Ex Parte Weinstein et al

Patent Trial and Appeal Board

Aug 2, 2016

10566586 (P.T.A.B. Aug. 2, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
10/566,586 08/23/2007
40334 7590
Jordan IP Law, LLC
12501 Prosperity Drive
Suite 401
Silver Spring, MD 20904
08/04/2016
FIRST NAMED INVENTOR
Raymond Weinstein
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.
6000-2001 7191
EXAMINER
PARKIN, JEFFREYS
ART UNIT PAPER NUMBER
1648
NOTIFICATION DATE DELIVERY MODE
08/04/2016 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):
info@jordaniplaw.com
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte RAYMOND WEINSTEIN,
MICHAEL WEINSTEIN, and KEN ALIBEK
Appeal2014-005944
Application 10/566,586
Technology Center 1600
Before JEFFREY N. FREDMAN, ULRIKE W. JENKS, and
RICHARD J. SMITH, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal1under35 U.S.C. § 134 involving claims to a method
of diminishing HIV replication. The Examiner rejected the claims as failing
to comply with the enablement requirement. We have jurisdiction under
35 U.S.C. § 6(b). We affirm.
1 Appellants identify the Real Parties in Interest as the inventors,
Raymond Weinstein, Michael Weinstein, and Kenneth Alibek (see
App. Br. 3).
Appeal2014-005944
Application 10/566,586
Statement of the Case
Background
"AIDS is caused by a virus known as human immunodeficiency virus
('HIV') which presently includes HIV-1 and HIV-2" (Spec. 1: 11-13). The
Specification teaches that a "poxvirus or a component thereof, can be used to
treat and/or prevent infection caused by any virus, preferably a lentivirus,
such as HIV, that uses a CCR5 chemokine receptor for its infection of cells"
(Spec. 2:13-15).
The Claims
Claims 1, 7-13, 24, and 56-61 are on appeal. Independent claim 1 is
representative and reads as follows:
1. A method of diminishing HIV replication comprising:
identifying a subject exposed to HIV or at risk of
exposure to HIV; and
administering a replication-competent vaccinia virus
in response to identif;ing said subject and in an effective
amount at least to diminish the replication at least of CCR5-
tropic HIV in said subject.
The Issue
The Examiner rejected claims 1, 7-13, 24, and 56-61under35 U.S.C.
§ 112, first paragraph, enablement (Ans. 2-5).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner's conclusion that the Specification does not
enable the claimed invention?
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Findings of Fact
Breadth of Claims
1. The Examiner finds that the "claims are broadly directed
toward any 'vaccinia' virus. The claims do not require the administration of
replication-impaired or attenuated vaccine forms. It has been well-
documented that replication-competent vaccinia virus can cause
complications in immunocompromised patients (e.g., HIV-I-infected
patients). The claims are NOT limited to any particular vaccinia virus
strain"
(Ans. 4).
Presence of Working Examples
2. The Specification teaches a single, in vitro example where
PBMCs (peripheral blood mononuclear cells) from ten subjects immunized
with vaccinia within the previous 3 to 6 months, and ten subjects never been
immunized with vaccinia were incubated with CCR5 and CXCR4 tropic
strains of HIV and viral replication measured by RT assays (Spec. 17: 8 to
19:6).
3. The Specification teaches that
there is a statistically significant difference between the
vaccinated and non-vaccinated subjects in culture series Band
C [using CCR5 tropic HIV] (p=.035 and .013 respectively) that
increases by day 13 (p=.017 and .008 respectively), indicating a
resistance to infection by HIV in the vaccinated subjects ...
while infection was easily achieved with the T-cell (CXCR4)
tropic HIV in cultures D, E and F, indicate these finding were
not the result of laboratory error.
(Spec. 19:9-17).
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Application 10/566,586
Amount of Direction or Guidance Presented
4. The Specification teaches that:
Any strain of vaccinia virus, or components thereof, can be
utilized to achieve a prophylactic and/or therapeutic effect,
including, but not limited to, e.g., strains available from the
ATCC, ECACC, or other virus collections, replication-
competent, replication-deficient, non-replicating, attenuated
strains, modified vaccinia Ankara (MVA), vaccinia virus
Ankara, NYV AC (ATCC No. VR-2559) replication-deficient
vaccinia viruses, VV Copenhagen, VV W estem Reserve, VV
Wyeth (ATCC No. VR325), Elstree, strains deficient in vCCI
(Reading et al., J. Immunol., 170: 1435-42, 2003), and/or vGF,
strains comprising one or more copies of the 1 7K
myristyloprotein, poxvirus strains, CCRS-dependent poxvirus
strains, etc.
(Spec. 4: 1-9).
5. The Specification teaches that "[a]ny subject can be
administered a poxvirus in accordance with the present invention, including
subjects who have been exposed to HIV, but have not yet developed HIV
infection, as well as subjects who have progressed to one or more of the
clinical symptoms of HIV infection" (Spec. 6: 14-17).
6. The Specification teaches that "[ v ]accination with vaccinia can
be associated with adverse reactions. Those at highest risk include, e.g.,
pregnant women, immunocompromised patients (e.g. HIV-positive)" (Spec.
8:20-22).
7. The Specification teaches that
a dose of the poxvirus, or component thereof, is the amount of
virus which is useful for accomplishing the therapeutic or
prophylactic effect ... smallpox immunization is usually
achieved by a single vaccination with a booster every 5-10
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Application 10/566,586
years. To maintain protection against HIV, more frequent
vaccination can be used, e.g., multiple times a year, at least
twice a year, yearly, every two years, every three years, more
than once every less than five years, more than once every less
than ten years, etc.
(Spec. 9:6-14).
State of the Prior Art and Unpredictability of the Art
8. Vanpouille2 teaches that "V ACV [vaccinia virus] preferentially
depletes activated T cells of the CCR5+ CD4+ phenotype, thus dramatically
suppressing replication of the R5 strain of HIV-1" (Vanpouille 1245 8, col.
2).
9. Vanpouille teaches that "[i]nactivated VACV and MVA did not
suppress R5sf-162 replication, indicating that VA CV-induced inhibition of
HIV-1 required VACV replication" (Vanpouille 12462, col. 1).
10. Vanpouille teaches that "[a ]s the CCR5+ T cells are
preferentially depleted at the same time, replication of RS-tropic HIV-1 is
particularly suppressed in tissues coinfected by VACV and HIV-1."
(Vanpouille 12463, col. 2).
11. Vaccari3 teaches that "experimental depletion of CD4 + T cells
at the time of infection decreases the durability of humoral and T-cell
response" (Vaccari 498, col. 1 ).
2 Vanpouille et al., Interactions between Human Immunodeficiency
Virus Type 1 and Vaccinia Virus in Human Lymphoid Tissue Ex
Vivo, 81J.Virology12458-64 (2007) ("Vanpouille").
3 Vaccari et al., CD4+ T-cell loss and delayed expression of
modulators of immune responses at mucosa! sites of vaccinated
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12. Vaccari teaches that:
Here we have evaluated the ability of vaccination with a DNA
prime-MY A boost regimen to protect mucosal site from CD4+
T-cell loss and analyzed not only mononuclear cell suspension
from minced tissues, but also in intact tissues by immune
histochemistry. We found that CD4+ T cells were not spared in
the vaccinated group despite the ability of this vaccine regimen
to induce mucosal immune responses
(Vaccari 504, col. 1 ).
13. Weinstein, 4 essentially a published form of the instant
Specification, teaches "reduced CCR5-tropic HIV-1 replication in PBMC
cultures from vaccinia immunized subjects vaccinated up to 14 months prior
to their study. A statistically significant reduction in replication did not
occur in cultures infected with a CXCR4-tropic HIV-1, although there was a
trend toward reduced replication" (Weinstein 4, col. 2).
14. Singh5 teaches that "[d]ual-tropic [HIV] strains infect all three
target cells, and dual-tropic prototypes use both CCR5 and CXCR4 (R5X4
variants)" (Singh 957, col. 1 ).
macaques following SIVmac2s1 infection, 1 Mucosal Immunology
497-507 (2008) ("Vaccari").
4 Weinstein et al., Significantly reduced CCR5-tropic HIV-I
replication in vitro in cells from subjects previously immunized
with Vaccinia Virus, 11 BMC Immunology 1-6 (2010)
("Weinstein").
5 Singh et al., Concordant Utilization of Macrophage Entry
Coreceptors by Related Variants within an HIV Type 1
Primary Isolate Viral Swarm, 1 7 AIDS Res. Human Retroviruses
957-63 (2001) ("Singh").
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15. Michler6 teaches that "[ v ]iral tropism (i.e., macrophage or T
cell tropism) is largely linked to coreceptor usage, with CXCR4(X4)-
utilizing viruses being T-tropic and syncytium-inducing (SI), and CCRS
(R5) utilizing viruses being M-tropic and non-syncytium-inducing (NSI)"
(Michler 743, col. 2).
16. Stevenson7 teaches that"[ d]espite considerable advances in
HIV science in the past 20 years, the reason why HIV-1 infection is
pathogenic is still debated and the goal of eradicating HIV-1 infection
remains elusive" (Stevenson, abstract).
17. Gallo8 teaches that:
There is no doubt that successful development of an HIV-
preventive vaccine does present some unusual obstacles.
A second obstacle to an HIV-preventive vaccine is that
we have no truly useful small animal model for studying HIV
infection ....
A third apparent problem is that we do not know with
certainty which immune response will provide protection ....
A fourth difficulty is HIV strain variation ....
The fifth, and in my view the most important obstacle, is
that HIV as a retrovirus integrates its genes into the target cell
6 Michler et al., Genotypic Characterization and Comparison of
Full-Length Envelope Glycoproteins from South African
HIV Type 1 Subtype C Primary Isolates That Utilize CCR5 and/or
CXCR4, 24 AIDS Res. Human Retroviruses 743-51 (2008)
("Michler").
7 Stevenson, M., HIV-I Pathogenesis, 9 Nature Medicine 853-60
(2003).
8 Gallo, R., The end or the beginning of the drive to an HIV-
preventive vaccine: a view from over 20 years, 366 Lancet 1894-
98 (2005).
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DNA, thereby quickly establishing a lifelong infection if not
stopped at the time of initial exposure.
(Gallo 1894, col. 1 to 2).
18. McMichael9 teaches that "[t]here is therefore a desperate need
for a [HIV] vaccine. Yet despite increasingly intense efforts, development
of a vaccine is still a long way off' (McMichael 228, col. 1 ).
19. Connick10 teaches that "despite evidence that HIV- I-specific
CTL are abundant and capable of cytolytic function, they are unable to fully
suppress viral replication in vivo resulting in the progressive depletion of
CD4+ T cells and, ultimately, death in untreated individuals" (Connick 6975,
col. 2).
20. Suzuki 11 teaches that "[ m ]easurement of the enzyme reverse
transcriptase (RT) using the RT assay is the most widely used procedure for
detection and quantitation of human immunodeficiency virus (HIV) in
studies to identify compounds with activity against HIV and for detecting
HIV in human peripheral blood mononuclear cells (PBMC)" (Suzuki 21 ).
21. Clapham12 teaches that "CCR5 and CXCR4 are the major co-
receptors and all HIV-I isolates can use one or both ... CCR5, however, is
9 McMichael, A., HIV Vaccines, 24 Ann. Rev. Immunol. 227-55
(2006).
10 Connick et al., CTL Fail to Accumulate at Sites of HIV-I
Replication in Lymphoid Tissue, 178 J. Immunology 6975-83
(2007) ("Connick").
11 Suzuki et al., Colorimetric reverse transcriptase assay for HIV-
I, 41 J. Virological Methods 21-28 (1993) ("Suzuki").
12 Clapham and McKnight, HIV-I receptors and cell tropism, 58
British Medical Bulletin 43-59 (2001) ("Clapham").
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not the only transmission route and a few HIV+ ~32 CCR5 homozygotes
have been identified. These individuals (where tested) appear to carry
CXCR4-using viruses" (Clapham 45).
22. Brichacek13 teaches that "[ s ]ince CCR5 is a co-receptor for the
majority of transmitted HIV-1 strains, the observed cytokine profile could
provide resistance to HIV-1 infection through interference with virus
interaction with CCR5" (Brichacek 2, col. 2).
23. Wharton14 teaches that "smallpox vaccination is
contraindicated for persons ... who have conditions associated with
immunosuppression" (Wharton 2).
24. Wharton teaches that "[s ]mallpox vaccine should not be
administered to persons with human immunodeficiency virus infection (HIV)
or acquired immunodeficiency syndrome (AIDS) as part of a pre-event
program because of their increased risk for progressive vaccinia"
(Wharton 3).
13 Brichacek et al., Long-term changes of serum chemokine levels
in vaccinated military personnel, 7 BMC Immunology 1-6 (2006)
("Brichacek").
14 Wharton et al., Recommendations for Using Smallpox Vaccine in
a Pre-Event Vaccination Program, 52 MMWR 1-16 (2003) (We
follow the page numbering where pages are numbered 1-23 in
Examiner's cited copy) ("Wharton").
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Application 10/566,586
25. Amoroso15 teaches that
large randomized clinical trials comparing the combination of
TDF and NVP with the more widely studied combination of
TDF and EFV have not been performed. There are no obvious
reasons why the combination of TDF and NVP should not be
highly active, and several prospective clinical trials have shown
efficacy. Yet 2 small studies comprising less than 42 patients
did suggest that the combination of TDF + NVP and
emtricitabine or lamivudine (XTC) has higher virologic failure
rates than anticipated.
(Amoroso 314, col. 2; references omitted).
Principles of Law
When rejecting a claim under the enablement
requirement of section 112, the PTO bears an initial burden
of setting forth a reasonable explanation as to why it
believes that the scope of protection provided by that claim
is not adequately enabled by the description of the invention
provided in the specification of the application.
In re Wright, 999 F.2d 1557, 1561-62 (Fed. Cir. 1993). "[T]he question of
undue experimentation is a matter of degree. The fact that some
experimentation is necessary does not preclude enablement; what is required
is that the amount of experimentation 'must not be unduly extensive."' PPG
Indus., Inc. v. Guardian Indus. Corp., 75 F.3d 1558, 1564 (Fed. Cir. 1996).
Factors to be considered in determining whether a
disclosure would require undue experimentation ... include
(1) the quantity of experimentation necessary, (2) the
15 Amoroso et al., Treatment Outcomes of Recommended First-
Line Antiretroviral Regimens in Resource-Limited Clinics, 60 J.
Acquired Immune Deficiency Syndrome 314-20 (2012)
("Amoroso").
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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).
Analysis
In addressing the Wands factors, the Examiner has provided
substantial evidence of unpredictability that relates to five different
dimensions of claim scope: (i) the scope of claim 1 encompasses in vivo
and in vitro effects in any human cell type, but the evidence of record is
drawn solely to in vitro efficacy data in PBMCs (FF 3); (ii) the scope of
claim 1 encompasses subjects exposed to HIV, subjects that the
Specification indicates encompasses symptomatic patients with the acquired
immune deficiency syndrome (AIDS) (FF 5) but the evidence shows that
vaccinia virus cannot be safely given to immunocompromised individuals
including AIDS patients (FF 6, 23, 24); (iii) the scope of claim 1
encompasses a single vaccination for any period of time prior to efficacy in
diminishing HIV replication (FF 7), with some teaching that protection lasts
10 years (FF 7), but the working examples solely show in vitro efficacy in
cells from patients immunized within 3 to 6 months of testing (FF 2); (iv)
the scope of claim 1 encompasses diminishing replication of HIV viruses of
any tropism, but the prior art suggests that HIV may be dual tropic to
CXCR4 and the working example is limited to CCR5 tropism (FF 8-15);
and (v) the scope of claim 1 is drawn to prevention using any replication
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competent vaccinia virus whatsoever (FF 1 ), but the working example is
limited to a single strain of vaccinia virus (FF 3).
In addition to these issues with claim scope, the Examiner has cited
several references that demonstrate severe unpredictability in developing
HIV vaccines, with Gallo identifying five unsolved obstacles to an HIV
vaccine (FF 1 7), and Stevenson, McMichael, and Connick evidencing the
unpredictability of HIV vaccines (FF 16, 18, 19).
There is only a single working example, limited to an in vitro analysis,
using cells from individuals not exposed to HIV, who were immunized 3 to
6 months prior to testing and that example only shows protection for CCR5
tropic HIV, not CXCR4 tropic HIV (FF 2). Claim 1 states diminishing
replication "at least of CCR5-tropic HIV." The use of "at least," a phrase
not limiting to the specific CCR5-tropic HIV, reasonably suggests that claim
1 may be interpreted as encompassing treatment of other tropisms.
There is generic guidance in the Specification listing multiple vaccinia
virus strains (FF 4), multiple possible patient subjects (FF 5) and multiple
vaccination schedules (FF 7), but the Specification provides no specific
guidance on which virus strains, which subjects, and which vaccination
schedules will actually result in diminishing the replication of any HIV, even
CCR5 tropic HIV.
The prior art, in addition to establishing unpredictability as already
noted (FF 16, 18, 19), also teaches that vaccinia virus inhibits HIV by
depleting (i.e., killing) CCR5+ CD4 cells (FF 8-10). However, neither the
cited prior art nor the Specification provide any guidance on the duration of
this effect. While the prior art recognizes that measuring HIV replication by
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measuring reverse transcriptase activity is routine (FF 20), this teaching does
not address the identified scope of enablement issues nor the demonstrated
unpredictability of HIV vaccines discussed above.
Therefore, even with a high level of skill in the art, the remaining
Wands factors support the Examiner's conclusion that
In order to practice the claimed invention the skilled artisan
would need a rational understanding of the therapeutic or
protective correlates. This would enable the skilled artisan to
assess relevant study parameters (e.g., vaccinia strain to be
utilized, immunization regimen, etc.) and ascertain if the
invention would work. Simply measuring RT levels does not
address these concerns.
(Ans. 6). We therefore agree with the Examiner that balancing all of these
factors supports a finding of undue experimentation (see Ans. 5). See In re
Fisher, 427 F.2d 833, 839 (CCPA 1970) ("[T]he scope of the claims must
bear a reasonable correlation to the scope of enablement provided by the
specification to persons of ordinary skill in the art.").
Decisions by the Federal Circuit support this conclusion of undue
experimentation. In Alza, the specific compound, methylphenidate, used for
treating ADHD was known and the "enablement issue reduce[ d] to factual
considerations with regard to whether undue experimentation is required to
make oral dosage forms other than osmotic dosage forms that meet the
limitations of the claims." Alza Corp. v. Andrx Pharms., LLC. 603 F.3d 935,
938 (Fed. Cir. 2010). In that much simpler situation, where the compound
was known to be effective and alternative dosage forms were known to exist,
Alza found that the "Wands factors weigh in favor of finding that the
experimentation required to practice part of the claimed invention was not
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routine." Id. at 943-944. Here, where there are a variety of different
replication competent vaccinia viruses that may be used, a variety of
different patients in different immunocompromised states, a variety of
different immunization regimens, different HIV tropisms, both in vivo and
in vitro analyses, and substantial evidence of unpredictability, the Wands
factors also weigh in favor of a finding that the experimentation necessary to
enable claim 1 was not routine.
Appellants contend that "[i]t would have been routine for one of
ordinary skill in the art to draw blood samples from a cohort, process the
blood samples to separate cells, isolate and culture the cells, introduce a
virus strain to the culture, and measure viral replication according to known
methods" (App. Br. 10).
We find this argument unpersuasive because the claim is not limited
to routine measurements of replication of an HIV in culture, but
encompasses in vivo therapeutic treatment of HIV patients. As Gallo
demonstrates, there are multiple obstacles, unsolved by Appellants, to
obtaining a successful HIV vaccine (FF 17). Even in the in vitro example
argued as routine, Appellants do not address concerns with vaccinating
immunocompromised individuals who fall within the scope of claim 1 (FF 6,
23, 24). Moreover, Appellants claim encompasses any time of
administration of vaccinia prior to HIV exposure, whether 1 day or 40 years,
and there is only a single working example showing diminishing replication
3 to 6 months after vaccination (FF 2).
Appellants contend that "one of ordinary skill would believe that
treating R5 variants by diminishing the replication at least of CCR5- tropic
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HIV would have a significant clinical effect and would be reasonably
predictive of clinical efficacy" (App. Br. 13).
We find this argument unpersuasive. Appellants state, but provide no
evidence, that diminishing HIV replication of CCR5 tropic virus would be
predictive of clinical efficacy. There is no evidence that even in the patients
tested in the working example, the vaccination demonstrated any clinical
efficacy. Appellants' reliance on Vanpouille is also unavailing (see App. Br.
12-13), because Vanpouille is solely drawn to an in vitro coinfection
scenario, where the vaccinia virus competes for CCR5+ cells with HIV (FF
8, 10) and provides no guidance as to clinical efficacy in actual patients
pretreated with vaccinia virus days, months, or years prior to HIV infection
as encompassed by claim 1.
Appellants contend that "two working embodiments illustrate
statistically significant tests for diminishing the replication of HIV" (App.
Br. 13). Appellants contend that
the statistically significant data from the two working examples
bolsters the credibility of the Appellant's asserted usefulness,
shows success, and/or leads one of ordinary skill to have a
reasonable expectation of success that administering vaccinia
virus is effective at diminishing the replication at least of
CCR5-tropic HIV in a subject.
(App. Br. 14).
We do not find this argument persuasive. While Appellants do have a
working example (not two), demonstrating an in vitro result on patients
vaccinated 3 to 6 months prior that diminishes CCR5 tropic HIV using a
single strain of vaccinia virus (FF 2-3), as already extensively discussed,
this working example is not commensurate in scope with the claim along a
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variety of dimensions. Moreover, Appellants provide no evidence that
diminishing replication in PBMCs represents a model system that would
have been expected to evidence clinical efficacy. Appellants provide no
clinical evidence that diminishing CCR5 tropic virus will have a clinical
effect and Clapham teaches that "CCR5 and CXCR4 are the major co-
receptors and all HIV- I isolates can use one or both" (FF 21 ), suggesting
that blocking CCR5 will not prevent infection using the CXCR4 receptor.
We therefore agree with the Examiner that:
this simple example does not constitute a proper working
embodiment because it is not reasonably predictive of clinical
efficacy. First, none of the subjects in this study were HIV-1-
infected. Thus, the study never measured reductions in patient
viral load, which tend to be more predictive of a positive
clinical outcome. Second, this study does not accurately
reproduce the environment where HIV-1 is most likely to be
transmitted (e.g., in the mucosal tissues of the gut). HIV-1
replicates preferentially in CD4 +ccR5+ macrophages and
lymphocytes of the gut-associated lymphoid tissue (GALT).
This compartment is not in equilibrium with cells of the
lymphatic compartment. Thus, the skilled artisan could
measure viral replication in PBMCs, conclude that little virus
replication had occurred, and miss active viral replication in the
GALT. Third, this study did not address the duration and
magnitude of any putative positive effect associated with
vaccinia vaccination.
(Ans. 6).
Appellants contend that
assuming arguendo any experimentation is necessary,
Appellant's specification provides a reasonable amount of
guidance to enable one of ordinary skill in the art to assess
relevant study parameters and ascertain the response (e.g.,
diminishing and/or reducing HIV replication by administering a
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replication-competent vaccinia virus to diminish the replication
at least of CCR5-tropic HIV).
(App. Br. 16).
We are not persuaded. The guidance in the Specification is simply an
invitation to experiment further to determine what parameters, if any, will
actually result in clinical efficacy. The Specification provides no specific
guidance on the degree of exposure to HIV that will allow efficacy without
killing or sickening immunocompromised infected individuals (FF 23-24).
The Specification provides no specific guidance on the duration, if any, of
protection provided by immunization with vaccinia virus for HIV, nor the
degree of any such protection, only providing generic, non-specific
information on immunization schedules (FF 7). The Specification provides
no guidance on whether reduction in replication of CCR5 tropic viruses will
provide any substantive meaningful clinical protection against HIV CCR5
tropic strains, much less dual tropic strains that infect other receptors such as
CXCR4 (FF 21). See, e.g., Wright, 999 F.2d at 1562 ("[M]any of the
appealed claims encompass vaccines against AIDS viruses and that, because
of the high degree of genetic, antigenic variations in such viruses, no one has
yet, years after his invention, developed a generally successful AIDS virus
vaccine.") McMichael evidences that even as recently as 2006, several years
after the instant priority date, "despite increasingly intense efforts,
development of a [HIV] vaccine is still a long way off' (FF 18).
Appellants contend that "Appellant's specification provides plausible
scientific principles to guide one of ordinary skill in the art as to the
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direction which routine experimentation should proceed by describing
methods, strains, and so on" (App. Br. 19).
We do not find this argument persuasive. The issue is not whether the
scientific principles are plausible because the rejection is not for an
"incredible utility," but rather whether the very broad claim 1 is enabled by
the Specification or whether undue experimentation would have been
required to enable the scope of the claims. The enablement requirement
ensures that "the public knowledge is enriched by the patent specification to
a degree at least commensurate with the scope of the claims." Nat'!
Recovery Techs., Inc. v. Magnetic Separation Sys., Inc., 166 F.3d 1190,
1195-96 (Fed.Cir.1999). The scope of the claims must be "less than or
equal to the scope of enablement." Id. at 1196. For the reasons already
discussed, there are a number of dimensions of significant unpredictable
experimentation that would be required to enable even a minimal scope for
claim 1, and the evidence of record demonstrates that undue experimentation
would have been required to enable a reasonable subset of the embodiments
encompassed by claim 1.
Appellants contend that "one of ordinary skill would know that widely
accepted HIV therapies are useful in combating HIV infection despite the
fact that the virus is usually still present and capable of replicating in the
host" (App. Br. 22).
We find this argument unpersuasive because it lacks any evidentiary
support. See In re Pearson, 494 F.2d 1399, 1405 (CCPA 1974) ("Attorney's
argument in a brief cannot take the place of evidence."). While drugs that
directly inhibit HIV replication, HIV integrase, or HIV protease were known
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at the time of invention, these daily administration therapies that directly act
on HIV proteins differ in kind from a vaccine approach such as the use of
vaccinia virus and provide no guidance as to the expectation of efficacy for
such a vaccine approach. The evidence of record suggests that no HIV
vaccine was effective years after the instant filing date (FF 18) and that there
were significant unresolved obstacles to designing and producing an
effective vaccine (FF 17), evidence that was not persuasively rebutted by
Appellants with contrary evidence.
Appellants contend that
similar to In re Angstadt and Amgen, Appellant's have supplied
data, working examples, a list of possible strains, and processes
for how to use them. Thus, Appellant's enabling disclosure
alone shows success and/or leads one of ordinary skill to have a
reasonable expectation of success that administering vaccinia
virus is effective at diminishing the replication at least of
CCR5-tropic HIV in a subject.
(App. Br. 23).
We are not persuaded. The facts here differ substantially from those
in Angstadt and Amgen. In Angstadt, the claim was to an in vitro chemical
process for catalytic oxidation using a genus of particular hydrocarbons and
the Specification disclosed forty working examples. In re Angstadt, 537
F.2d 498, 502 (CCPA 1976). In Amgen, the claims were to erythropoietin
products and processes of production of those products, with expert
testimony from the party opposing enablement that "if one of ordinary skill
in the art followed the teachings of Example 10, then such a person could
successfully practice the claimed invention." Amgen, Inc. v. Hoechst
Marion Roussel, Inc., 314 F.3d 1313, 1336 (Fed. Cir. 2003).
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Here, the Examiner does not concede enablement, nor is there any
declaration by any party evidencing an expectation that merely following the
teachings of the Example would result in in vivo efficacy in diminishing
HIV replication. Moreover, there is no working example of in vivo
therapeutic efficacy, only a single in vitro example showing that under
particular circumstances there is some reduced level of reverse transcriptase
activity in PBMCs (FF 2-3). Moreover, to replicate Angstadt with other
embodiments within the scope of the claim, the artisan "would merely have
to substitute the correct mass of a transition metal salt for the transition
metal salts disclosed in appellants' 40 runs." Angstadt, 537 F.2d at 503. Cf
Amgen, 324 F.3d at 1336. By contrast, to establish efficacy of the vaccinia
virus treatment in vivo in human patients, expensive randomized clinical
trials in a large number of patients would be required for each different
vaccinia virus, each different immunization regiment, as well as each
different class of patient, whether exposed to HIV, at risk of exposure,
immunocompromised, or undergoing drug treatment, and such clinical trials
are unpredictable (see FF 25). This is the essence of undue experimentation
in an unpredictable, highly complex art, with minimal guidance to direct the
artisan to any embodiments that would be expected to succeed.
Appellants contend that "the breadth of the claims is narrow, directed
to embodiments including diminishing and/or reducing HIV replication by
diminishing at least CCR5 tropic HIV" (App. Br. 24).
We do not find this argument persuasive for the reasons extensively
discussed above. To briefly reiterate, the claim breadth is not narrow but
rather broadly encompasses in vivo treatment of any individual, including
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Application 10/566,586
immunocompromised HIV individuals with any replication competent
vaccinia virus, where the vaccine is administered at any time prior to or after
HIV infection, and where the virus may diminish replication of "at least of
CCR5-tropic HIV," thereby encompassing other HIV not CCR5-tropic.
Conclusion of Law
The evidence of record supports the Examiner's conclusion that the
Specification does not enable the claimed invention.
SUMMARY
In summary, we affirm the rejection of claim 1 under 35 U.S.C. § 112,
first paragraph, scope of enablement. Pursuant to 3 7 C.F .R. § 41.3 7 ( c )( 1 ),
we also affirm the rejection of claims 7-13, 24, and 56-61, 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. § l.136(a).
AFFIRMED
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