Ex Parte Wary et al

Board of Patent Appeals and Interferences

Mar 12, 2010

10812238 (B.P.A.I. Mar. 12, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte KISHORE K. WARY and JOSEPH O. HUMTSOE
__________

Appeal 2009-006644
Application 10/812,238
Technology Center 1600
__________

Decided: March 12, 2010
__________

Before TONI R. SCHEINER, DEMETRA J. MILLS, and
ERIC GRIMES, Administrative Patent Judges.

MILLS, Administrative Patent Judge.

DECISION ON APPEAL

This is an appeal under 35 U.S.C. § 134. The Examiner has rejected
the claims for anticipation and obviousness. We have jurisdiction under 35
U.S.C. § 6(b).

Appeal 2009-006644
Application 10/812,238

STATEMENT OF CASE
The following claims are representative.
8. A method of inhibiting αvβ3 and/or α5β1 integrin ligand-mediated
cell-cell interaction, comprising:
contacting the cells with an antibody directed against a peptide
consisting of SEQ ID NO: 41 or consisting of SEQ ID No. 2 that is derived
from a cell surface vascular endothelial growth factor and type I collagen
inducible protein (VCIP) consisting of SEQ ID No. 13, wherein said contact
with the antibody blocks binding of αvβ3 and/or α5β1 integrins to the cell
surface vascular endothelial growth factor and type I collagen inducible
protein (VCIP), thereby inhibiting the αvβ3 and/or α5β1 integrin ligand-
mediated cell-cell interaction.

15. A method of inhibiting tumor growth, inflammation and/or
angiogenesis in a patient, comprising:
administering to said patient an antibody directed against a peptide
consisting of SEQ ID No. 41 or consisting of SEQ ID No. 2 that is derived
from a cell surface vascular endothelial growth factor and type I collagen
inducible protein (VCIP) consisting of SEQ ID No. 13, wherein said
antibody blocks binding of αvβ3 and/or α5β1 integrins to the cell surface
vascular endothelial growth factor and type I collagen inducible protein
(VCIP), thereby inhibiting tumor growth, inflammation and/or angiogenesis
in the patient.

32. A method of inhibiting angiogenesis and the formation of
capillaries in a patient in need of such a treatment, comprising:
administering to said patient a pharmacologically effective amount of
an antibody directed against a peptide consisting of SEQ ID No. 41 or
consisting of SEQ ID No. 2 that is derived from vascular endothelial growth
factor and type I collagen inducible protein (VCIP) consisting of SEQ ID
No. 13, wherein said antibody inhibits αvβ3 and/or α5β1 integrin-mediated
cell-cell interaction, thereby inhibiting angiogenesis and the formation of
capillaries in the patient in need of a such a treatment.

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Cited References
Hubbell et al. US 5,567,440 Oct. 22, 1996
Cheng et al. US 5,807,819 Sep. 15, 1998

Vassilev et al., Inhibition of Cell Adhesion by Antibodies to Arg-Gly-Asp
(RGD) in Normal Immunoglobulin for Therapeutic Use (Intravenous
Immunoglobulin, IVIg), 93 BLOOD 3624-3631 (1999).

Moise Bendayan, Possibilities of False Immunocytochemical Results
Generated by The Use of Monoclonal Antibodies: The Example of the Anti-
proinsulin Antibody, 43 J. HISTOCHEM. CYTOCHEM. 881-886 (1995).

Appellants provide separate argument for claims 8, 15 and 32, so we
address the subject matter of each of these independent claims.

Grounds of Rejection
1. Claims 8 and 14-15 are rejected under 35 U.S.C. § 102(b) as being
anticipated by Vassilev as is evidenced by Bendayan.
2. Claims 15 and 32 are rejected under 35 U.S.C. § 103(a) as being
unpatentable over Cheng, Hubbell and Vassilev as evidenced by Bendayan.

FINDINGS OF FACT
1. The Examiner finds that: “Vassilev et a1 teach that RGD motif has a
central role in mediating cell-to-cell adhesion in a variety of immunological
and inflammatory processes (see page 3629, bridging ¶ and page 3624, 2nd
col., lst full ¶ in particular).” (Ans. 3.)
2. The Examiner finds that
Vassilev et a1 teach that IVIg contains antibodies to Arg-Gly-
Asp (RGD) sequence, and the attachment site of a number of
adhesive extracellular matrix proteins, including ligands for β1,
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β3 and β5 integrins (see abstract). Vassilev et a1 teach a
method of inhibiting integrin-dependent platelet aggregation
(cell-cell) to fibronectin (Fn) (ligand) “integrin ligand-mediated
cell-cell interaction” by anti-RGD antibodies (see page 3626,
1st col., 2nd paragraph and Fig. 4 in particular).

(Id.)
3. The Examiner finds that
Further, adhesion of thrombin-stimulated platelets to von
Willebrand factor or Fg (integrin ligand-mediated cell-cell
interaction) was completely inhibited by affinity-purified anti-
RGD antibodies. Vassilev et a1 teach that the presence of
natural IgG antibodies to the RGD motif may contribute to the
immunomodulatory and anti-inflammatory effects of the
therapeutic preparations of normal IgG (see abstract). Vassilev
et a1 teach that affinity purified anti-RGD antibodies block the
adhesion of Raji cells to Fn. By inhibiting leukocyte adhesion,
antibodies in IVIg that recognize the RGD adhesion motif may
contribute to the anti-inflammatory effects of IVIg (see page
3629, top ¶).

(Id. at 3-4.)
4. Vassilev “teaches that the inhibition of cell adhesion by anti-RGD
antibodies can be critical in the Fn matrix formation involving α5/β1
integrins and the subsequent cell adhesion in the progression
of metastasis (see page 3629,2nd co., lst full ¶).” (Ans. 4.)
5. Vassilev “teach that the MoAbs to integrins and adhesion-blocking
peptides have been used in experimental models of autoimmune and
inflammatory disease as well as the treatment of patients with solid organ
allograft rejection (see page 3629, 2nd col. 2nd ¶ in particular).” (Id.)
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6. Vassilev “teaches that the anti-RGD antibodies bind to peptide and
proteins expressing the RGD sequence (see page 3625, 1st col., under
Binding assays).” (Id.)
7. Vassilev teaches that “the RGD fraction of IVIg bound to fibronectin,
fibrinogen, vitronection, VWF and laminin in a dose dependent manner (see
Fig. 1 and page 3626, col., 1, top ¶).” (Id.)
8. The Examiner finds that, “[g]iven that the claimed SEQ ID NO: 2 and 41
are RGD-containing peptide sequences, the referenced anti-RGD antibodies
would bind to the claimed SEQ ID NO: 2 (EGYIQNYRCRGDDSK-
VQEAR) and 41 (CRGDD). Moreover, antibodies ‘cross-react’ with
antigens with homolgous [sic] amino acid residues.” (Id.)
9. Vassilev’s “anti-RGD antibody would bind to the peptide comprises SEQ
ID NO: 41 (CRGDD) and 2 (EGYIQNYRCRGDDSKVQEAR) due to the
shared sequence homology (RGD motif).” (Id.)
10. The Examiner finds that
As is evidenced by Bendayan (J. Histochem. Cytochem.
1995,43:881-886) who characterizes the specific reactivity of a
monoclonal antibody produced to human proinsulin, and shows
that although the antibody is highly specific, it is nevertheless
able to bind to not only human proinsulin, but to proinsulin
from other species and even a distinct protein, glucagons, based
upon conservation of an Arg-Arg dipeptide sequence in each of
these molecules (see entire document).

(Ans. 4.)
11. “Bendayan concludes that ‘an antibody directed against such a
sequence, although still yielding specific labeling, could reveal different
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molecules not related to the original antigen’ (page 886, last paragraph in
particular).” (Id. at 4-5.)
12. The Examiner finds that
While the prior art teachings may be silent as to the “antibody
blocks binding of αvβ3 and/or α5β1 integrins to the cell surface
VCIP” per se; the method and the product used in the reference
method are the same as the claimed method. Therefore
“antibody blocks binding of αvβ3 and/or α5β1 integrins to the
cell surface VCIP” is considered inherent properties. The anti-
RGD antibodies administered bind to a ligand comprising the
RGD motif due to properties inherently possessed by the
antibody. That is the mechanism of action does not have a
bearing on the patentability of the invention if the invention
was already known or obvious.

(Id. at 5.)
13. “The ‘819 [Cheng] patent teaches a method of treating angiogenesis
comprising administering to the subject RGD-containing peptides (agents)
(see abstract and the entire document).” (Id. at 6.)
14. “The ‘819 [Cheng] patent further teaches that angiogenesis is required
for the growth of solid tumors and neovascularization serves as a conduit for
metastasis (see col. 9, lines 19-21 in particular).” (Id.)
15. The Examiner finds that
Further, the ‘819 [Cheng] patent teaches methods of using the
Arg--Gly--Asp containing peptides such as CRGDDVC
(patented SEQ ID NO: 17) to alter αvβ3 integrin receptor-
mediated binding of a cell . . . to a matrix. The ‘819 [Cheng]
patent teaches further teaches methods for ameliorating the
severity of a pathology characterized by an undesirable level of
angiogenesis in a subject using RGD-containing peptides (see
the entire document including the abstract).

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(Ans. 6.)
16. “The claimed invention differs from the ‘819 [Cheng] patent teachings
only by the recitation of antibody to SEQ ID NO: 2 or 41 in claims 15 and
32.” (Id.)
17. “The ‘440 [Hubbell] patent teaches that cell adhesion plays an important
role in human disease. These interactions proceed by the interaction of
receptors upon the surface of a cell with proteins or glycosaminoglycans
upon the surface of another cell or within the extracellular matrix.” (Id.)
18. “The ‘440 [Hubbell] patent further teaches that routes to the interruption
of these interactions typically involve competitive inhibition of these
receptor-ligand interactions, for example, with antibodies, soluble ligands
which act as receptor antagonists (e.g., cyclic RGD peptides), soluble
receptors, or other competitors (see col. 1, lines 17-30 in particular).” (Id.)
19. “Vassilev et a1 teach a method of inhibiting integrin-dependent platelet
aggregation ‘cell-cell interaction’ to Fn (integrin ligand-mediated cell-cell
interaction) by anti-RGD antibodies (see page 3626, lst col., 2nd paragraph
and Fig. 4 in particular).” (Id.)
20. The Examiner finds that “Vassilev et a1 further teach that . . . cyclic
RGD peptides have been shown to inhibit α4β1-dependent adhesion of T
cells to cytokine-activated endothelial cells (see page 3629, lst col., last
paragraph to the 2nd col., 1st paragraph in particular).” (Ans. 6-7.)
21. “The limitation ‘blocks the binding of αvβ3 and/or α5βl integrins to cell
surface VCIP’ would be expected properties of the resultant method.” (Id. at
7.)
22. The Examiner finds that “[i]t would have been obvious to one of
ordinary skill in the art at the time the invention was made to substitute the
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CRGDDVC cyclic peptide taught by the ‘819 [Cheng] patent with anti-RGD
antibody taught by Vassilev et a1 in a method of inhibiting angiogenesis in a
subject.” (Id.)
23. The Examiner finds that
One of ordinary skill in the art at the time the invention was
made would have been motivated to do so because routes to the
interruption of cell-cell interactions typically involve
competitive inhibition of these receptor-ligand interactions with
either receptor antagonists (e.g., cyclic RGD peptides),
antibodies or other competitors as taught by the ‘440 [Hubbell]
patent.

(Ans. 7.)
24. The Examiner finds from the combined teachings of the references,
“that one of ordinary skill in the art would have had a reasonable expectation
of success in producing the claimed invention.” (Id.)

Claim Interpretation
During ex parte prosecution, claims are to be given their broadest
reasonable interpretation consistent with the description of the invention in
the specification. See In re Zletz, 893 F.2d 319, 321 (Fed. Cir. 1989).
“Without evidence in the patent specification of an express intent to
impart a novel meaning to a claim term, the term takes on its ordinary
meaning.” Optical Disc Corp. v. Del Mar Avionics, 208 F.3d 1324, 1334
(Fed. Cir. 2000). In addition, “[t]he ordinary and customary meaning of a
claim term may be determined by reviewing a variety of sources. Some of
these sources include the claims themselves; dictionaries and treatises; and
the written description, the drawings, and the prosecution history.”
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Brookhill-Wilk, LLC v. Intuitive Surgical, Inc., 334 F.3d 1294, 1298 (Fed.
Cir. 2003).
The steps of the method of claim 8 include:
contacting cells with an antibody “directed against” a peptide consisting of
SEQ ID NO: 41 or consisting of SEQ ID No. 2.
The term “directed against,” in the context of antibody/antigen
binding, means that an antibody binds to a particular antigen. Thus, we
conclude that an antibody within the scope of the claim must have cross-
reactivity with a peptide consisting of SEQ ID NO: 41 or consisting of SEQ
ID No. 2, since Appellants have provided no special definition of the term
“directed against” in the Specification.

Anticipation
1. Claims 8 and 14-15 are rejected under 35 U.S.C. § 102(b) as being
anticipated by Vassilev as is evidenced by Bendayan.

ISSUE
The Examiner finds that Vassilev discloses each element claimed.
Appellants contend that Vassilev does not teach a method of
inhibiting tumor growth, inflammation, and/or angiogenesis in a patient.
Appellants argue that Vassilev does not teach blocking the interaction
between αvβ3 and/or α5β1 integrins to the cell surface vascular endothelial
growth factor and type I collagen inducible protein (VCIP), thereby
inhibiting the αvβ3 and/or α5β1 integrin ligand-mediated cell-cell
interaction.
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The issue is: Have Appellants demonstrated error in the Examiner’s
anticipation rejection?

PRINCIPLES OF LAW
In order for a prior art reference to serve as an anticipatory reference,
it must disclose every limitation of the claimed invention, either explicitly or
inherently. See In re Schreiber, 128 F.3d 1473, 1477 (Fed. Cir. 1997).
Moreover:

Where . . . 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…. Whether the rejection is based on “inherency” under
35 U.S.C. § 102, on “prima facie obviousness” under 35 U.S.C.
§ 103, jointly or alternatively, the burden of proof is the same,
and its fairness is evidenced by the PTO’s inability to
manufacture products or to obtain and compare prior art
products.

In re Best, 562 F.2d 1252, 1255 (CCPA 1977) (emphasis added).

“From the standpoint of patent law, a compound and all of its
properties are inseparable; they are one and the same thing.” In re Papesch,
315 F.2d 381, 391 (CCPA 1963).

Principles of Law for remaining obviousness rejections
“In rejecting claims under 35 U.S.C. § 103, the examiner bears the
initial burden of presenting a prima facie case of obviousness. Only if that
burden is met, does the burden of coming forward with evidence or
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argument shift to the applicant.” In re Rijckaert, 9 F.3d 1531, 1532 (Fed.
Cir. 1993) (citations omitted). In order to determine whether a prima facie
case of obviousness has been established, we consider the factors set forth in
Graham v. John Deere Co., 383 U.S. 1, 17 (1966): (1) the scope and content
of the prior art; (2) the differences between the prior art and the claims at
issue; (3) the level of ordinary skill in the relevant art; and (4) objective
evidence of nonobviousness, if present.
“[O]bviousness requires a suggestion of all limitations in a claim.”
CFMT, Inc. v. Yieldup Int’l Corp., 349 F.3d 1333, 1342 (Fed. Cir. 2003)
(citing In re Royka, 490 F.2d 981, 985 (CCPA 1974)).
“[W]hen unexpected results are used as evidence of nonobviousness,
the results must be shown to be unexpected compared with the closest prior
art.” In re Baxter-Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991).

ANALYSIS
Appellants contend that Vassilev does not teach a method of
inhibiting tumor growth, inflammation, and/or angiogenesis in a patient.
(App. Br. 12.) Appellants argue that Vassilev does not teach blocking the
interaction between αvβ3 and/or α5β1 integrins to the cell surface vascular
endothelial growth factor and type I collagen inducible protein (VCIP),
thereby inhibiting the αvβ3 and/or α5β1 integrin ligand-mediated cell-cell
interaction. Appellants also argue that Vassilev does not teach the specific
peptide sequences of SEQ ID NOs: 2 and 41. (App. Br. 12.)
We essentially agree with the Examiner’s fact finding, statement of
the rejection and responses to Appellants’ arguments as set forth in the
Answer. We adopt them as our own. In particular, with respect to
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Appellants’ arguments for integrin binding of claim 8 and for tumor growth
and inflammation for claim 15, the Examiner responds that:
Vassilev et al teach the ability of the anti-RGD antibodies in
IVIg to inhibit integrin-dependent platelet aggregation to
fibronectin (Fn) (integrin ligand-mediated cell-cell interaction)
(see Fig. 4, page 3627). . . . Specifically, Vassilev et a1 teach
IVIg contains antibodies to the Arg-Gly-Asp (RGD) sequence,
and the attachment site of a number of adhesive extracellular
matrix proteins, including ligands for β1, β3 and β5 integrins.
Anti-RGD F(ab')2 antibodies inhibited the adhesion of activated
α4β1 integrin-expressing B cells to Fn. . . . Regarding tumor
growth, claim 15 recites the conditions “tumor growth,
inflammation and/or angiogenesis” in the alternative. In this
case, there is no requirement for the prior art to meet all the
claimed conditions. Yet, Vassilev teach that integrins play a
critical role in inflammation, immune responses, thrombosis,
malignant transformation, and metastasis (see page 3624, 2nd
col., lst ¶). [“]Metastasis formation was shown to be suppressed
by agents interfering with RGD-dependent adhesion in several
animal models and in vitro models by using human tumoral
cells. MoAbs to integrins and adhesion-blocking peptides have
been used in experimental models of autoimmune and
inflammatory diseases as well as in the treatment of patients
with solid organ allograft rejection. Because human IgG
autoantibodies recognizing the same target molecules as these
MoAbs are present in IVIg, we speculate that IVIg may have
similar in vivo effects[”] (see p. 3629, 1st full ¶).

(Ans. 8-9.)

Thus, Vassilev teaches an antibody to a sequence, RGD. The method
of Claim 8 requires contacting cells with an antibody with cross-reactivity to
SEQ ID NO: 41 (“CRGDD”). We conclude that the Examiner has provided
sufficient evidence that the Vassilev antibody to the RGD sequence would
have the same or substantially the same cross-reactivity and integrin binding
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as the claimed antibody to “CRGDD” to shift the burden of proof under In
re Best, to provide evidence that the two antibodies do not possess the same
properties or ability to inhibit αvβ3 and/or a5β1 integrin ligand-mediated
cell-cell interaction. Appellants have not provided evidence that the
Vassilev antibodies and the claimed antibodies do not possess the same
properties or ability to inhibit αvβ3 and/or a5β1 integrin ligand-mediated
cell-cell interaction of claim 8, or anti-tumor or anti-inflammatory properties
of claim 15.
Appellants argue that Vassilev teaches inhibiting platelet aggregation
(App. Br. 11) and that “inhibiting platelet aggregation by a pool of naturally
occurring antibodies is not the equivalent of inhibiting αvβ3 and/or α5β1
integrin ligand-mediated cell-cell interaction nor the same as inhibiting
tumor growth, inflammation and/or angiogenesis in a patient, as recited in
Appellants' claims 8 and 15.” (App. Br. 11.)
The Examiner does not find this argument persuasive because

Vassilev et al teach that these antibodies are relevant for the
immunomodulatory effects of IVIg in autoimmune and
inflammatory diseases and for understanding the role of normal
IgG in immune homestasis (see page 3624, 2nd col., 2nd full ¶)
Vassilev et a1 teach that the RGD motif has a central role in
mediating cell-to-cell and cell-matrix adhesion in a variety of
immunological and inflammatory processes (see page 3629,
bridging ¶). With respect to the antibody, Vassilev et a1 teach
that the anti-RGD antibodies bind to AVTGRGDSPA peptide
and to proteins expressing the RGD sequence, such as the RGD
containing Fn, vitronectin, fg, and vWF (see pp. 3625, 1st col.,
under Binding assays). Given that the claimed SEQ ID NO: 2
and 41 are RGD-containing peptides, wherein the RGD motif
has a central role in mediating cell-to-cell adhesion, the
referenced anti-RGD antibodies would bind to the claimed
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SEQ ID NO: 2 (EGYIQNYRCRGDDSKVQEAR) and 41
(CRGDD) irrespective of how the antibodies were obtained.

(Ans. 9-10.) We agree one of ordinary skill in the art reviewing the
disclosure of Vassilev would understand that the Vassilev antibodies possess
immunomodulatory effects relevant to inflammatory diseases, as in claim
15.
In addition, Appellants argue that “Vassilev et al. do not teach
blocking the interaction between VCIP and the αvβ3 and α5β1 integrins.
Also, Vassilev et al. do not teach VCIP or αvβ3 and/or α5β1 integrins.”
(App. Br. 11.)
We do not find this argument persuasive. The Examiner provides
evidence that:
Although the reference is silent about blocking the binding of
αvβ3 and/or α5β1 integrins to VCIP, it does not appear that the
claim language or limitations result in a manipulative difference
in the method steps when compared to the prior art disclosure.
… On this record, it is reasonable to conclude that the same
patient is being administered the same active anti-RGD
antibodies by the same mode of administration in the same
amount in both the instant claims and the prior art reference.
The fact that applicant may have discovered yet another
beneficial effect from the method set forth in the prior art does
not mean that they are entitled to receive a patent on that
method. The claimed functional limitations would be inherent
properties of the referenced methods to administer anti-RGD
antibodies to treat inflammation. Vassilev et a1 teach that the
RGD motif has a central role in mediating cell-to-cell adhesion
in a variety of immunological and inflammatory process (see
page 3629, bridging ¶) The claimed method recites inhibition of
“αvβ3 and/or α5β1 integrin ligand-mediated cell-cell
interaction”. Vassilev et al teachings the inhibition of platelets
aggregation (cell-cell) to fibronectin (ligand) is integrin ligand-
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mediated cell-cell interaction as recited in the preamble of the
claim. The integrin being αvβ3 and/or α5βl is inherent to the
platelets. Platelets do express both αvβ3 and α5β1 in addition to
the αIIbβ3. [Vassilev, 3626 and 3629.] That is the anti-RGD
antibodies bind to an RGD-containing ligand mediated platelet
aggregation (cell-cell interaction) which would lead to the
inhibition of the aggregation. The integrin being αvβ3, α5βl or
αIIbβ3 is inherent. Both the claimed and the prior art invention
are directed to a single method step of inhibiting integrin
ligand-mediated cell-cell interaction with anti-RGD antibodies.
The prior art anti-RGD antibodies would bind to claimed SEQ
ID NOS: 2 and 41, the cell surface integrins including αvβ3 and
α5β1 that recognize the RGD motif would inherently be
inhibited in the method. The ligand being VCIP, which is an
RGD-containing protein, is inherent in the method which
contributes to inflammation. The teaching of record has
properly shifted burden to applicant.

(Ans. 10-11.)

Appellants argue that their anti-VCIP-RGD antibody does not react
with mouse antigens, referencing the Specification, page 40. (App. Br. 13.)
The Specification does not specifically indicate which mouse antigens their
antibody did not react with. Again, Appellants have not provided appropriate
comparative evidence with the closest prior art, that is, evidence showing
that the Vassilev antibodies do not possess the properties recited in the
claims. No Reply Brief was filed by Appellants in response to the
Examiner’s arguments.

CONCLUSION OF LAW
Appellants have not demonstrated error in the Examiner’s anticipation
rejection.

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Obviousness
2. Claims 15 and 32 are rejected under 35 U.S.C. § 103(a) as being
unpatentable over Cheng, Hubbell and Vassilev as evidenced by Bendayan.

ISSUE
The Examiner finds that it would have been obvious to one of ordinary
skill in the art at the time the invention was made to replace the CRGDDVC
cyclic peptide taught by Cheng with the anti-RGD antibody taught by
Vassilev et a1 in a method of inhibiting angiogenesis in a subject.
Appellants contend that one of ordinary skill in the art would not have
had a reasonable expectation of success of inhibiting tumor growth,
inflammation and/or angiogenesis upon review of the cited references.
(App. Br. 15.) Appellants argue that one of ordinary skill in the art would
not have been able to predict that VCIP would function as an integrin ligand.
The issue is: Have Appellants demonstrated error in the Examiner’s
obviousness rejection?

ANALYSIS
Appellants contend that one of ordinary skill in the art would not have
had a reasonable expectation of success of inhibiting angiogenesis upon
review of the cited references. (App. Br. 15.)
We essentially agree with the Examiner’s fact finding, statement of
the rejection and responses to Appellants’ arguments as set forth in the
Answer.
With respect to claim 32, the Examiner finds that the combined prior
art and Appellants administer the same antibody to the same patient to
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achieve the same results. (Ans. 14-15.) We agree with the Examiner that
one of ordinary skill in the art reviewing the cited references would have
understood that anti-RGD antibodies could be administered to a patient to
inhibit angiogenesis. (See particularly, Cheng, col. 12, ll. 56-61.) We
conclude that the Examiner has provided sufficient evidence that the
antibodies to the RGD sequence of the combination of the cited references
would have the same or substantially the same cross-reactivity and anti-
angiogenesis properties as the claimed antibody to “CRGDD” to shift the
burden of proof under In re Best, to provide evidence that the two antibodies
do not possess the same anti-angiogenesis properties. Appellants have not
provided such evidence. All that is required by the patent law is a
reasonable expectation of success, not absolute predictability of success. See
In re O’Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988). A reasonable
expectation is provided by the combination of the cited references indication
that the anti-RGD antibodies are useful in the treatment of angiogenesis.

CONCLUSION OF LAW
Appellants have not demonstrated error in the Examiner’s obviousness
rejection.
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

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ADLER & ASSOCIATES
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