Ex Parte McIntire et al

Board of Patent Appeals and Interferences

Jun 18, 2010

10663497 (B.P.A.I. Jun. 18, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte JENNIFER JONES MCINTIRE, ROSEMARIE DEKRUYFF,
DALE T. UMETSU, and GORDON FREEMAN
__________

Appeal 2010-001105
Application 10/663,497
Technology Center 1600
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Decided: June 18, 2010
__________

Before DEMETRA J. MILLS, FRANCISCO C. PRATS,
JEFFREY N. FREDMAN, 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 lack of enablement and lack of written description. We have
jurisdiction under 35 U.S.C. § 6(b).

Appeal 2010-001105
Application 10/663,497

STATEMENT OF CASE
The following claims are representative.
1. A method of screening for a human individual's predisposition to
atopy, the method comprising:
analyzing said individual for the presence of at least one TIM-11
polymorphism by contacting a biological sample comprising DNA or
mRNA from said individual with probes that specifically bind
under stringent conditions to nucleic acid sequences of a TIM-1 gene;
wherein the presence of said polymorphism is indicative of an
individual's predisposition to develop said atopy.

4. The method according to Claim 1, wherein said analyzing step
comprises
contacting a biological sample comprising DNA or mRNA from said
individual with a probe that specifically binds to the nucleic acid sequence
ATGACAACGACTGTTCCA, SEQ ID NO:22, BASES 472-489, encoding
the amino acid sequence MTTTVP, SEQ ID NO:25, residues 158-163; and
detecting the presence of a complex formed between said probe and
said DNA or mRNA.

7. The method according to Claim 1, wherein said biological sample is blood
or a derivative thereof.

8. A method of screening for a human individual's predisposition to
atopy, the method comprising:
analyzing said individual for the presence of an INS157
polymorphism in TIM-1 by contacting a biological sample comprising DNA
or mRNA from such individual with a probe that specifically binds to the
nucleic acid sequence ATGACAACGACTGTTCCA, SEQ ID NO:22, bases
472-489, encoding the amino acid sequence MTTTVP, SEQ ID NO:25,
residues 158-163;
detecting the presence of a complex formed between said probe and
said genomic DNA, mRNA or a transcript thereof; and

1 T-cell immunoglobulin domain and mucin domain.
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analyzing said individual for the presence of hepatitis A virus (HAV)
seropositivity wherein said seropositivity in an individual comprising an
allele of TIM-I comprising the amino acid sequence MTTTVP, SEQ ID
NO:25, residues 158-163 is indicative of a reduced risk of developing atopy.

20. A method of screening for a human individual's predisposition to atopy,
the method comprising:
analyzing said individual for the presence of an INS1 57
polymorphism in TIM-1 by contacting a biological sample comprising DNA
or mRNA from said individual with a probe that specifically binds to a
nucleic acid sequence encoding the amino acid sequence MTTTVP, SEQ ID
NO:25, residues 158-163;
wherein the presence of said INS157 polymorphism is indicative of an
individual's predisposition to develop said atopy.

21. The method according to Claim 20, wherein said biological
sample is blood or a derivative thereof.

22. The method according to Claim 20, further comprising the step
of:
analyzing said individual for the presence of hepatitis A virus (HAV)
seropositivity,
wherein seropositivity in an individual expressing an allele of TIM-1
comprising the amino acid sequence MTTTVP, SEQ ID NO:25, residues
158-163 is indicative of a reduced risk of developing atopy.

23. A method of screening for a human individual's predisposition
to atopy, the method comprising:
analyzing said individual for the presence of at least one TIM-1
polymorphism in exon 3 by contacting a biological sample comprising DNA
or mRNA from said individual with probes that specifically bind under
stringent conditions to nucleic acid sequences in exon 3 of a TIM-I gene;
wherein the presence of said polymorphism is indicative of an
individual's predisposition to develop said atopy.

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Cited References
Kroese et al., Genetic tests and their evaluation: Can we answer the key
questions?, 6 GENET MED 475-480 (2004).

Jack Lucentini, Gene Association Studies Typically Wrong, 18 THE
SCIENTIST 20 (2004).

John P.A. Ioannidis,Why Most Published Research Findings are False, 2
PLOS MED e124 (2005).

Andrew T. Hattersley and Mark I. McCathy, What makes a good genetic
association study? 366 LANCET 1315-1323 (2005).

Robert A. Hegele, SNP Judgments and Freedom of Association, 22 ARTH.
THROMB. VASC. BIOL 1058-1061 (2002).

GeneCard, HAVCR1, hepatitis A virus cellular receptor, available at
www.genecards.org pp. 1-11.

Noguchi et al., Insertion/deletion coding polymorphisms in hHAVcr-1 are
not associated with atopic asthma in the Japanese population, 4 GENES AND
IMMUNITY 170-173 (2003).

Dale T. Umetsu and Rosemarie H. DeKruyff, Regulation of Tolerance in the
Respiratory Tract TIM-1, Hygiene, and the Environment, 1029 ANN. N.Y.
ACAD. SCI. 88-93 (2004).

Graves et al., Association of atopy and eczema with polymorphisms in T-cell
immunoglobulin domain and mucin domain – IL-2-inducible T-cell kinase
gene cluster in chromosome 5q33, 118 J. ALLERG. CLIN. IMMUNOL 650-656
(2005).

McIntire et al., Hepatitis A virus link to atopic disease, 425 NATURE 576
(2003).

Sizing et al., Epitope-Dependent Effect of Anti-Murine TIM-1 Monoclonal
Antibodies on T Cell Activity and Lung Immune Responses, 178 J.
IMMUNOLOGY 2249-2261 (2007).
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Chae et al., Molecular Variations in the Promoter and Coding Regions of
Human Tim-1 Gene and Their Association in Koreans With Asthma, 64
HUMAN IMMUNOLOGY 1177-1182 (2003).

Gao et al., Genetic variants of the T-cell immunoglobulin mucin 1 but not the
T-cell immunoglobulin mucin 3 gene are associated with asthma in an
African American population, 115 J. ALLERGY CLIN. IMMUNOL. 982-988
(2005).

Grounds of Rejection
1. Claims l, 4, 7-8, and 20-23 are rejected under 35 U.S.C. § 112, first
paragraph, for lack of enablement.
2. Claims 1, 4, 7, and 23 are rejected 35 U.S.C. § 112, first paragraph for
lack of written description.

Discussion
ISSUE
The Examiner concludes that
because the specification while being enabling for a method for
determining a Caucasian or Asian's predisposition to atopy[2]
protection by detecting the presence of homozygous
polymorphism of 157insMTTTVP (polymorphism 1, SEQ ID
No. 22), of TIM-1 in a hepatitis virus A positive Caucasian
individual, wherein the presence of the MTTTVP insertion is
indicative of a Caucasian's predisposition to protect against
atopy, does not reasonably provide enablement for a method for
screening for a human individual's predisposition to any atopy by
analyzing for the presence of any TIM-1 polymorphism.

(Ans. 3.)

2 Atopy is defined as asthma, allergic rhinitis and atopic dermatitis according
to the Specification, page 1.
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Appellants contend that the Specification enables claims of the
pending claim scope. Appellants contend that a description of common
polymorphisms in TIM-1 and linkage of TIM-1 locus to the development of
atopy can be found in the Specification on pages 8 and 13. (App. Br. 8.)
The issue is: Is the full scope of the claims supported by an enabling
disclosure? More particularly, does the Specification enable a method for
screening any form of atopy with any polymorphism of TIM-1, as claimed?

FINDINGS OF FACT
For a complete fact finding with respect to the lack of enablement
rejection see the Answer pages 3-14.

PRINCIPLES OF LAW
[A]s part of the quid pro quo of the patent bargain, the applicant's
specification must enable one of ordinary skill in the art to
practice the full scope of the claimed invention. That is not to say
that the specification itself must necessarily describe how to
make and use every possible variant of the claimed invention, for
the artisan's knowledge of the prior art and routine
experimentation can often fill gaps, interpolate between
embodiments, and perhaps even extrapolate beyond the disclosed
embodiments, depending upon the predictability of the art.

AK Steel Corp. v. Sollac, 344 F.3d 1234, 1244 (Fed. Cir. 2003) (citation
omitted).
Factors that should be considered in determining whether a
specification is enabling, or if it would require an undue amount of
experimentation to practice the invention include: (1) the quantity of
experimentation necessary to practice the invention, (2) the amount of
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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. See In re Wands, 858 F.2d 731, 737
(Fed. Cir. 1988).
“Enablement is determined as of the effective filing date of the patent,
In re Hogan, 559 F.2d 595, 604 (CCPA 1977).” Plant Genetic Systems, N.V.
v. DeKalb Genetics Corp., 315 F.3d 1335, 1339 (Fed. Cir. 2003). See also
Enzo Biochem Inc. v. Calgene Inc., 188 F.3d 1362, 1371 (Fed. Cir. 1999).
A claim may… encompass inoperative embodiments and still meet
the enablement requirement of 35 U.S.C. § 112, first paragraph. See Atlas
Powder Co. v. E.I. Du Pont De Nemours & Co., 750 F.2d 1569, 1576 (Fed.
Cir. 1984), In re Angstadt, 537 F.2d 498, 504 (CCPA 1976).

ANALYSIS
We agree with the Examiner’s statement of the enablement rejection
as applicable to claims 1, 4, 7, and 23 and the Examiner’s fact finding and
responses to Appellants’ argument and adopt them as our own. The
Examiner has faithfully considered the Wands factors in the enablement
analysis. We concur with these findings.
We do not find, however, that the Examiner’s evidence supports lack
of enablement of claims 8, 20, 21, and 22, particularly in view of the fact
that the Examiner has indicated that the Specification is enabling for a
method for determining a Caucasian or Asian's predisposition to atopy
protection by detecting the presence of homozygous polymorphism of
157insMTTTVP (polymorphism 1, SEQ ID No. 22), of TIM-1 in a hepatitis
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virus A positive Caucasian individual, and this is essentially the scope of
claims 8 and 22. (Spec. ¶06; Ans. 3.)3
The fact that claims 8 and 22 also encompass other ethnic groups than
Caucasian or Asian does not necessarily render these claims lacking in
enablement. A claim may encompass inoperative embodiments and still
meet the enablement requirement of 35 U.S.C. § 112, first paragraph. The
Examiner has failed to show by a preponderance of the evidence that the one
of ordinary skill in the art would have considered the majority of the claim
scope as lacking in enablement.
With claims the scope of claims 8 and 22 enabled, it follows from the
Specification and claims 8 and 22 that the presence of the INS157
polymorphism is indicative of an individual's predisposition to develop
atopy and in claims 20 and 21. We find no evidence available at the time of
filing of the present application to support lack of enablement of claims 20
and 21. The lack of enablement rejection with respect to claims 8 and 20-22
is reversed. The lack of enablement rejection of claims 1, 4, 7 and 23 is
affirmed.

Written Description
Claims 1, 4, 7, and 23 are rejected 35 U.S.C. § 112, first paragraph for
lack of written description.

3 While we understand that enablement and written description are separate
statutory requirements we find it noteworthy that the Examiner has also
considered claims 8, 20, 21, and 22 as described in the Specification as well,
and has not included them in the written description rejection.
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ISSUE
The Examiner finds that the Specification demonstrates that
Appellants were in possession of a method for determining a Caucasian or
Asian's predisposition to atopy protection by detecting the presence of
homozygous polymorphism of 157insMTTTVP (polymorphism 1, SEQ ID
No. 22), of TIM-1 in a hepatitis virus A positive Caucasian individual,
wherein the presence of the MTTTVP insertion is indicative of a Caucasian's
predisposition to protect against atopy.
Appellants contend that one of ordinary skill in the art would
recognize a reasonable correlation between atopy and members of the genus
is readily established by the disclosure of the instant application and since
every species in the genus does not have to be tested for the genus to be
enabled. (App. Br. 29.)
Issue: Does the written description support the pending claim scope?
Were Appellants in possession of the pending claim scope?

PRINCIPLES OF LAW
“The purpose of the written description requirement is to prevent an
applicant from later asserting that he invented that which he did not.” Amgen
Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1330 (Fed. Cir. 2003).
The written description requirement applies to all claims and requires
that the specification objectively demonstrate that the applicant actually
invented—was in possession of—the claimed subject matter. Ariad
Pharmaceuticals, Inc. v. Eli Lilly and Co., 598 F.3d. 1336, 1349 (Fed. Cir.
2010). “Although many original claims will satisfy the written description
requirement, certain claims may not. For example, a generic claim may
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define the boundaries of a vast genus of chemical compounds, and yet the
questions may still remain whether the specification, including the original
claim language, demonstrates that the applicant has invention species
sufficient to support a claim to the genus.” Id. at 1370-1371. A sufficient
description of a genus requires the disclosure of either a representative
number of species falling within the scope of the genus, or structural features
common to the members of the genus so that one of skill in the art can
“visualize or recognize” the members of the genus. Id. at 1350.
In analyzing whether the written description requirement is met for
genus claims, it is first determined whether a representative number of
species have been described by their complete structure. University of
California v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997).

ANALYSIS
We concur with the Examiner’s findings and conclusions with respect
to the lack of written description rejection and pages 15-18 of the Answer.
As to claim 1, the Examiner finds that the claimed invention
encompasses methods comprising the analysis and detection of
an enormous and wide variety of nucleic acid sequences. The
claims are broadly drawn to a method that encompass a plurality
of nucleic acids an extremely large genus of polymorphic
variants of the TIM-1 gene with any nucleotide content (A or G
or C or T) at any position within the TIM-1 gene. Thus the
claims encompass the detection of any of different nucleic acids
wherein the nucleic acid sequence is correlated with an
association of disease. Nucleic acids of such a large genus have
not been taught by the specification.

In analyzing whether the written description requirement is
met for genus claims, it is first determined whether a
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representative number of species have been described by their
complete structure. The instant specification provides the
sequence of SEQ ID No. 18, 20, 22, 24, 26, and 28. The
specification also provides the amino acid sequence of TIM-1 as
SEQ ID No. 19, 21, 23, 25, 27, and 29. The specification
provides analysis of the insertion of the … amino acid sequence
of MTTTVP at position 157 and indicating that this insertion is
indicative of association of disease.

(Ans. 16.)
We conclude, as did the Examiner, that the “specification does not
teach any association with any other polymorphic variation disclosed in the
specification, for example deletion 195∆Thr, 157insMTTVP, T140A,
V161A, V167I, T172A, and N258D that are indicative of association of
atopic immunological disorders.” (Id.)
To satisfy the written description requirement we determine whether a
representative number of species have been sufficiently described by other
relevant identifying characteristics (i.e. other than nucleotide sequence, gene
name, and specific polymorphic position), specific features and functional
attributes that would distinguish different members of the claimed genus. In
the present case, the Specification does not provide any characteristics that
would allow one to identify any other TIM-1 family of genes from another
organism or any other particular polymorphisms, portions or fragments or
variants of the disclosed sequence that would allow for the diagnosis of any
type of atopic immunological disorder based on detection of the non-
disclosed gene. (Ans. 16-17.)
The Specification supports that the inventor was in possession the
claimed method of screening to the extent that the insertion of the amino
acid sequence MTTTVP at position 157 and indicates that this insertion is
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indicative of association of disease and that persons with this insert, who are
hepatitis A positive have a predisposition toward protection against atopy.
We do not find the Specification provides a description of any other
polymorphism associated with atopy in a manner which evidences
possession of the genus of TIM-1 polymorphisms generally.
In sum we find no evidence of record of a representative number of
polymorphisms associated or used to determine a predisposition to atopy to
indicate that the inventor was in possession of the invention throughout the
full claim scope of claim 1.

CONCLUSION OF LAW
The enablement rejection is affirmed as to claims 1 4, 7, and 23, but
reversed as to claims 8, and 20-22. The written description rejection is
affirmed.
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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