Ex Parte Maeda et al

Patent Trial and Appeal Board

Jul 19, 2017

13719926 (P.T.A.B. Jul. 19, 2017)

United States Patent and Trademark Office
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O.Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
13/719,926 12/19/2012 Masatsugu Maeda 26570-0096005 / CH:NFK,
F
7308
26161 7590 07/21/2017
FISH & RICHARDSON P.C. (BO)
P.O. BOX 1022
MINNEAPOLIS, MN 55440-1022
EXAMINER
WEHBE, ANNE MARIE SABRINA
ART UNIT PAPER NUMBER
1633
NOTIFICATION DATE DELIVERY MODE
07/21/2017 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):
PATDOCTC@fr.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MASATSUGU MAEDA and NORIKO YAGUCHI1
Appeal 2017-000092
Application 13/719,926
Technology Center 1600
Before DEMETRA J. MILLS, ULRIKE W. JENKS, and RACHEL H.
TOWNSEND, Administrative Patent Judges.
MILLS, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35U.S.C. § 134. The Examiner has rejected
the claims for lack of written description and lack of enablement. The claims
are also rejected for obviousness-type double patenting. We have jurisdiction
under 35 U.S.C. § 6(b).
STATEMENT OF THE CASE
According to the Specification, the present invention relates to novel
hemopoietin receptor proteins. Spec. 1. One such protein is NR10.
NR10 is expected to be expressed in a restricted
population of cells in the hematopoietic tissues, and thus, anti-
NR10 antibodies are useful for the isolation of such cell
1 According to Appellants, Chugai Seiyaku Kabushiki Kaisha is the real
party in interest. See Br. 1.
Appeal 2017-000092
Application 13/719,926
populations. The isolated cell populations may be used in cell
transplantation. Furthermore, it is expected that the anti-NRIO
antibody may be used for the diagnosis or treatment of diseases,
such as leukemia.
Spec. 9. The pending claims include antibodies to NR10 and modified and/or
mutant NR10 polypeptides.
The following claim is representative.
15. An antibody or an antigen-binding fragment thereof
that binds specifically to a polypeptide of any one of (a) to (g)
below:
(a) a polypeptide comprising the amino acid sequence of
any one of SEQ ID Nos: 2, 4 or 17;
(b) a polypeptide encoded by a nucleic acid comprising a
coding region in the nucleotide sequence of any one of SEQ ID
NOs: 1, 3 or 16;
(c) a polypeptide that comprises the amino acid sequence
of any one of SEQ ID NOs: 2, 4 or 17, in which 2 to 30 amino
acids are replaced, deleted, inserted and/or added and that is
functionally equivalent to the protein comprising the amino acid
sequence of any one of SEQ ID NOs: 2, 4 or 17;
(d) a polypeptide encoded by a nucleic acid that hybridizes
under low-stringent conditions of 42°C, 2x SSC, and 0.1% SDS
with the nucleic acid comprising the nucleotide sequence of any
one of SEQ ID NOs: 1, 3 or 16, and that encodes a protein
functionally equivalent to the protein comprising the amino acid
sequence of any one of SEQ ID NOs: 2, 4 or 17;
(e) a polypeptide consisting of the amino acid sequence
from Ala at position 33 to Glu at position 238 in the amino acid
sequence set forth in SEQ ID NO: 2;
(f) a polypeptide consisting of the amino acid sequence
from Ala at position 33 to Val at position 252 in the amino acid
sequence set forth in SEQ ID NO: 4; and
(g) a polypeptide consisting of the amino acid sequence
from Ala at position 33 to lie at position 662 in the amino acid
sequence set forth in SEQ ID NO: 17.
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Application 13/719,926
Cited References
Maeda US 8,017,738 B2 Sept. 13,2011
Paula J. Waters, Degradation of Mutant Proteins, Underlying “Loss
of Function ” Phenotypes, Plays a Major Role in Genetic Disease, 3
Curr. Issues Mol. Biol. 57-65 (2001) (“Waters”).
Igor Zhukov et al., Conservative mutation Met8 —> Leu affects the
folding process and structural stability of squash trypsin inhibitor
CMTI-I, Protein Science 273-79 (2000) (“Zhukov”).
Grounds of Rejection
1. Claims 15—18 and 20-25 are rejected 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.
2. Claims 15—18 and 20-25 are rejected under 35 U.S.C. § 112(a)
or 35 U.S.C. § 112 (pre-AIA), first paragraph, because the Specification,
while being enabling for an antibody or antibody or antigen-binding fragment
thereof that binds specifically to a polypeptide as set forth in elements (a)-(b)
or (e)-(g) of claim 15, does not reasonably provide enablement for the scope
of antibodies which bind to the scope of polypeptides encompassed by
elements (c) or (d) of claim 15.
3. Claims 15—18 and 20-25 are rejected on the ground of
nonstatutory double patenting as being unpatentable over claims 1—21 of
Maeda (hereafter referred to as the ’738 patent).
FINDINGS OF FACT
The Examiner’s findings of fact are set forth in the Examiner’s
Answer at pages 2—19.
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Application 13/719,926
PRINCIPLES OF LAW
In making our determination, we apply the preponderance of the
evidence standard. See, e.g., Ethicon, Inc. v. Quigg, 849 F.2d 1422, 1427
(Fed. Cir. 1988) (explaining the general evidentiary standard for proceedings
before the Office).
The purpose of the written description requirement is to “ensure that
the scope of the right to exclude, as set forth in the claims, does not
overreach the scope of the inventor’s contribution to the field of art as
described in the patent specification.” Reiffin v. Microsoft Corp., 214 F.3d
1342, 1345 (Fed. Cir. 2000). To that end, to satisfy the written description
requirement, the inventor “must convey with reasonable clarity to those
skilled in the art that, as of the filing date sought, he or she was in possession
of the invention.” Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563—64
(Fed. Cir. 1991). “One shows that one is ‘in possession’ of the invention by
describing the invention, with all its claimed limitations.” Lockwood v. Am.
Airlines, 107 F.3d 1565, 1572 (Fed. Cir. 1997) (internal citation omitted)
(emphases in original).
The “written description” requirement. . . serves both to satisfy
the inventor’s obligation to disclose the technologic knowledge
upon which the patent is based, and to demonstrate that the
patentee was in possession of the invention that is claimed. . . .
The descriptive text needed to meet these requirements varies
with the nature and scope of the invention at issue, and with the
scientific and technologic knowledge already in existence.
Capon v. Eshhar, 418 F.3d 1349, 1357 (Fed. Cir. 2005).
Where claims are directed to a genus of products, the genus is
described
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Application 13/719,926
by disclosing: (1) a representative number of species in that
genus; or (2) its “relevant identifying characteristics,” such as
“complete or partial structure, other physical and/or chemical
properties, functional characteristics when coupled with a
known or disclosed correlation between function and structure,
or some combination of such characteristics.”
In re Alonso, 545 F.3d 1015, 1019 (Fed. Cir. 2008) (quoting Enzo Biochem,
Inc. v. GenProbe Inc., 323 F.3d 956, 964 (Fed. Cir. 2002) (en banc). Thus,
for example, where one “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, claiming
antibodies to an antigen from a different species based on, for example,
binding affinity, does not satisfy the function—structure correlation test and is
an improper “attempt[] to define an unknown by its binding affinity to
another unknown.” Id. Thus, the Noelle court held that a description of a
mouse antigen was not sufficient to support a claim to antibodies to a human
antigen where there was not disclosed structural elements of the human
antibody. Id. at 1348-49.
Moreover, a claim to a genus of antibodies without reciting a specific
source of antigen to which the genus of antibodies must bind may not be
fully described even where the description provides the structure of an
antigen that might serve to raise an antibody within the genus because
“‘there may be unpredictability in the results obtained from species other
than those specifically enumerated.’ Noelle v. Lederman, 355 F.3d 1343,
1350 (Fed. Cir. 2004).” Alonso. 545 F.3d at 1020. It is for this reason that
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Application 13/719,926
the Noelle court held that a description of a mouse antigen was not sufficient
to support a claim to a genus of antibodies to an antigen generic as to source.
Noelle, 355 F.3d at 1348, 1350.
The criteria for enablement, while related to written description, is,
nevertheless, a separate requirement. See, e.g., University of Rochester v. GD
Searle & Co., Inc., 358 F.3d 916, 921 (Fed. Cir. 2004). Thus, “an invention
may be enabled even though it has not been described.” Id.
The enablement requirement is often more indulgent than the
written description requirement. The specification need not
explicitly teach those in the art to make and use the invention;
the requirement is satisfied if, given what they already know, the
specification teaches those in the art enough that they can make
and use the invention without “undue experimentation.”
Amgen Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1334 (Fed. Cir.
2003) (internal citations omitted). However, “the specification must teach
those of skill in the art ‘how to make and how to use the invention as
broadly as it is claimed’.” In re Goodman, 11 F.3d 1046, 1050 (Fed. Cir.
1993). Furthermore, when considering the enablement of a genus of
products in an unpredictable art, one must keep in mind that “the required
level of disclosure will be greater than, for example, the disclosure of an
invention involving a ‘predictable’ factor such as a mechanical or electrical
element.” In re Vaeck, 947 F. 2d 488, 496 (Fed. Cir. 1991).
Rejection 1—Written description
The Examiner finds that, “[t]he claim(s) contains subject matter which
was not described in the specification in such a way as to reasonably convey
to one skilled in the relevant art that the inventor or a joint inventor, or for
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Application 13/719,926
pre-AIA the inventor(s), at the time the application was filed, had possession
of the claimed invention.” Ans. 2.
In particular, the Examiner finds that
Claim 15... recites an antibody or an antigen-binding fragment
thereof that binds specifically to a polypeptide of any one of (a)
to (g), where (c) is a polypeptide that comprises the amino acid
sequence of any one of SEQ ID NOS: 2, 4, or 17, in which 2-30
amino acids are replaced, deleted, inserted, and/or added and that
is functionally equivalent to the protein comprising the amino
acid sequence of any one of SEQ ID NOS: 2, 4, or 17, and where
(d) is a polypeptide encoded by a nucleic acid that hybridizes
under low-stringent conditions of 42°C, 2x SSC, and 0.1% SDS
with the nucleic acid comprising the nucleotide sequence of any
one of SEQ ID NOS: 1, 3, or 16, and that encodes a protein
functionally equivalent to the protein comprising the amino acid
sequence of any one of SEQ ID NOS: 2, 4, or 17.
Ans. 2—3. The Examiner also finds that the claims read on antibodies that
bind to an enormous number of mutant NR10 proteins which are
“functionally equivalent” to the wild type polypeptides set forth in SEQ
ID NOS: 2, 4, or 17. Ans. 3. In addition, the Examiner finds that the
“low-stringency hybridization [(claim element d)] also encompasses a large
number of nucleotide sequences, since low-stringency hybridization
identifies sequences with lower sequence homology than high stringency
hybridization, thus encompassing a far larger genus of nucleotides and thus
polypeptides and antibodies that bind to the polypeptides.” Ans. 3.
Appellants contend that, based on the indicated disclosures in the
Specification (Br. 3), that “[o]ne of ordinary skill in the art would have
understood that a protein with a small number of alterations (such as those as
defined in the amended claim 15 (c) and (d)) compared with the native
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Application 13/719,926
protein generally exhibits substantially the same function as the native
protein.” Br. 3.
ANALYSIS
Appellants do not argue individual claims separately in the Brief,
therefore, we select claim 15 as the representative claim. We agree with the
Examiner’s fact finding, statement of the rejection and responses to
Appellants’ arguments as set forth in the Answer. We find that the
Examiner has provided evidence to support a prima facie case of lack of
written description. We provide the following additional comment to the
Examiner’s argument set forth in the Final Office Action and Answer.
We agree with the Examiner that
the specification fails to provide an adequate description of the
genus of polypeptides encompassed by either element (c) or (d)
and thus fails to adequately describe the genus of antibodies as
claimed in claim 15 such that it is clear that appellant was in
possession of the invention as claimed at the time of filing. The
as filed specification fails to describe any polypeptides which
meet that limitations of elements (c) or (d) of claim 15, other than
the specific embodiments set forth in elements (a)-(b), and (e)-
(g)-
Ans. 3. We further agree with the Examiner that
while the specification predicts from a comparison of the
sequences of these putative proteins to database sequences that
the NR10 proteins are hemopoietin receptors, and identifies by
sequence comparison a putative ligand binding domain in the
region of Cys 43- Cys 53, the specification provides no guidance
as to the characteristics of or identi[t]y of any ligand that binds
to any one of these NR10 proteins. The specification is further
silent as [to] any actual functional characteristics of any NR10
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Application 13/719,926
protein, and is likewise silent as to the physical, chemical,
structural, and functional properties of any putative NR10 ligand.
It is further noted that while generally suggesting the
introduction of mutations in the form of amino acid substitutions,
additions, and deletions to the sequence of SEQ ID NOS: 2, 4,
and 17, the specification does not disclose any actual mutant
proteins derived from the amino acid sequences set forth in SEQ
ID NOS: 2, 4, or 17, or demonstrate that any mutant or divergent
polypeptide sequence related to SEQ ID NOS: 2, 4, or 17 shares
any functional characteristics with these sequences. Finally, the
specification is silent as to any functional assay that can be used
to identify a polypeptide which diverges from the sequence of
SEQ ID NOS: 2, 4, or 17 and which is “functionally equivalent”.
Ans 4. For the reasons presented by the Examiner in the Answer, we are not
persuaded that Appellants’ claims encompass antibodies to a small number
of polypeptide alterations, or that the Specification fully describes the
claimed genus of antibodies to functional polypeptides within the scope of
the pending claims.2
To satisfy the written description requirement, the inventor “must
convey with reasonable clarity to those skilled in the art that, as of the filing
date sought, he or she was in possession of the invention.” Vas-Cath, 935
F.2d at 1563—64. “One shows that one is ‘in possession’ of the invention by
describing the invention, with all its claimed limitations.” Lockwood, 107
F.3d at 1572.
In the present case, we do not find that Appellants have conveyed
with reasonable clarity to those skilled in the art that, as of the filing date
sought, they were in possession of either antibodies to a genus of
2 Compare, Written Description Training Materials and Guidelines, Revision
1, March 2008, Example 14.
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Application 13/719,926
polypeptides including: (c) a polypeptide that comprises the amino acid
sequence of any one of SEQ ID NOs: 2, 4, or 17, in which 2 to 30 amino
acids are replaced, deleted, inserted, and/or added and that is functionally
equivalent to the protein comprising the amino acid sequence of any one of
SEQ ID NOs: 2, 4, or 17; or (d) a polypeptide encoded by a nucleic acid that
hybridizes under low-stringent conditions of 42°C, 2x SSC, and 0.1 % SDS
with the nucleic acid comprising the nucleotide sequence of any one of SEQ
ID NOs: 1, 3, or 16, and that encodes a protein functionally equivalent to the
protein comprising the amino acid sequence of any one of SEQ ID NOs: 2,
4, or 17. Appellants have not provided a representative number of
functional antigen species to which the claimed antibody or antigen-binding
fragment must bind or a structure-function correlation of the antigen species.
In short, the antigen species recited in the claims are unknown. Moreover,
Appellants have not pointed to any known structure for the claimed
antibodies (see, e.g., Br. 3), and thus, there is no structure to which
Appellants may correlate the function of the claimed antibodies based on the
antibody alone. Thus, regarding the genus of antibodies or antigen-binding
fragments that are required to bind specifically to the unknown antigens, we
conclude Appellants’ are improperly “attempting to define an unknown by
its binding affinity to another unknown.”
The lack of written description rejection is affirmed for the reasons of
record.
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Application 13/719,926
Rejection 2— Scope of enablement
Claims 15—18 and 20-25 are rejected under 35 U.S.C. § 112(a) or 35
U.S.C. § 112 (pre-AIA), first paragraph, because the Specification, while
being enabling for an antibody or antibody or antigen-binding fragment
thereof that binds specifically to a polypeptide as set forth in elements (a)-
(b) or (e)-(g) of claim 15, does not reasonably provide enablement for the
scope of antibodies which bind to the scope of polypeptides encompassed by
elements (c) or (d) of claim 15. The Specification does not enable any
person skilled in the art to which it pertains, or with which it is most nearly
connected, to make or use the invention commensurate in scope with these
claims. Ans. 6.
The Examiner finds that
The claims as written read on antibodies which bind to an
enormous number of mutant NR10 proteins which are
“functionally equivalent” to the wild type polypeptides set forth
in SEQ ID NOS: 2, 4, or 17. SEQ ID NO: 2 is 652 amino acids
in length, SEQ ID NO: 4 is 252 amino acids in length, and SEQ
ID NO: 17 is 662 amino acids in length. Numerically, the number
of potential mutants for each sequence where between 2-30
amino acids are replaced, inserted, deleted, or added is extremely
large. Further, low-stringency hybridization also encompasses a
large number of nucleotide sequences, since low-stringency
hybridization identifies sequences with lower sequence
homology than high stringency hybridization, thus
encompassing a far larger genus of nucleotides and thus
polypeptides and antibodies that bind to the polypeptides.
However, the specification fails to provide an enabling
disclosure for the genus of polypeptides encompassed by either
element (c) or (d) and thus fails to provide an enabling disclosure
for the genus of antibodies as claimed in claim 15. The as filed
specification fails to describe any polypeptides which meet that
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Application 13/719,926
limitations of elements (c) or (d) of claim 15, other than the
specific embodiments set forth in elements (a)-(b), and (e)-(g).
Ans. 6—7.
Appellants contend that, based on specific disclosure in the
Specification mentioned in the Brief on page 4,
one of skill in the art would have known how to make the
polypeptides of categories (c) and (d) of presently amended
claim 15. Further, Appellant notes that the claim 15 is drawn to
antibodies, not the antigen to which the antibodies bind. Methods
of making antibodies were well known in the art at the priority
date. It would have been routine to generate antibodies across the
full scope of claim 15.
Id.
ANALYSIS
Appellants do not argue individual claims separately in the Brief,
therefore, we select claim 15 as representative claim. We agree with the
Examiner’s fact finding, statement of the rejection and responses to
Appellants’ arguments as set forth in the Answer. We find that the
Examiner has provided evidence to support a prima facie case of lack of
enablement throughout the claim scope. We provide the following
additional comment to the Examiner’s argument set forth in the Final Office
Action and Answer.
Appellants argue that methods of making antibodies were well known
in the art at the priority date and that it would have been routine to generate
antibodies across the full scope of claim 15. Br. 4. However, the Appellants
fail to indicate where the Specification enables one of ordinary skill in the
art to know which mutated or modified NR10 polypeptides or which NR10
mutations maintain the NR10 hemopoietin receptor protein function. In
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Application 13/719,926
other words, the, “[t]he [Specification fails to provide an enabling
disclosure for making any mutant NR10 protein which is ‘functionally
equivalent’ to an NR10 protein set forth in SEQ ID NOS: 2, 4, or 17” within
the full scope of claim 15. Ans. 8. Furthermore, “the [Specification is
silent as to any functional assay that can be used to identify a polypeptide
which diverges from the sequence of SEQ ID NOS: 2, 4, or 17 and which is
‘functionally equivalent’.” Ans. 8. In addition, Appellants admit in the
Brief that the “disclosure [in the Specification] indicates that numerous
hemopoietin receptors were known in the art and that the structural
conservation in the cytoplasmic domains of such receptors is not high.” Br.
3, emphasis added. While there are several known conserved regions in
hemopoietin receptors (Br. 3), Appellants indicate that, overall, structural
conservation in the cytoplasmic domains of such receptors is not high.
Thus, one of ordinary skill in the art reading the Specification would not
specifically be enabled to produce functional, mutated, NR10 hemopoietin
receptor.
The Examiner cites Waters and Shukov teaching unpredictability in
the art leading to undue experimentation on the part of one of ordinary skill
in the art. In particular, Waters
teaches that mutations in protein which affect protein stability,
folding, and function as associated with numerous diseases and that
while many disease associated mutations involve major deletions,
insertions, rearrangements, nonsense, or ffameshift mutations, half of
the disease associated loss of function mutations are in fact missense
mutations causing substitution of a single amino acid, and others
represent only small in frame deletions or insertions.
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Ans. 16. See also, further discussion of Waters, Ans. P. 17. “Zhukov et al.
shows that even with extensive knowledge of a wild type protein’s structure,
a single conservative amino acid substitution can have unexpected effects
(Zhukov et al., page 274).” Ans. 17. Appellants provide no rebuttal
argument to the citations of Waters and Zhukov, and the level of
unpredictability in the art leading to undue experimentation on the part of
one of ordinary skill in the art in determining which NR10 mutations
produce functional mutants. Ans. 18.
The lack of enablement throughout the claim scope rejection is
affirmed for the reasons of record.
Obviousness-type Double Patenting
Appellants do not contest the obviousness-type double patenting
rejection on the merits in the Brief. The obviousness-type double patenting
rejection is summarily affirmed.
CONCLUSION OF LAW
The cited references support the Examiner’s lack of written
description and lack of enablement throughout the claim scope rejections,
which are affirmed for the reasons of record. The obviousness-type double
patenting rejection is also affirmed. All pending, rejected claims fall.
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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