Ex Parte Siber

Board of Patent Appeals and Interferences

Nov 20, 2009

10557479 (B.P.A.I. Nov. 20, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________

Ex parte GEORGE R. SIBER
____________

Appeal 2009-013514
Application 10/557,479
Technology Center 1600
____________

Decided: November 20, 2009
____________

Before DONALD E. ADAMS, FRANCISCO C. PRATS, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims 1-12, 15-18, and
25-35, the only claims pending in this application. We have jurisdiction
under 35 U.S.C. § 6(b).

STATEMENT OF THE CASE
The claims are directed to a composition. Claims 1 and 28 are
illustrative:
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1. A composition comprising:
a therapeutically effective amount of an inhibitor of a SARS-
associated inflammatory cytokine in a pharmaceutically acceptable carrier,
wherein said therapeutically effective amount of an inhibitor of a SARS-
associated inflammatory cytokine in a pharmaceutically acceptable carrier is
in an amount sufficient to generate a response that reduces the clinical
impact of the infection in a SARS patient.
28. A composition prepared by a process comprising:
administering a candidate SARS-associated inflammatory cytokine
inhibitor to a group of patients infected by an infectious agent associated
with SARS in a randomized placebo-controlled study;
monitoring the effectiveness of the candidate SARS-associated
inflammatory cytokine inhibitor;
and including a therapeutically effective SARS-associated
inflammatory cytokine inhibitor so identified in a composition with a
pharmaceutically acceptable carrier.

The Examiner relies on the following evidence:
Eberle et al. US 5,635,350 Jun. 3, 1997
Le et al. US 5,656,272 Aug. 12, 1997
Tobinick US 6,419,934 B1 Jul. 16, 2002
Dahiyat et al. US 7,056,695 B2 Jun. 6, 20061

C Y Cheung et al., Induction of proinflammatory cytokines in human
macrophages by influenza A (H5N1) viruses: a mechanism for the unusual
severity of human disease?, 360 Lancet 1831-37 (2002).

1 35 U.S.C. § 102(e) date March 2, 2001.
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K. Lea Sewell, et al., Phase I Trial of ISIS 104838, a 2’-Methoxyethyl
Modified Antisense Oligonucleotide Targeting Tumor Necrosis Factor-α,
303(3) Journal. Pharmacol. Exp. Ther. 1334-43 (2002).

John M Nicholls, et al., Lung pathology of fatal severe acute respiratory
syndrome, 361 Lancet 1773-78 (2003).

The rejections presented by the Examiner follow:
1. Claims 1-12 and 25 stand rejected under 35 U.S.C. § 102(b) as being
anticipated by Tobinick.
2. Claims 15-18 and 26-35 stand rejected under 35 U.S.C § 103(a) as
unpatentable over the combination of Tobinick, Cheung, Nicholls, Eberle,
and Sewell.
We affirm the rejection of claims 1-10, 12, and 25 under 35 U.S.C.
§ 102(b) and the rejection of claims 15 and 28-35 under 35 U.S.C § 103(a).
We reverse the rejection of claim 11 under 35 U.S.C. § 102(b) and the
rejection of claims 16-18, 26, and 27 under 35 U.S.C § 103(a).

Anticipation:
ISSUE

Has Appellant established error in the Examiner’s conclusion that
Tobinick anticipates Appellant’s claimed invention?

FINDINGS OF FACT
FF 1. Appellant’s Specification discloses that “the present invention relates
to compositions comprising inhibitors of tumor necrosis factor (TNF),
including recombinant TNF receptors, small molecules and antibodies”
(Spec. ¶ [001]).
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FF 2. Appellant’s Specification discloses that “[t]he terms ‘TNF receptor’
and ‘TNFR’ refer to proteins having amino acid sequences which are
substantially similar to the native mammalian TNF receptor or TNF binding
protein amino acid sequences, and which are capable of binding TNF
molecules and inhibiting TNF from binding to cell membrane bound TNFR”
(Spec. ¶ [023]).
FF 3. Appellant’s Specification discloses that the term recombinant refers
to “a protein . . . derived from recombinant (e.g., microbial or mammalian)
expression systems” (Spec. ¶ [025]).
FF 4. Appellant’s Specification discloses that “a composition of the
present invention comprises a soluble TNF receptor and preferably a TNFR-
Ig” (Spec. ¶ [046]). In this regard, Appellant’s Specification discloses that
“the TNFR-Ig is TNFR:Fc” (Spec. ¶ [050]).
FF 5. Appellant’s Specification discloses an exemplary regimen for
treating adult human patients that comprises the subcutaneous administration
of a composition comprising 25 mg of TNFR:Fc (id.). More generally,
Appellant’s Specification discloses that SARS (severe acute respiratory
syndrome) treatment can be obtained by the daily administration of a
composition comprising 0.1 to 100 mg/kg of anti-TNF peptides, monoclonal
chimeric and/or routine antibodies of the present invention 0.1 to 100 mg/kg
(Spec. ¶ [131]).
FF 6. Alternatively, Appellant’s Specification discloses that the foregoing
composition can be administered “at least one of week . . . [1-20], or any
combination thereof, using single or divided doses of every 24, 12, 8, 6, 4, or
2 hours, or any combination thereof” (id.).
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FF 7. Appellant’s Specification discloses that “[v]arious other
medicaments used to treat the diseases described herein may also be
administered concurrently with compositions comprising TNF-α inhibitors,
such as TNFR:Fc” (Spec. ¶ [051]). In this regard, Appellant’s Specification
teaches that “compositions of the invention additionally comprise . . .
FAMCICOLVIR [sic]” (Spec. ¶ [118]). More specifically, Appellant’s
Specification teaches that “compositions of the invention are used in any
combination with . . . FAMCICOLVIR [sic] to prophylactically treat or
prevent an opportunistic herpes simplex virus type I and/or type II infection”
(Spec. ¶ [119]).
FF 8. Appellant’s Specification discloses that:
The phrase “therapeutically effective amount,” as used herein,
refers to the amount to be administered to a mammalian host
(preferably human) in each single dose (as part of a series of
doses) to at least cause the individual treated to generate a
response that reduces the clinical impact of the infection. This
may range from a minimal decrease in pathogenic burden to
prevention of the infection. . . . The dosage amount can vary
depending upon specific conditions of the individual.

(Spec. ¶ [030].)

FF 9. The Examiner finds that Tobinick teaches the TNF antagonist
“etanercept” which is a “human soluble TNF receptor linked to the Fc
component of human immunoglobulin G1 (IgG1) and acts as a TNF
inhibitor” (Ans. 5; see also Spec. ¶ [0058]).
FF 10. The Examiner finds that etanercept “incorporates the p75 receptor
protein that binds not only to TNF-α but also to the inflammatory cytokine
LT-α (which is a synonym for TNF-β) [; therefore] etanercept can act as a
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competitive inhibitor not only of TNF-α but also of TNF-β” (id.; see also
Spec. ¶ [0058]).
FF 11. Tobinick teaches the subcutaneous administration of a composition
comprising 2 mg of etanercept together with the oral administration of
Famciclovir (Tobinick, col. 6, ll. 39-42; see also Ans. 6 (“Tobinick also
teach the association of his treatment with antiviral compounds”)).
FF 12. The Examiner finds that Tobinick teaches compositions comprising
“infliximab (which is a chimeric monoclonal antibody) and D2E7 (a human
anti-TNF monoclonal antibody . . .) (Ans. 5). More generally, Tobinick,
teaches the administration of a therapeutically effective dosage level of a
TNF antagonist selected from the group consisting of etanercept, infliximab,
and D2E7 together with a therapeutically effective dosage level of an
antiretroviral agent or agents (Tobinick, claim 49).
FF 13. Appellant’s Specification defines the term “chimeric antibody” as
including “monovalent, divalent or polyvalent immunoglobulins” (Spec. ¶
[028]).
FF 14. Tobinick teaches an infliximab composition comprising infliximab
in a concentration range of 0.1 mg/kg to 5 mg/kg (Tobinick, claim 27).

PRINCIPLES OF LAW
On appeal to this Board, Appellants must show that the Examiner has
not sustained the required burden of making a prima facie case of
unpatentability. See Ex parte Yamaguchi, 88 USPQ2d 1606, 1608 and 1614
(BPAI 2008) (precedential).
“A claim is anticipated only if each and every element as set forth in
the claim is found, either expressly or inherently described, in a single prior
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art reference.” Verdegaal Bros. v. Union Oil Co. of California, 814 F.2d
628, 631 (Fed. Cir. 1987). “Under the principles of inherency, if the prior
art necessarily functions in accordance with, or includes, the claimed
limitations, it anticipates.” In re Cruciferous Sprout Litig., 301 F.3d 1343,
1349 (Fed. Cir. 2002) (citations and internal quotation marks omitted).
“Inherency, however, may not be established by probabilities or
possibilities. The mere fact that a certain thing may result from a given set
of circumstances is not sufficient.” In re Robertson, 169 F.3d 743, 745 (Fed.
Cir. 1999) (citations and internal quotation marks omitted).
“[A] prima facie case of anticipation [may be] based on inherency.”
In re King, 801 F.2d 1324, 1327 (Fed. Cir. 1986). Once a prima facie case of
anticipation has been established, the burden shifts to the Appellant to prove
that the prior art product does not necessarily or inherently possess the
characteristics of the claimed product. In re Best, 562 F.2d 1252, 1255
(CCPA 1977) (“Where, as here, the claimed and prior art products are
identical or substantially identical, or are produced by identical or
substantially identical processes, the PTO can require an applicant to prove
that the prior art products do not necessarily or inherently possess the
characteristics of his claimed product.”); see also In re Spada, 911 F.2d 705,
708-09 (Fed. Cir. 1990) (”[W]hen the PTO shows sound basis for believing
that the products of the applicant and the prior art are the same, the applicant
has the burden of showing that they are not.”).
Arguments not made are waived. See 37 C.F.R. § 41.37(c)(1)(vii).
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ANALYSIS
Appellant presents separate arguments for the following groups of
claims: I. Claims 1-3, 5, 6, 9, and 10; II. Claim 4; III. Claim 7; IV. Claim 8;
V. Claim 11; and VI. Claim 12. Therefore, we limit our discussion to
representative claims 1, 4, 7, 8, 11, and 12. 37 C.F.R. § 41.37(c)(1)(vii).

Claim 1:
We are not persuaded by Appellant’s contention that “Tobinick does
not anticipate the claims because a dosage of a TNFα antagonist effective
for the treatment of a neurological condition would not necessarily be
effective for the treatment of SARS” (App. Br. 9).
As an initial matter, we note that Appellant’s claim 1 is directed to a
composition, not a method of treating SARS. Accordingly, Appellant’s
claim 1 requires (a) that the composition comprises an inhibitor of a SARS-
associated inflammatory cytokine in a pharmaceutically acceptable carrier
and (b) that the composition be in an amount sufficient to generate a
response that reduces the clinical impact of the infection in a SARS patient.
Appellant’s Specification discloses that an inhibitor of a SARS-
associated inflammatory cytokine includes recombinant TNF receptors and
antibodies (FF 1). Appellant’s Specification discloses that the inhibitor may
be TNFR:Fc (FF 4). Appellant’s Specification discloses that such a
TNFR:Fc is known in the art as etanercept (FF 10). Appellant’s
Specification discloses that the composition administered subcutaneously to
generate a response that reduces the clinical impact of the infection in a
SARS patient comprises 25 mg of TNFR:Fc (FF 5).
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Tobinick teaches a composition comprising etanercept (FF 9).
Tobinick teaches a composition, intended for subcutaneous administration,
that comprises 25 mg of etanercept (FF 9). Accordingly, Tobinick teaches a
composition that meets the requirements of claim 1.
Claim 4:
Claim 4 depends from and further limits claim 1 to require that the
inhibitor of tumor necrosis factor is a TNF recombinant receptor (Claim 4).
For the same reasons set forth with regard to claim 1, we are not
persuaded by Appellant’s contention that Tobinick “fails to teach a TNF
recombinant receptor in an amount sufficient to generate a response that
reduces the clinical impact of the infection in a SARS patient” (App. Br. 10).
Appellant failed to establish a difference between the teachings of Tobinick
and the requirements of claim 4.

Claim 7:
Claim 7 ultimately depends from and further limits claim 1 to require
that the SARS-associated inflammatory cytokine is an inhibitor of TNF-β
(Claim 7).
“[E]tanercept can act as a competitive inhibitor not only of TNF-α but
also of TNF-β” (FF 10). Therefore, for the reasons set forth with regard to
claim 1, we are not persuaded by Appellant’s contention that “Tobinick fails
to teach any inhibitor of TNF- β” (App. Br. 11). Appellant failed to
establish a difference between the teachings of Tobinick and the
requirements of claim 7.

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Claim 8:
Claim 8 depends from and further limits claim 1 to require that “the
inhibitor of the SARS-associated inflammatory cytokine is a soluble
recombinant receptor” (Claim 8).
Appellant’s Specification teaches that TNFR:Fc is a soluble TNF
receptor (FF 4). Therefore, for the reasons set forth with regard to claim 1,
we are not persuaded by Appellant’s contention that Tobinick “fails to teach
any soluble recombinant receptor in an amount sufficient to generate a
response that reduces the clinical impact of the infection in a SARS patient”
(App. Br. 11). Appellant failed to establish a difference between the
teachings of Tobinick and the requirements of claim 8.

Claim 11:
Claim 9 ultimately depends from and further limits the inhibitor of
claim 1 to a polyclonal antibody (Claim 9).
Appellant contends that Tobinick fails to teach a polyclonal antibody
(App. Br. 11). We agree.
We recognize the Examiner’s reference to the Le patent cited by
Tobinick to support the assertion that the term “antibody” is a generic term
that includes polyclonal antibodies (Ans. 12). The Examiner’s evidence and
rationale does not, however, establish that Tobinick teaches “antibodies”
generically. As the Examiner carefully points out, Tobinick teaches
compositions comprising monoclonal chimeric antibody infliximab or the
monoclonal antibody D2E7 (FF 12). The Examiner has failed to identify a
teaching in Tobinick of a polyclonal antibody or a composition comprising
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such a polyclonal antibody in the concentration required by Appellant’s
claimed invention.
Since Tobinick fails to teach a polyclonal antibody - each and every
element of claim 11 is not expressly or inherently described in a single prior
art reference as required under 35 U.S.C. § 102. See Verdegaal Bros. v.
Union Oil Co. of California, 814 F.2d at 631. Accordingly, Tobinick fails to
anticipate Appellant’s claim 11.

Claim 12:
Claim 12 ultimately depends from and further limits the inhibitor of
claim 1 to a chimeric antibody (Claim 12).
Tobinick teaches a composition comprising the chimeric antibody –
infliximab in a concentration range of 0.1 mg/kg to 5 mg/kg (FF 12 and 14).
Appellant’s Specification discloses compositions comprising 0.1 to 100
mg/kg of a chimeric antibody (FF 5). Accordingly, we are not persuaded by
Appellant’s contention that Tobinick “fails to teach any chimeric antibody in
an amount sufficient to generate a response that reduces the clinical impact
of the infection in a SARS patient” (App. Br. 12). Appellant failed to
establish a difference between the teachings of Tobinick and the
requirements of claim 12.

CONCLUSION OF LAW
Appellant failed to establish error in the Examiner’s conclusion that
Tobinick anticipates Appellant’s claims 1, 4, 7, 8, and 12. The rejection of
claims 1, 4, 7, 8, and 12 under 35 U.S.C. § 102(b) as being anticipated by
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Tobinick is affirmed. Claims 2, 3, 5, 6, 9, 10, and 25 fall together with claim
1.
Appellant established error in the Examiner’s conclusion that
Tobinick anticipates Appellant’s claim 11. The rejection of claim 11 under
35 U.S.C. § 102(b) as being anticipated by Tobinick is reversed.

Obviousness:
ISSUE

Has Appellant established error in the Examiner’s prima facie case of
obviousness?

FINDINGS OF FACT
FF 15. The Examiner finds that Tobinick fails to teach a composition that
additionally comprises “an anti-coronaviral compound which is an inhibitor
of viral RNA dependent RNA polymerase” (Ans. 6).
FF 16. The Examiner finds that Nicholls teaches that “in the SARS and
SARS-CoV cases, there is an increase in the macrophages in the lung and it
may be that . . . cytokine deregulation may account for the severity of the
disease” (Ans. 6 ).
FF 17. The Examiner finds that Cheung teaches “that the H5N1/97 viruses
are potent inducers of TNF-α in macrophages and this characteristic may
contribute to the unusual severity of the H5N1 human disease” (Ans. 7
(emphasis removed)).
FF 18. The Examiner finds that Eberle teaches:
[A] method of detecting a polymerase activity . . . that can be
employed in any field where such a polymerase activity reveals
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information on the composition of a sample. [That] [t]he
method could be used to test substances for their possible
inhibitory effect on polymerases . . . and indicates a possible
therapeutic use of the substance as an anti-bacterial or anti-viral
agent.

(Id.)
FF 19. The Examiner finds that Sewell teaches “a Phase I clinical trial
evaluating the safety and pharmacokinetics of . . . [an] antisense
oligonucleotide . . . that binds TNF . . . [and] suggest[s] the possibility of
obtaining effective TNF inhibitors by clinical trials” (Ans. 7).

PRINCIPLES OF LAW
In proceedings before the Patent and Trademark Office, the Examiner
bears the burden of establishing a prima facie case of obviousness based
upon the prior art. In re Fritch, 972 F.2d 1260, 1265 (Fed. Cir. 1992). On
appeal to this Board, Appellants must show that the Examiner has not
sustained the required burden. See Ex parte Yamaguchi, 88 USPQ2d 1606,
1608 and 1614 (BPAI 2008) (precedential); Ex parte Fu, 89 USPQ2d 1115,
1118 and 1123 (BPAI 2008) (precedential).
“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).
When there is a design need or market pressure to solve a
problem and there are a finite number of identified, predictable
solutions, a person of ordinary skill has good reason to pursue
the known options within his or her technical grasp. If this
leads to the anticipated success, it is likely the product not of
innovation but of ordinary skill and common sense. In that
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instance the fact that a combination was obvious to try might
show that is was obvious under § 103.

Id. at 421. Nevertheless, “it can be important to identify a reason that would
have prompted a person of ordinary skill in the relevant field to combine the
elements in the way the claimed new invention does.” KSR Int’l Co. v.
Teleflex Inc., 550 U.S. at 418 (2007).
Arguments not made are waived. See 37 C.F.R. § 41.37(c)(1)(vii).

ANALYSIS
Appellant separately argues the following groups of claims: I. Claim
15; II. Claim 16; III. Claims 17, 26, and 27; IV. Claim 18; and V. Claims 28-
35. Therefore, we limit our discussion to representative claims 15-18 and
28. 37 C.F.R. § 41.37(c)(1)(vii).

Claim 15:
Claim 15 depends from and further limits claim 1 to additionally
comprise an anti-viral compound in the pharmaceutically acceptable carrier
(Claim 15).
Tobinick teaches a composition comprising etanercept that is
administered in combination therapy with FAMCICLOVIR (FF 11). We
find no persuasive evidence or argument on this record to suggest that a
person of ordinary skill in the art would not have found it prima facie
obvious to combine the two active ingredients into a single composition.
Accordingly, we are not persuaded by Appellant’s contention that “it would
not be obvious to make a composition comprising an ‘anti-viral compound’
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and a ‘therapeutically effective amount of an inhibitor of a SARS-associated
inflammatory cytokine’” (App. Br. 19).

Claims 16-18, 26, and 27:
Claim 16 depends from and further limits the anti-viral compound of
claim 1 [sic, claim 15] to an anti-coronaviral compound.
Appellant contends that “it would not be obvious to make a
composition comprising an ‘anti-coronaviral compound’ and a
‘therapeutically effective amount of an inhibitor of a SARS-associated
inflammatory cytokine” based on the combination of references relied upon
by the Examiner (App. Br. 19). We agree.
The Examiner has failed to identify a teaching in the prior art relied
upon of an anti-coronaviral compound. The Examiner has also failed to
identify a teaching in the prior art relied upon of an inhibitor of viral RNA-
dependent RNA polymerase, an inhibitor of a virus-encoded protease that
affects processing of a viral RNA-dependent RNA polymerase, an inhibitor
of coronavirus budding or release from infected cells that does or does not
affect the activity of hemagglutinin-esterase, an inhibitor of virus binding to
a specific cell surface receptor, or an inhibitor of receptor-induced
conformational changes in virus spike glycoprotein that are associated with
virus entry and combinations thereof (see e.g., Appellant’s claims 17, 18, 26,
and 27). Thus, the Examiner has failed to establish that it would have been
obvious to incorporate such a compound into the composition taught by
Tobinick.
In this regard, while we recognize that Tobinick teaches Famciclovir,
the Examiner has failed to establish an evidentiary basis on this record to
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support a conclusion that Famciclovir would have the properties required by
Appellant’s claimed invention.
At best, the Examiner intimates that it would have been obvious to a
person of ordinary skill in the art to search for such compounds and then, if
found, add them to Tobinick’s composition (see Ans. 7-8). We are not
persuaded. As Appellant points out such a rationale provides “neither a
‘finite number of identified, predictable potential solutions’ nor a
‘reasonable expectation of success’ as is required by KSR” (App. Br. 14).

Claim 28:
Claim 28 is reproduced above and is drafted in product-by-process
language. In sum, the composition of claim 28 comprises a therapeutically
effective SARS-associated inflammatory cytokine inhibitor in a composition
with a pharmaceutically acceptable carrier.
For the reasons set forth above with respect to claim 1, we find that
Tobinick teaches such a composition. We are not persuaded by Appellant’s
contentions with regard to impermissible hindsight, obvious-to-try, or the
failure of others (App. Br. 12-19). In short, Appellant has not provided
persuasive argument or evidence to support a conclusion that Tobinick’s
composition is distinct or non-obvious from Appellant’s composition.

CONCLUSION OF LAW
Appellant failed to establish error in the Examiner’s prima facie case
of obviousness with regard to claims 15 and 28. The rejection of claims 15
and 28 under 35 U.S.C § 103(a) as unpatentable over the combination of
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Tobinick, Cheung, Nicholls, Eberle, and Sewell is affirmed. Claims 29-35
fall together with claim 28.
Appellant established error in the Examiner’s prima facie case of
obviousness with regard to claims 16-18, 26, and 27. The rejection of
claims 16-18, 26, and 27 under 35 U.S.C § 103(a) as unpatentable over the
combination of Tobinick, Cheung, Nicholls, Eberle, and Sewell is reversed.

TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED-IN-PART

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