Ex Parte Bicknell et al

Patent Trial and Appeal Board

Jan 6, 2016

11890213 (P.T.A.B. Jan. 6, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
111890,213 08/02/2007
23628 7590 01/08/2016
WOLF GREENFIELD & SACKS, P.C.
600 ATLANTIC A VENUE
BOSTON, MA 02210-2206
FIRST NAMED INVENTOR
Roy Bicknell
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.
P0357.70001US02 7194
EXAMINER
BRISTOL, LYNN ANNE
ART UNIT PAPER NUMBER
1643
NOTIFICATION DATE DELIVERY MODE
01/08/2016 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):
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ROY BICKNELL, STEVEN SUCHTING,
and LORNA MARY DYET STEWART
Appeal2013-006622
Application 11/890,213
Technology Center 1600
Before MELANIE L. McCOLLUM, JEFFREY N. FREDMAN, and
RICHARD J. SMITH, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal 1 under 35 U.S.C. § 134 involving claims to a method
of treating tumor-associated angiogenesis with a monoclonal antibody. The
Examiner rejected the claims as failing to comply with the written
description requirement. We have jurisdiction under 35 U.S.C. § 6(b). We
reverse.
1 Appellants identify the Real Parties in Interest as Cancer Research
Technology Limited and Genentech, Inc. (see App. Br. 2).
Appeal2013-006622
Application 11/890,213
Statement of the Case
Background
"The process whereby new vessels originate as capillaries, which
sprout from existing small vessels, is called angiogenesis" (Spec. 1, 11. 26-
27). A "deregulation of blood vessel growth and an abnormal increase in
vessel density can occur in diseases or conditions such as tumourigenesis,
diabetic retinopathy, psoriasis and inflammation" (Spec. 2, 11. 5-7).
The Claims
Claims 47, 76, 78, and 79 are on appeal. Independent claim 47 is
representative and reads as follows:
4 7. A method of treating tumor-associated angiogenesis in an
individual in need thereof comprising
administering a monoclonal antibody that selectively
binds to the lg region of magic roundabout (MR)
(corresponding to amino acid residues 46-209, set forth herein
as SEQ ID N0:4) to the individual.
The Issue
The Examiner rejected claims 47, 76, 78, and 79 under 35 U.S.C.
§ 112(a) or 35 U.S.C. § 112 (pre-AIA), first paragraph, as failing to comply
with the written description requirement (Ans. 3-11 ).
The Examiner finds that the "specification and the prior art do not
disclose the genus much less a representative number of anti-MR antibodies
having a structure/function correlation which meet all of the limitations of
the claims" (Ans. 6). The Examiner acknowledges the MR7 working
example, but finds "the rat aortic ring assay a less than ideal choice for
correlating any given anti-MR antibody (structure) effect to angiogenesis
much less tumor-associated angiogenesis (function)" (Ans. 8). The
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Application 11/890,213
Examiner finds "the specification does not identify 1) a complete structure,
ii) partial structure, iii) physical and/or chemical properties, or iv) functional
characteristics coupled with correlation between structure and function for
the method(s) for using the genus of antibodies" (Ans. 8).
The issue with respect to this rejection is: Does the evidence of record
support the Examiner's position that a tumor treatment method comprising
"administering a monoclonal antibody that selectively binds to the lg region
of magic roundabout" fails to satisfy the written description requirement?
Findings of Fact
1. The Specification teaches that "[h ]uman magic roundabout
(MR; also known as endothelial cell-specific molecule 4, ECSM4) has
previously been shown to have a highly endothelial-cell selective expression
profile" (Spec. 4, 11. 9--11 ).
2. The Specification teaches that "WO 02 /36771 teaches a
compound comprising a moiety that binds to MR, such as an antibody, and a
further moiety such as an inhibitor of angiogenesis" (Spec. 4, 11. 27-29).
3. The Specification teaches that:
By "MR" we include the gene product of the human magic
roundabout gene (also known as ECSM4) and naturally
occurring variants thereof. The cDNA and amino acid
sequence of MR are found in Genbank Accession Nos.
AF361473 and AAL31867, and are shown in Figure 1 (SEQ
ID NOs: 1 and 2, respectively).
(Spec. 6, 1. 27 to 7, 1. 2).
4. The Specification teaches that the "extracellular region of MR
has an immunoglobulin (lg) region at residues 46-209 (SEQ ID NO: 4),
which can be further subdefined into an IgA domain at residues 46-116
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Application 11/890,213
(SEQ ID NO: 5), and an IgB domain at residues 151-209 (SEQ ID NO: 6)"
(Spec. 7, 11. 7-10).
5. The Specification teaches that "[i]nhibition of angiogenesis
may be useful in combating any disease or condition involving unwanted,
undesirable or inappropriate angiogenesis. Such conditions include
tumours/cancer" (Spec. 8, 11. 5-7). The Specification further teaches the
"use of an antibody that selectively binds to the extracellular region of MR
in the preparation of a medicament for inhibiting angiogenesis" (Spec. 12, 11.
26-28).
6. The Specification teaches that "hybridomas were tested for their
ability [to] generate antibodies that recognise MR using ELISA. Of the
antibodies identified, one was chosen for further studies -MR 7" (Spec. 69, 11.
16-18).
7. The Specification teaches that "MR7 recognises the MR IgA
domain. The DNA sequence encoding the Complementary Determining
Regions (CD Rs) of MR7 was determined by PCR amplification and
standard sequencing techniques" (Spec. 69, 11. 22-24).
8. The Specification teaches that the "role of MR in angiogenesis
was investigated using the rat aortic ring assay. Segments of rat aorta were
embedded in Matrigel and treated with either antibody MR 7 or purified MR
ectodomain protein. The sprouting vessels were allowed to develop over
five day[s] before scoring by three independent observers" (Spec. 73, 1. 27 to
74, 1. 2).
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Application 11/890,213
9. The Specification teaches that "treatment of the aortic rings
with either MR 7 or MR ectodomain resulted in significant decrease in
sprouting of vessels from the aortic segment" (Spec. 74, 11. 22-24).
Principles of Law
"[A ]s long as an applicant has disclosed a 'fully characterized
antigen,' either by its structure, formula, chemical name, or physical
properties, or by depositing the protein in a public depository, the applicant
can then claim an antibody by its binding affinity to that described antigen."
Noelle v. Lederman, 355 F.3d 1343, 1349 (Fed. Cir. 2004).
However, "[ c ]laiming antibodies with specific properties, e.g., an
antibody that binds to human TNF-a with A2 specificity, can result in a
claim that does not meet written description even if the human TNF -a
protein is disclosed because antibodies with those properties have not been
adequately described." Centocor Ortho Biotech, Inc. v. Abbott
Laboratories, 636 F.3d 1341, 1352 (Fed. Cir. 2011).
Analysis
Noelle and Centocor establish two points along a continuum of
written description for antibodies. The written description issue turns on
whether the instant fact pattern fall closer to Noelle or falls closer to
Centocor. We begin by turning to the factual evidence.
The Specification evidences that the prior art and Appellants disclose
a full characterized antigen, the human magic roundabout protein (MR), also
called ECSM4 (FF 1) that was known in the prior art (FF 2) and whose
sequence was disclosed in the Specification (FF 3). The Specification
further provides a specific sequence for the lg region of the MR protein (FF
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Application 11/890,213
4). The Specification teaches the correlation between angiogenesis and
tumors and cancer (FF 5) and provides an example of an antibody to MR
including sequences for the CDR regions of the antibody (FF 6-7). The
Specification teaches that the MR antibody inhibits angiogenesis in the rat
aortic ring assay (FF 8-9).
Thus, consistent with Noelle and the USPTO written description
guidelines, Appellants have not only disclosed a fully characterized antigen
by structure and physical properties, but have also provided some
characterization of a particular antibody that binds to that antigen (FF 3, 7).
However, Centocor (and Abbvie Deutsch/and GMBH & Co., KG v.
Janssen Biotech, Inc., 759 F.3d 1285 (2014)) differentiate between antibody
claims to the entire genus of antibodies that bind an antigen and species
claims to a subset of that genus limited to antibodies that bind the antigen
but require particular properties for the antibody. See Centocor, 636 F.3d at
1352; cf Abbvie, 759 F.3d at 1301. In both Centocor andAbbvie, antibody
claims requiring specific binding specificities and affinities failed to satisfy
the written description requirement.
Claim 4 7 is drawn to the species of antibodies to MR that bind to the
lg region of the MR protein and function in angiogenesis treatment. Unlike
Centocor and Abbvie, no specific level of affinity is required for the
antibodies in claim 47. More subtly, in Centocor, the claim at issue did not
recite the specific target epitope sequence of the antigen, nor did the
Specification or prior art disclose the sequence that would function to
neutralize the antigen. Centocor, 636 F.3d at 1346. By contrast, claim 47
specifically recites a sequence for the lg region of MR, SEQ ID NO: 4 (cf
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Application 11/890,213
FF 4 ), and the Specification identifies this lg region as the binding target for
inhibition of angiogenesis (FF 5, 6, 9).
Therefore, unlike Centocor and Abbvie, the instant Specification
describes a subgenus of antibodies that function to treat tumor-associated
angiogenesis by providing a specific subportion of the MR protein that
serves as the antigen target for the subgenus of antibodies (FF 4--5), and
evidence that a specific antibody member of that subgenus targeting the lg
region of MR functioned to reduce vessel sprouting in a biological assay (FF
8-9).
We recognize, but find unpersuasive, the Examiner's finding that
"there is no described or art-recognized correlation or relationship between
the structure of the anti-MR antibodies of the method invention and the
required functions for those antibodies" (Ans. 13). At the time of invention
in 2003, the skilled artisan was easily able to generate antibodies to known
antigenic sequences without undue experimentation. With a known antigen
sequence and sufficient ready cash, anti-MR monoclonal antibodies would
have been readily available. Further, the Specification identifies the region
of the MR protein necessary to generate antibodies that inhibit angiogenesis,
the lg region, an extracellular portion of the MR protein (FF 4--5). The
Examiner provides no evidence demonstrating that monoclonal antibodies
generated against the specific lg sequence of claim 4 7 would have been
unable to treat angiogenesis.
We recognize, but find unpersuasive, the Examiner's finding that
"because angiogenesis is primarily a microvascular event and the aorta is a
macrovessel, this makes the rat aortic ring assay a less than ideal choice for
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Application 11/890,213
correlating any given anti-MR antibody (structure) effect to angiogenesis"
(Ans. 18). That the rat aortic ring assay is not the ideal choice does not
diminish the evidence presented in the Specification that the MR7 antibody,
targeting the lg region of MR, inhibits vessel sprouting (FF 8-9). The
Examiner does not rebut this evidence, nor does the Examiner rebut either
Bicknell Declaration, and present any evidence that the aortic ring assay is
unreliable.
We therefore conclude that Appellants have conveyed with reasonable
clarity to the skilled artisan that, as of the filing date, they were in possession
of the invention as demonstrated by the disclosure in the specification (FF
1-9).
Conclusion of Law
The evidence of record does not support the Examiner's position that
a tumor treatment method comprising "administering a monoclonal antibody
that selectively binds to the lg region of magic roundabout" fails to satisfy
the written description requirement
SUMMARY
In summary, we reverse the rejection of claims 47, 76, 78, and 79
under 35 U.S.C. § 112(a) or 35 U.S.C. § 112 (pre-AIA), first paragraph, as
failing to comply with the written description requirement.
REVERSED
tc
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