encoding the xenogeneic
CD20 antigen” (Ans. 8).
Presence of Working Examples
2. The Specification teaches that “[m]ice immunized with the
human minigene (pNERIS-H8) displayed a slower pace of tumor take, as
shown in panel 3a and 3b. Long-term survival, defined as survival up to 60
days post-challenge, was modestly but statistically better in mice immunized
with pCR3-H8” (Spec. 7, ll. 1-4).
3. The Specification teaches that “T-cell responses against mouse
CD20 were observed following vaccination with human CD20 DNA” (Spec.
7, ll. 8-9).
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4. The Specification teaches that “[a]nalysis of the sera from mice
immunized with both human and mouse minigenes revealed the presence of
anti CD20 antibodies in about 80% of the animals tested” (Spec. 8, ll. 2-4).
Amount of Direction or Guidance Presented
5. The Specification teaches that the “[a]dministration of a
protein/peptide xenogeneic or xenoexpressed CD20 antigen can be
accomplished by several routes. First, the xenogeneic CD20 may be
administered as part of a vaccine composition” (Spec. 4, ll. 8-10).
6. The Specification teaches that “[x]enogeneic CD20 antigen
may also be introduced in accordance with the invention using a DNA
immunization technique” (Spec. 4, ll. 27-28).
7. The Specification teaches methods for routine cloning of the
CD20 sequence by reverse transcriptase PCR (see Spec. 9-10, Example 1).
8. The Specification teaches “preferred xenogeneic antigens will
be rodent antigens, for example mouse, but could come from other mammals
such as dog, cat, cow, or sheep, or from birds, fish, amphibian, reptile, insect
or other distantly related species” (Spec. 3, ll. 25-27).
State of the Art and Unpredictability of the Art
9. Haupt teaches that “DNA immunization, is known to induce
both antigen-specific cellular as well as humoral immune responses” (Haupt
228, col. 1).
10. Haupt teaches that “[r]ecently published studies have shown
that xenogeneic DNA immunization exploiting small differences in
expressed tumor antigen sequence can result in immune recognition of self-
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molecules in mice, whereas immunization with syngeneic DNA failed to do
so” (Haupt 231, col. 1-2).
11. Haupt teaches that “[a]nimals immunized with xenogeneic
human gp100 DNA were significantly protected from tumors after a
challenge with a syngeneic melanoma expressing gp100” (Haupt 231, col.
2).
12. Bronte teaches that “[i]mmunization with xenogeneic TAA was
shown to break tolerance, but their serendipitous isolation makes it difficult
to apply this strategy to the therapy of human tumors. What species will
supply the xenogeneic antigen? Should we use porcine, mouse, sheep or
monkey homologous antigen? It is clear that we cannot proceed empirically
in this search” (Bronte 84, col. 1-2).
13. Nettelbeck teaches that “[m]any laboratories have therefore
focused on the design of improved promoters for cancer gene therapy and
this review will give a brief account of the recently successful developments
in this research area” (Nettelbeck 175, col. 1).
Principles of Law
“In order to satisfy the enablement requirement of section 112, an
applicant must describe the manner of making and using the invention ‘in
such full, clear, concise, and exact terms as to enable any person skilled in
the art ... to make and use the same ....’ 35 U.S.C. § 112, para. 1.”
Rasmusson v. SmithKline Beecham Corp., 413 F.3d 1318, 1322 (Fed. Cir.
2005).
Factors to be considered in determining whether a
disclosure would require undue experimentation . . . include
(1) the quantity of experimentation necessary, (2) the
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amount of direction or guidance presented, (3) the presence
or absence of working examples, (4) the nature of the
invention, (5) the state of the prior art, (6) the relative skill
of those in the art, (7) the predictability or unpredictability
of the art, and (8) the breadth of the claims.

In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988).
The Examiner has the initial burden to establish a reasonable basis to
question the enablement provided for the claimed invention. See In re
Wright, 999 F.2d 1557, 1561-62 (Fed. Cir. 1993) (Examiner must provide a
reasonable explanation as to why the scope of protection provided by a
claim is not adequately enabled by the disclosure).
Analysis
The Specification provides substantial teachings regarding methods
for stimulating an immune response using a xenogeneic CD20 antigen,
including working examples of such a response in mouse model systems (FF
2-6). The Specification also teaches how to obtain CD20 antigens from
desired species by RT-PCR (FF 7).
The prior art cited by the Examiner, Haupt and Bronte, both teach that
DNA immunization stimulates an immune response and that the immune
response may protect against tumors (FF 8-12). Bronte does recognize some
unpredictability in selection of the xenogeneic antigen (FF 12). Nettelbeck
shows that promoters necessary for cancer gene therapy are taught by the
prior art (see FF 13).
Balancing the Wands factors, we agree with Appellants that undue
experimentation would not have been required to make and use the claimed
invention. To the extent that the Examiner argues the “how to make” prong,
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the Specification and prior art clearly teach how to obtain CD20 from any
desired xenogeneic species and also teach how to make plasmids with CD20
and promoters which will function to express that CD20 in the desired cell
types (FF 7, 8, 13). The Specification also teaches how to immunize using
the xenogeneic antigens after the CD20 containing plasmids are synthesized
(FF 2-6).
With regard to the “how to use” prong, the Specification and prior art
demonstrate that xenogeneic antigens clearly satisfy the claim requirement
to “stimulate an immune response” (see FF 2-5, 8-12). There is no doubt
that xenogeneic CD20 stimulated an immune response in mice (FF 2-5).
There is no reasonable reason to doubt that administration of xenogeneic
CD20 would stimulate an immune response in humans or any other desired
species, given the disclosures of the Specification and prior art (FF 2-5, 8-
12).
The entire discussion by the Examiner regarding “vaccination” is not
relevant to the instant claims, which do not use the word “vaccination”, and
do not even require prevention of a disease or disorder (see Ans. 18). See In
re Hiniker Co., 150 F.3d 1362, 1369 (Fed. Cir. 1998) (“the name of the
game is the claim”). The issue in claim 1 is whether administration of a
xenogeneic CD20 antigen will stimulate an immune response (see Claim 1).
The Examiner has not provided any evidence or reasoning to suggest that
this will not occur, and in fact, acknowledges that Appellants have elicited
such a response (see Ans. 20).
It may be that the Examiner intends this to be a scope of enablement
rejection, as nonenabling for humans, or in producing a prophylactic or
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therapeutic effect. If so, we are not persuaded by the scope of enablement
argument either, since there is specific evidence in the Specification that the
method has some therapeutic effect in a mouse model system and the
Examiner has provided no specific evidence that the method would not
function in humans or other species or using other plasmid constructs (FF 2-
13).
Moreover, the Examiner's apparent position that the Specification
cannot teach how to use the claimed method unless it teaches solutions to all
possible species and all possible plasmid vectors is contrary to controlling
case law. See, e.g., In re Brana, 51 F.3d 1560, 1568 (Fed. Cir. 1995).
In Brana, the claims were directed to compounds disclosed as anti-
cancer agents. Id. at 1562. The USPTO rejected the claims as nonenabled,
id. at 1563-64, despite working examples in Brana's specification showing
treatment of cancer in a mouse model. Id. at 1562-63. The USPTO argued
that the results of the mouse testing “are not reasonably predictive of the
success of the claimed compounds for treating cancer in humans.” Id. at
1567. The court concluded that this position “confuses the requirements
under the law for obtaining a patent with the requirements for obtaining
government approval to market a particular drug for human consumption.”
Id. The Brana court held that “[u]sefulness in patent law, and in particular
in the context of pharmaceutical inventions, necessarily includes the
expectation of further research and development. The stage at which an
invention in this field becomes useful is well before it is ready to be
administered to humans.” Id. at 1568.
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The facts in the instant case are better for Appellant than the facts in
Brana, since not only does the Specification show working examples, but
the cited art also shows evidence of success (FF 2-12).
Conclusions of Law
We conclude that Appellants have demonstrated that the Examiner
erred in finding that it would have required undue experimentation to
stimulating an immune response to a tissue expressing CD20 by
administering a xenogeneic or xenoexpressed CD20 antigen.

B. 35 U.S.C. § 103(a) over Bowne, You, Tedder, and Mahoto
The Examiner finds that:
It would have been prima facie obvious to one of
ordinary skill in the art at the time the invention was made to
substitute the human TRP/PCR3 vector in the method taught
by Bowne with an expression vector construct containing a
CD20 gene (i.e., a human CD 20 for injection into mice or
the mouse CD20 gene for injection into a xenogenic
recipient) of Tedder to yield a operable naked vector of You,
and to further encapsulate the expression vector with
liposomes of Mahato or to coat gold particles as taught by
Bowne, in order to provide an enhanced stimulation of an
active and specific immune response to a xenogeneic CD 20
antigen.

(Ans. 14-15).
Appellants contend that the “issue presented in this appeal is whether
the application is entitled to the benefit of the December 10, 1997 filing date
of PCT Application No. PCT/US97/22669. If the application is so entitled,
then the references cited are not prior art and the rejection must be reversed”
(App. Br. 9).
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In view of these conflicting positions, we frame the obviousness issue
before us as follows:
Have Appellants demonstrated that the Examiner erred in finding that
the disclosure in WO 98/25574 (PCT/US97/22669) does not reasonably
convey to one of ordinary skill in the art that Appellants possessed the
instantly claimed subject matter?
Findings of Fact
14. WO 98/25574 teaches that “[d]ifferentiation antigens are tissue-
specific antigens that are shared by autologous and some allogeneic tumors
of similar derivation” (WO 98/25574 1, ll. 4-5). WO 98/25574 teaches that
“differentiation antigens expressed by melanoma cells include Melan-
A/MART-1, Pmel17, tyrosinase, and gp75” (WO 98/25574 1, ll. 9-10).
15. WO 98/25574 teaches that “[d]ifferentiation antigens expressed
by lymphomas and leukemia include CD19 and CD20/CD20 B lymphocyte
differentiation markers” (WO 98/25574 1, ll. 10-12).
16. WO 98/25574 teaches that “[f]or treatment of cancers where the
tumor expresses differentiation antigens therefore, it would be desirable to
have a method for stimulating an immune response against the
differentiation antigen in vivo” (WO 98/25574 1, ll. 22-24).
17. WO 98/25574 teaches that “the therapeutic differentiation
antigen may be a differentiation antigen (wild-type or mutant) of the same
type from a species different from the individual being treated. For
example, a mouse differentiation antigen can be used to simulate an immune
response to the corresponding differentiation antigen in a human subject”
(WO 98/25574 2, ll. 13-16).
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18. WO 98/25574 teaches that “an immune response against a
target differentiation antigen can be stimulated by the administration of
xenogeneic differentiation antigen of the same type” (WO 98/25574 7, ll. 2-
4).
19. WO 98/25574 teaches that “administration of human gp75
broke the tolerance to gp75 in C57BL/6 mice” (WO 98/25574 11, ll. 4-5).
20. WO 98/25574 teaches that “[m]ice immunized with human
gp75+ SK-MEL-19 were also markedly protected against B16F10 melanoma
compared to unimmunized mice” (WO 98/25574 11, ll. 30-31).
21. Tedder teaches “the primary structure of the mouse homolog of
the human B1 [CD20] molecule deduced from a cloned cDNA” (Tedder
4388, col. 2).
Principles of Law
“In order to gain the benefit of the filing date of an earlier application
under 35 U.S.C. § 120, each application in the chain leading back to the
earlier application must comply with the written description requirement.”
Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997)
(citing In re Hogan, 559 F.2d 595, 609 (CCPA 1977)). In order to satisfy
the written description requirement, “the applicant must … convey with
reasonable clarity to those skilled in the art that, as of the filing date sought,
he or she was in possession of the invention.” Vas-Cath Inc. v. Mahurkar,
935 F.2d 1555, 1563-64 (Fed. Cir. 1991). Thus, “[t]he possession test
requires assessment from the viewpoint of one of skill in the art.” Moba,
B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1320 (Fed. Cir. 2003).
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Analysis
WO 98/25574 broadly discusses the use of any differentiation antigen,
and only lists six different differentiation antigens, including CD20 (FF 14-
15). WO 98/25574 directly teaches stimulation of immune response against
differentiation antigens (FF 16). WO 98/25574 also directly teaches a
preference for the use of xenogeneic antigens to stimulate the immune
response (FF 17-18). Finally, WO 98/25574 teaches that gp75, another of
the six differentiation antigens listed, functions to stimulate immune
response, break tolerance and provide a protective immune response (FF 19-
20).
We agree with Appellants that the disclosure of WO 98/25574, from
which the instant application depends, reasonably conveys to the skilled
artisan that Appellants were in possession, and enabled for, a method of
stimulation of immune responses with xenogeneic differentiation antigens,
including CD20 (FF 14-20).
We are not persuaded by the Examiner’s argument that WO 98/25574
does not teach “antigenic epitopes of human or murine CD20, embodiments
for CD20 proteins/peptide and DNA vectors encoding the CD20
proteins/peptides” (Ans. 24). Claims 1-3, 10-12 and 23-29 do not include
any requirement for “antigenic epitopes” and the ordinary artisan using
CD20 to stimulate an immune response would have followed the guidance
of WO 98/25574 to utilize the whole protein, not particular regions (FF 14-
20).
Further, Tedder discloses that the mouse CD20 gene was cloned using
standard techniques, and the Examiner has provided no reason to expect
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unpredictability in cloning CD20 genes from other species or in moving
these cloned genes into DNA vectors as disclosed in WO 98/25574 (FF 21).
Since we find that Appellants are entitled to the filing date of WO
98/25574 of December 10, 1997, we find that Bowne and You are not prior
art to claims 1-3, 10-12, and 23-29 and the obviousness rejection necessarily
is reversed.
Conclusion of Law
We find that Appellants have demonstrated that the Examiner erred in
finding that the disclosure in WO 98/25574 (PCT/US97/22669) does not
reasonably convey to one of ordinary skill in the art that Appellants
possessed the instantly claimed subject matter.
SUMMARY
In summary, we reverse the rejection of claims 1-3, 10-12, and 23-29
under 35 U.S.C. § 112, first paragraph enablement.
We reverse the rejection of claims 1-3, 10-12, and 23-29 under 35
U.S.C. § 103(a) over Bowne, You, Tedder, and Mahoto.
REVERSED
lp

LARSON & ANDERSON, LLC
RE: MSK
P. O. BOX 4928
DILLON CO 80435-4928