Ex Parte Norin

Board of Patent Appeals and Interferences

Jun 15, 2010

09896908 (B.P.A.I. Jun. 15, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte ALLEN J. NORIN
__________

Appeal 2009-010366
Application 09/896,908
Technology Center 1600
__________

Decided: June 15, 2010
__________

Before DONALD E. ADAMS, LORA M. GREEN, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL

This is an appeal under 35 U.S.C. § 134 involving claims to an
isolated and purified cell surface protein p38.5. We have jurisdiction under
35 U.S.C. § 6(b). We affirm.

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Statement of the Case
The Claims
Claims 41-48 are on appeal. Claim 41 is representative and reads as
follows:
1. An isolated and purified cell surface protein p38.5
having a molecular weight of about 38.5 kD which binds
natural killer cells and which is characteristically expressed
by tumor cells susceptible to cell mediated lysis by naïve
natural killer cells wherein the protein comprises an amino
acid sequence defined by SEQ. ID No. 7 or a homologue
thereof wherein up to 10% of the amino acids in SEQ. ID.
No: 7 are substituted with equivalent amino acids.

The prior art

The Examiner relies on the following prior art references to
show unpatentability:
Voet, D. and J.G., BIOCHEMISTRY 126-128, 228-234
(1990).
Mikayama et al., Molecular cloning and functional
expression of a cDNA encoding glycosylation-inhibiting
factor, 90 PROC. NATL. ACAD. SCI. USA 10056-10060
(1993).
Ngo et al., Computational Complexity, Protein
Structure Prediction, and the Levinthal Paradox in THE
PROTEIN FOLDING PROBLEM AND TERTIARY STRUCTURE
PREDICTION 491-495 (K. Merz, Jr. and S. Le Grand, Eds.,
1994).
Norin et al., A 38.5KD tumor protein is a unique
recognition structure for naive human NK cells, J. CELL
BIOCHEM. SUPPL. 123 (1993), Abstract only.
Tao et al., Molecular cloning of p38.5-K562 tumor
membrane protein: A specific ligand for human natural
killer (NK) cells, 37 AM. ASSN CANCER RES. ANN. 458,
Abstract Only #3124.
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The issues
A. The Examiner rejected claims 41-48 under 35 U.S.C. § 112, first
paragraph as not enabling for “a homologue” of the protein of SEQ ID NO:
2 (Ans. 3-5).
B. The Examiner rejected claims 41-48 under 35 U.S.C. § 112, first
paragraph as failing to satisfy the written description requirement (Ans. 5-6).
C. The Examiner rejected claim 48 under 35 U.S.C. § 112, first
paragraph, new matter for a protein “wherein the tumor is benign” (Ans. 6).
D. The Examiner rejected claims 41-48 under 35 U.S.C. § 112, first
paragraph, new matter for failure to support “equivalent amino acids”
language in the claims (Ans. 6-7).
E. The Examiner rejected claims 41-48 under 35 U.S.C. § 102(b) as
anticipated by Norin (Ans. 7).
F. The Examiner rejected claims 41-48 under 35 U.S.C. § 102(b) as
anticipated by Tao (Ans. 7-8).
G. The Examiner rejected claims 41-48 under 35 U.S.C. § 112, second
paragraph as indefinite (Ans. 8).

A. 35 U.S.C. § 112, first paragraph, Enablement
The Examiner finds that the evidence of record serves “to demonstrate
that predicting the function of protein ‘homologues’ acting as receptors or
ligands is highly uncertain and would require undue experimentation” (Ans.
4-5).
Appellant argues that “the examiner’s argument ignores the functional
limitation set forth in Claim 41 . . . the claimed homologues include not only
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structural limitation of having 90% homology to SEQ ID NO. 7, but also
include the functional limitations of binding natural killer cells” (App. Br.
8). Appellant argues that “[c]ourts have held that claims to homologues are
enabled when they include a high percentage of homology and a requirement
for a specified activity” (App. Br. 9).
Appellant argues that “the homologues of Claim 41 are further
defined by the limitation, ‘up to 10% of the amino acids in SEQ. ID NO. 7
are substituted with equivalent amino acids.’ (emphasis supplied) Since SEQ
ID NO. 7 is an 11-mer peptide, this limitation means that there would
essentially be only one substitution in the sequence” (App. Br. 9).
Appellant also cites to the Board’s decision in Ex parte Bandman,
arguing that “as in Ex Parte Bandman, the process of natural selection will
have determined the appropriate amino acid sequences in a particular allele”
(App. Br. 10-11).
In view of these conflicting positions, we frame the enablement issue
before us as follows:
Does the evidence of record support the Examiner’s conclusion that
undue experimentation would have been required to perform the method of
Claim 41?
Findings of Fact (FF)
Breadth of Claims
1. The Specification teaches that “the term ‘p38.5’ includes the
natural and recombinant proteins of 361 amino acids . . . as well as
homologs and functional fragments thereof. Functional fragments of p38.5
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may be any fragment that retains a functional activity of the 361 amino acid
protein” (Spec. 20, ll. 3-7).
2. Claim 41 is drawn to a p38.5 protein (see FF 1), with the
functional capacity to bind natural killer cells and the structural requirement
for the 10 of the 11 amino acids of SEQ ID NO: 7 (see Claim 41; Spec. 49,
ll. 2-3).
Presence of Working Examples
3. The Specification teaches in Example 8, that “a single band of
38.5 kD (p38.5) was detected from NK cell adsorbed preparations but was
not observed in T lymphocyte adsorbed preparations” (Spec. 47, l. 28 to 48,
l. 2).
4. The Specification teaches cloning a specific p38.5 sequence in
Example 20 (Spec. 55-56).
Amount of Direction or Guidance Presented
5. The Specification teaches that “[s]ubstantially homologous
p38.5 sequences have at least 90% identity” (Spec. 21, ll. 8-9).
6. The Specification teaches that “[a]ny substitutions, additions,
and/or deletions in p38.5 may be made provided that the sub[s]titution,
addition or deletion mutant of p38.5 continues to satisfy the functional
criteria, such as antigenic, immunological or NK cell-binding criteria
described herein” (Spec. 21, ll. 20-22).
7. The Specification teaches that:
it is possible to substitute amino acids in a sequence in
a peptide or a protein such as the p38.5 with equivalent
amino acids. Groups of amino acids known normally to be
equivalent are:
(a) Ala (A), Ser (S), Thr (T), Pro (P), Gly (G);
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(b) Asn (N), Asp (D), Glu (E), Gln (Q);
(c) His (H), Arg (R), Lys (K);
(d) Met (M), Leu (L), Ile (I), Val (V); and
(e) Phe (F), Tyr (Y), Trp (W)

(Spec. 21, ll. 12-19).
State of the Prior Art and Unpredictability of the Art
8. Mikayama teaches that “the possibility cannot be excluded that
a single amino acid difference between GIF and MIF may account for their
biologic activities” (Mikayama 10060, col. 2).
9. Voet teaches, regarding sickle cell anemia, that the “disease
was shown to arise from a specific amino acid change in a protein. This
mutation causes HbS to aggregate into filaments of sufficient size and
stiffness to deform erythrocytes” (Voet 127, col. 1).
10. Ngo teaches that it “is not known whether there exists an
efficient algorithm for predicting the structure of a given protein from its
amino acid sequence alone. Decades of research have failed to produce such
an algorithm” (Ngo 492).
11. The Examiner finds that “[r]egarding the benign tumors of
Claim 48 expressing the 38.5 kD surface protein of Claim 41, the
specification fails to disclose any such tumors” (Ans. 5).
Quantity of Experimentation
12. The Examiner finds that the “combined references serve to
demonstrate that predicting the function of protein ‘homologues’ acting as
receptors or ligands is highly uncertain” (Ans. 4-5).

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Skill in the Art
13. The Examiner makes no finding regarding the skill level in the
art.
Principles of Law
When rejecting a claim under the enablement
requirement of section 112, the PTO bears an initial burden
of setting forth a reasonable explanation as to why it
believes that the scope of protection provided by that claim
is not adequately enabled by the description of the invention
provided in the specification of the application.

In re Wright, 999 F.2d 1557, 1561-62 (Fed. Cir. 1993). “[T]he question of
undue experimentation is a matter of degree. The fact that some
experimentation is necessary does not preclude enablement; what is required
is that the amount of experimentation ‘must not be unduly extensive.’” PPG
Indus., Inc. v. Guardian Indus. Corp., 75 F.3d 1558, 1564 (Fed. Cir. 1996).
Factors to be considered in determining whether a disclosure
would require undue experimentation … include (1) the
quantity of experimentation necessary, (2) the amount of
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.

In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988).

Analysis
We agree with the Examiner that the Specification does not provide
sufficient guidance to enable practice of the full scope of the claimed
invention without undue experimentation. The nature of the invention
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places it in the class of invention which the Federal Circuit has characterized
as “the unpredictable arts such as chemistry and biology.” Mycogen Plant
Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
The Specification expressly defines p38.5 as encompassing “natural
and recombinant proteins of 361 amino acids . . . as well as homologs and
functional fragments thereof. Functional fragments of p38.5 may be any
fragment that retains a functional activity of the 361 amino acid protein”
(Spec. 20, ll. 3-7; FF 1).
While there are working examples of single specific mouse and
human p38.5 sequences in the Specification (see Spec. 14, Table 3), the
Specification does not teach any particular functional domains of the p38.5
protein, nor does the Specification delineate any mode of identifying such
functional domains other than by trial and error (see FF 5-7).
The prior art demonstrates that protein structure is unpredictable (FF
8-10). This directly supports the “how to make” enablement issue since
without any disclosure of functional regions of p38.5, it remains
unpredictable which “homologs” and “functional fragments” of the p38.5
protein would retain any functional activity.
Appellant argues that “the examiner’s argument ignores the functional
limitation set forth in Claim 41 . . . the claimed homologues include not only
structural limitation of having 90% homology to SEQ ID NO. 7, but also
include the functional limitations of binding natural killer cells” (App. Br.
8). Appellant argues that “[c]ourts have held that claims to homologues are
enabled when they include a high percentage of homology and a requirement
for a specified activity” (App. Br. 9).
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We are not persuaded. The instant claims do not require a “high
percentage of homology”. Unlike the claims in Novozymes, a district court
decision, which claims required 95% homology to the entire protein (see
Novozymes A/S v. Genecor Intern., Inc., 446 F.supp.2d 297, 306 (D.Del.
2006)), the instant claims, read in light of the Specification’s definition of
p.38.5 (see FF 1), encompass any homologs or functional fragments of the
361 amino acid protein, other than the 11 amino acids represented by SEQ
ID NO: 7, which may be modified by only a single amino acid change.
Thus, 350 amino acids of the 361 amino acids may be deleted or modified
without any restriction based on sequence or structure. The instant claim
does not impose any sequence requirement on 350 of the 361 amino acids of
p38.5. In Novozymes, the court noted that the Examiner had rejected claims
with 80% homology, narrower than the instant claims, only allowing those
with 95% homology. Id. at 307.
The instant facts are much closer to Amgen, where the claims were
drawn to “a polypeptide having an amino acid sequence sufficiently
duplicative of that of erythropoietin” to retain the biological function of
erythropoietin. Amgen, Inc., v. Chugai Pharmaceutical Co., Ltd., 927 F.2d
1200, 1204 (Fed. Cir. 1991). The Court found that a disclosure of a few
analogs “represents inadequate support for Amgen’s desire to claim all EPO
gene analogs.” Id. at 1213. In the instant case, there is not even a disclosure
in the Specification of a single analog of p38.5 which differs in sequence but
retains the functional elements required by the claims.
Similarly, Appellant’s citation of Ex Parte Bandman, 2005 WL
4773698 (BPAI 2005) also represents a very different situation, where the
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claim required 95% identity to the entire protein. Appellant’s claim does not
require 95% identity, nor does Appellant’s claim require that the sequence
be “naturally occurring”, instead teaching that “the term ‘p38.5’ includes the
natural and recombinant proteins of 361 amino acids . . . as well as
homologs and functional fragments thereof. Functional fragments of p38.5
may be any fragment that retains a functional activity of the 361 amino acid
protein” (Spec. 20, ll. 3-7; FF 1). Thus, Appellant’s claim encompasses any
recombinant homolog or functional fragment of p38.5 without regard to
percent identity (other than for the 11 amino acids of SEQ ID NO: 7) or
whether the sequence is naturally occurring. We agree with the Examiner
that Specification does not reasonably provide enablement for homologs or
functional fragments, in the absence of any disclosure of structure function
relationships or examples of functional homologs or fragments and in view
of the extremely broad claim (FF 1-12).
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that undue
experimentation would have been required to perform the method of Claim
41.
B. 35 U.S.C. § 112, first paragraph, written description
The Examiner finds that “[t]here is insufficient written description to
show that Applicant was in possession of any homologues of SEQ ID
NOS:2 or 7” (Ans. 5). The Examiner finds that:
As a homologue could include essentially any protein or
peptide with virtually any and all insertions, substitutions,
and deletions, one of skill in the art would conclude that the
specification fails to disclose a representative number of
species to describe the claimed genus.
Deleted: T
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(Ans. 5-6).
Appellant argues that the “homologues claimed in Claim 41 are
defined in two ways. First, Claim 41 sets forth a structural limitation of the
homologues, i.e., ‘wherein up to 10% of the amino acids in SEQ ID NO. 7
are substituted with equivalent amino acids.’” (App. Br. 11). Appellant also
argues that “Claim 41 includes a functional limitation, i.e., the homologue
must bind natural killer cells. Thus, the homologues in Claim 41 are defined
both structurally and functionally” (App. Br. 11). Appellant argues that,
based on the Written Description Guidelines, the “protein claimed in Claim
41 is defined both structurally and functionally, and therefore satisfies the
enablement requirements of § 112” (App. Br. 12).
In view of these conflicting positions, we frame the written
description issue before us as follows:
Does the evidence of record support the Examiner’s conclusion that
the disclosure of the Specification failed to demonstrate possession and
descriptive support for Claim 41?
Principles of Law
[T]he hallmark of written description is disclosure.… [T]he
test requires an objective inquiry into the four corners of the
specification from the perspective of a person of ordinary
skill in the art. Based on that inquiry, the specification must
describe an invention understandable to that skilled artisan
and show that the inventor actually invented the invention
claimed.

Ariad Pharmaceuticals, Inc. v. Eli Lilly and Co., 598 F.3d 1336, 1351 (Fed.
Cir. 2010).
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It is the Examiner's “initial burden [to] present [ ] evidence or reasons
why persons skilled in the art would not recognize in the disclosure a
description of the invention defined by the claims.” In re Wertheim, 541
F.2d 257, 263 (CCPA 1976).
Analysis
We agree with the Examiner that the Specification does not
adequately describe the claimed p38.5 protein as broadly claimed.
It is well settled that
the inventor cannot lay claim to that subject matter unless he
can provide a description of the compound sufficient to
distinguish infringing compounds from non-infringing
compounds, or infringing methods from non-infringing
methods. As the district court observed, “[t]he claimed
method depends upon finding a compound that selectively
inhibits PGHS-2 activity. Without such a compound, it is
impossible to practice the claimed method of treatment.”

University of Rochester v. G.D. Searle & Co., 358 F.3d 916, 926 (Fed. Cir.
2004).
Claim 41, as interpreted in light of the Specification, is broadly drawn
to not only to a p38.5 protein comprising SEQ ID NO: 2, or comprising the
11 amino acids of SEQ ID NO: 7, but expressly “includes the natural and
recombinant proteins of 361 amino acids . . . as well as homologs and
functional fragments thereof. Functional fragments of p38.5 may be any
fragment that retains a functional activity of the 361 amino acid protein”
(Spec. 20, ll. 3-7; FF 1). The Specification therefore must adequately
describe that genus of compounds.
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The written description requirement can be met by disclosing
“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.” Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 964,
(Fed. Cir. 2002).
In this case, the Specification references a complete sequence of p38.5
(see FF 3). However, the Specification does not describe any of the specific
structural features of p38.5 which give rise to the function of NK binding (or
indeed, to any other function). In fact, the Specification fails to identify
which region, or regions, within the 261 amino acid p38.5 protein is
involved in NK binding.
The present case is therefore analogous to Rochester. In Rochester,
the patent claimed a method of selectively inhibiting the enzyme PGHS-2
(also known as COX-2) by “administering a non-steroidal compound that
selectively inhibits activity of the PGHS-2 gene product to a human.”
Rochester, 358 F.3d at 918. The patent “describes in detail how to make
cells that express either COX-1 or COX-2, but not both …, as well as
‘assays for screening compounds, including peptides, polynucleotides, and
small organic molecules to identify those that inhibit the expression or
activity of the PGHS-2 gene product.”’ Rochester, 358 F.3d at 927.
The court held that even if a DNA sequence might support a claim to
hybridizing nucleic acids, the “same is not necessarily true in the chemical
arts more generally. Even with the three-dimensional structures of enzymes
such as COX-1 and COX-2 in hand, it may even now not be within the
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ordinary skill in the art to predict what compounds might bind to and inhibit
them.” Rochester, 358 F.3d at 925.
The concern is even more acute in the current case, where unlike in
Rochester, where the claims involved only the use of the natural COX-2
molecule, here the claims encompass any protein that is 90% similar to the
261 amino acid p38.5 protein.
Appellant has not provided any identification of a single region or
multiple regions within the p38.5 protein which are involved in NK binding.
Appellants have not provided any identification of critical residues in the
p38.5 protein which are essential to NK binding.
As in Rochester, the present application discloses the assay for
screening p38.5 and NK interaction but fails to provide p38.5 regions other
than the wild type which bind to wild type NK.
As the district court pointed out: Tellingly, … what
plaintiff's experts' [sic] do not say is that one of skill in the
art would, from reading the patent, understand what
compound or compounds-which, as the patent makes clear,
are necessary to practice the claimed method-would be
suitable, nor would one know how to find such a compound
except through trial and error …. Plaintiff's experts opine
that a person of ordinary skill in the art would understand
from reading the ′850 patent what method is claimed, but it
is clear from reading the patent that one critical aspect of the
method-a compound that selectively inhibits PGHS-2
activity-was hypothetical, for it is clear that the inventors
had neither possession nor knowledge of such a compound.

Rochester, 358 F.3d at 925-926.
Just as in Rochester, it is hypothetical which amino acid modifications
of p38.5 will share the claimed activity of binding to NK cells. In the
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Specification, there is no possession or knowledge of any such specific
compound which will form the claimed complex.
Appellant argues that, based on the Written Description Guidelines,
the “protein claimed in Claim 41 is defined both structurally and
functionally, and therefore satisfies the enablement requirements of § 112”
(App. Br. 12).
We note that the revised Written Description guidelines have changed
the analysis from that discussed by Appellant (see App. Br. 10). The March
2008 revision discusses the situation where 95% variants of a protein with
function are claimed,
[t]here is no teaching in the specification regarding which
5% of the structure can be varied while retaining the ability
of the protein to catalyze the reaction A->B. Further, there is
no art-recognized correlation between any structure (other
than SEQ ID NO: 3) and the activity of catalyzing A->B,
based on which those of ordinary skill in the art could
predict which amino acids can vary from SEQ ID NO: 3
without losing the catalytic activity. Consequently, there is
no information about which amino acids can vary from SEQ
ID NO: 3 in the claimed genus of proteins and still retain the
catalytic activity.

(Written Description guidelines at 35, in Example 10 (available at http://
www.uspto.gov/web/menu/written.pdf). The revised Written Description
guidelines conclude that the claim fails to comply with the written
description requirement because of the absence of information correlating
any structure with function. We think that this applies directly to the current
situation, where the no p38.5 structure which correlates with the NK binding
activity is disclosed and consequently, there is no information about which
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amino acids can vary and still retain the ability for the protein complex
required by claim 41.
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that the
disclosure of the Specification failed to demonstrate possession and
descriptive support for Claim 41.
C. 35 U.S.C. § 112, first paragraph, New Matter, Claim 48
The Examiner finds that the “specification and the claims as originally
filed do not provide support for the invention as now claimed, specifically, a
protein according to Claim 41 wherein the tumor is benign (now non-
malignant)” (Ans. 6).
Appellant replies that “Applicant intends to cancel Claim 48, which is
not being appealed herein” (App. Br. 14).
Accordingly, since Appellant does not contest the merits of the
rejection, we summarily affirm this rejection.
D. 35 U.S.C. § 112, first paragraph, New Matter
The Examiner finds that the “specification and the claims as originally
filed do not provide support for the invention as now claimed, specifically, a
homologue wherein up to 10% of the amino acids in SEO[sic SEQ]. ID. No:
2 or 7 are substituted with equivalent amino acids” (Ans. 6-7).
Appellant argues that the “specification describes the structure of the
homologues. On page 21 of the specification, second paragraph, applicant
discloses that a determination of whether two amino acids sequences are
substantially homologous may be based on FASTA searches as known by
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those skilled in the art” (App. Br. 12). Appellant argues that the
“specification also describes the function of the homologues” (App. Br. 13).
In view of these conflicting positions, we frame the new matter issue
before us as follows:
Does the evidence of record support the Examiner's conclusion that
Claim 41 fails to comply with the written description requirement as
incorporating new matter?
Principles of Law
It is the Examiner's “initial burden [to] present [] evidence or reasons
why persons skilled in the art would not recognize in the disclosure a
description of the invention defined by the claims.” In re Wertheim, 541
F.2d 257, 263 (CCPA 1976).
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. American Airlines, Inc., 107 F.3d 1565,
1572 (Fed. Cir. 1997).
Analysis
The amended limitation at issue is the clause in Claim 41 which states
“wherein up to 10% of the amino acids in SEQ ID No: 7 are substituted with
equivalent amino acids” (Claim 41). The Examiner argues that the
“specification simply does not disclose the claimed homologues being
substituted with ‘equivalent amino acids’” (Ans. 10).
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We are not persuaded. The Specification provides express descriptive
support for substitutions with equivalent amino acids, noting that “it is
possible to substitute amino acids in a sequence in a peptide or a protein
such as the p38.5 with equivalent amino acids” (Spec. 21, ll. 12-13; FF 7).
The Specification teaches that “[a]ny substitutions, additions, and/or
deletions in p38.5 may be made provided that the sub[s]tituion, addition or
deletion mutant of p38.5 continues to satisfy the functional criteria, such as
antigenic, immunological or NK cell-binding criteria described herein”
(Spec. 21, ll. 20-22; FF 6). The Specification also teaches that
“[s]ubstantially homologous p38.5 sequences have at least 90% identity”
(Spec. 21, ll. 8-9; FF 5).
Conclusion of Law
The evidence of record does not support the Examiner's conclusion
that Claim 41 fails to comply with the written description requirement as
incorporating new matter.
E. 35 U.S.C. § 102(b) over Norin
The Examiner finds that “Norin et al. teaches a cell surface p38.5
protein having a molecular weight of about 38.5 kD which preferentially
binds natural killer (NK) cells and which is characteristically expressed by
tumor cells susceptible to cell-mediated lysis by naive NK cells. Said p38.5
protein binds a 70 kD (p70) NK cell surface protein from humans” (Ans. 7).
Appellant argues that “neither of the cited abstracts provide the amino
acid sequence of p38.5” (App. Br. 15). Appellant argues that “the abstracts
do not describe the conditions necessary for identifying and isolating the
p38.5 protein, and the conditions necessary for determining the molecular
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weight of the p38.5 protein, and the conditions necessary to detect binding
of the isolated protein to the NK cells” (App. Br. 15). Appellant argues that
“the abstracts would not permit one skilled in the art to isolate and purify the
claimed protein without undue experimentation” (App. Br. 15).
In view of these conflicting positions, we frame the anticipation issue
before us as follows:
Does the evidence of record support the Examiner’s conclusion that
the p38.5 protein of Norin inherently anticipates the p38.5 protein of Claim
41?
Findings of Fact
14. Norin teaches identification of “a unique tumor membrane
protein(s) (TMP) that binds to NK cell surface receptor(s).” (Norin abstract).
15. Norin teaches that “biotin-labelled solubilized TMP from K562
cells were reacted with viable lymphocytes” (Norin abstract).
16. The Specification teaches that “[s]olubilized membrane proteins
from surface biotin-labeled K562 cells were reacted with immunomagnetic
bead enriched freshly isolated naïve NK cells or T lymphocytes” (Spec. 47).
17. Norin teaches that “[o]f approximately 20 adsorbed K562
proteins, a 38.5KD band bound specifically to NK cells whereas a 46KD
protein bound specifically to T-cells” (Norin abstract).
18. Norin teaches that “K562 38.5 KD protein was purified to
apparent hom[o]geneity by preparative PAGE and further studied in
functional and binding assays” (Norin abstract).
19. Norin teaches that the “purified 38.5 KD protein bound
exclusively to NK cells compared to T cells” (Norin abstract).
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20. Norin teaches that “the soluble 38.5KD K562 protein inhibited
NK cell mediated cytotoxicity in a concentration dependent manner” (Norin
abstract).
21. The Specification teaches that “p38.5 may be isolated from
cells, cell lysates, membranes or solubilized fractions or other cell
components by standard methods” (Spec. 20, ll. 15-16).
22. The Specification teaches that “purified p38.5 may be obtained
by separating the protein on preparative SDS-PAGE gels, slicing out the
band of interest and electroeluting the protein from the polyacrylamide
matrix by methods known in the art” (Spec. 20, ll. 21-23).
Principles of Law
“It is well settled that a prior art reference may anticipate when the
claim limitations not expressly found in that reference are nonetheless
inherent in it.” In re Cruciferous Sprout Litigation, 301 F.3d 1343, 1349
(Fed. Cir. 2002). See, e.g., MEHL/Biophile Int'l Corp. v. Milgraum, 192
F.3d 1362, 1365 (Fed.Cir.1999) (“Under the principles of inherency, if the
prior art necessarily functions in accordance with, or includes, the claimed
limitations, it anticipates.”)
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
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possess the characteristics of his claimed product.”). See also In re Spada,
911 F.2d 705, 708-09 (Fed. Cir. 1990).
Analysis
Norin satisfies all of the elements of Claim 41 identified by Appellant
(see App. Br. 3-4) other than identifying the sequence of the p38.5 protein.
Regarding Elements 1 and 2, Norin teaches that the protein was 38.5 kD and
was purified to homogeneity (FF 18). Regarding Element 3, Norin teaches
that the protein binds natural killer (NK) cells and is expressed by K562
cells, the identical cells used in the Specification (FF 14-17).
The Examiner has reasonably established a case of anticipation,
shifting the burden to the Appellant to demonstrate that the p38.5 protein
purified to homogeneity by Norin which binds to NK cells does not
comprise the 10 of the 11 amino acids of SEQ ID NO: 7 sequence
requirement of Claim 41. Best, 562 F.2d at 1255.
Appellant argues that “neither of the cited abstracts provide the amino
acid sequence of p38.5” (App. Br. 15).
We are not persuaded. This is the point of the inherency rejection.
The Examiner has provided significant evidence and reasoning which
support the conclusion that the p38.5 protein of Norin is identical to the
p38.5 protein being claimed. Consequently, under Best, the burden of
proving that Norin’s p38.5 protein does not inherently satisfy the sequence
requirement of Claim 41 is properly placed on Appellant. See 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
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prove that the prior art products do not necessarily or inherently possess the
characteristics of his claimed product.”).
Appellant has not provided any evidence to rebut the Examiner’s
conclusion. In this case, where Appellant appears to be the author of the
Norin paper, Appellant is reasonably best placed to provide rebuttal
evidence, if any exists.
Appellant cites a Declaration by Dr. Sitkovsky that “one skilled in the
art would not likely even attempt to isolate the protein based on the
information disclosed in the cited abstracts” (App. Br. 15).
This argument is misplaced, because Norin is not cited for
“attempting” to isolate the protein, but rather for successfully isolating the
protein (FF 18). It is this successful purification of a p38.5 protein from the
same source, K562 cells, with the same binding affinity as the protein
claimed by Appellant, which makes Norin an anticipatory reference to Claim
41.
Further, Dr. Sitkovsky’s arguments regarding Norin’s p38.5 protein
represents speculation without specific evidence. That is, when Dr.
Sitkovsky states that “[t]here are 276 human membrane proteins that fall
within 10% of the apparent molecular weight of 38,500 daltons” (Sitkovsky
Dec. ¶ 13), this statement may be true, but does not address the specific
protein of Norin which is the subject of the rejection.
When Dr. Sitkovsky continues and states that “[s]ome of these
proteins are expressed by tumor cells, and bind to a protein having a
molecular weight of about 70,000 daltons on NK cells” (Sitkovsky Dec. ¶
13), this statement is entirely without evidentiary support. Dr. Sitkovsky
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provides no evidence that 38.5 kD proteins isolated from K562 cells
routinely bind to 70 kD proteins on NK cells, but do not bind T cells.
The key issue is not whether other proteins of about 38.5 kD exist in
human cells, but whether the p38.5 protein isolated by Norin, which shares
not only the size and source of Appellant’s claimed protein, but also the
function of binding NK cells and not T cells, inherently anticipates.
Dr. Sitkovsky also states that “[i]t is my opinion that the Norin et al.
abstract and the Tao et al. abstract do not contain sufficient details to allow
scientists experienced in the field of membrane protein biochemistry (protein
scientist) to isolate and purify the protein” (Sitkovsky Dec. ¶ 4).
We are not persuaded. Appellant’s own Specification recognizes that
protein purification may occur by standard methods (FF 21). In particular,
the Specification teaches purification of the protein using preparative SDS-
PAGE gels (FF 22), the precise method used by Norin (FF 18). Finally,
Norin actually purifies the protein, a point which is unrebutted (FF 18). We
therefore find that the evidence does not support Dr. Sitkovsky’s conclusion
of non-enablement of Norin.
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that the
p38.5 protein of Norin inherently anticipates the p38.5 protein of Claim 41.
F. 35 U.S.C. § 102(b) over Tao
As we are affirming the 35 U.S.C. § 102 (b) rejection over Norin,
which covers all of the claims on the same reasoning as Tao, we vacate the
35 U.S.C. § 102(b) rejection over Tao.

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G. 35 U.S.C. § 112, second paragraph
The Examiner finds that “it is unclear precisely what is encompassed
by the term ‘equivalent amino acids’. The term is not defined in the
specification (note: the disclosure of ‘Groups of amino acids known
normally to be equivalent ...’ does not comprise a definition)” (Ans. 8).
Appellant argues that “on page 21 of the specification, applicant
specifically discloses which groups of amino acids are known normally to be
equivalent to each other” (App. Br. 19). Appellant argues that “following
the list of equivalent amino acids on page 21 of the specification, applicant
states, ‘Any substitutions, additions, and/or deletions in p38.5 may be made
provided that the substitution, addition or deletion mutant of p38.5 continues
to satisfy the functional criteria, such as antigenic, immunological or NK
cell-binding criteria described herein’” (App. Br 19).
In view of these conflicting positions, we frame the indefiniteness
issue before us as follows:
Does the evidence of record support the Examiner’s conclusion that
the phrase “equivalent amino acids” is indefinite?
Principles of Law
The test for definiteness under 35 U.S.C. § 112, second paragraph, is
whether “those skilled in the art would understand what is claimed when the
claim is read in light of the specification.” Orthokinetics, Inc. v. Safety
Travel Chairs, Inc., 806 F.2d 1565, 1576 (Fed. Cir. 1986) (citations
omitted).
In Miyazaki, the Board stated that
rather than requiring that the claims are insolubly
ambiguous, we hold that if a claim is amenable to two or
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more plausible claim constructions, the USPTO is justified
in requiring the applicant to more precisely define the metes
and bounds of the claimed invention by holding the claim
unpatentable under 35 U.S.C. § 112, second paragraph, as
indefinite.

Ex Parte Miyazaki, 89 USPQ2d 1207, 1211 (BPAI 2008).
Analysis
We find that the Appellant has the better position. As Appellant
notes, page 21 of the Specification provides an express definition of
“equivalent amino acids” (see FF 6). Even under the Miyazaki standard, the
claims are amenable to only a single plausible claim construction, in which
“equivalent amino acids” are understood in light of the Specification at page
21. Thus, for example, the Specification would permit the substitution of
phenylalanine with tyrosine or tryptophan as equivalent, but not alanine,
since it is not listed as equivalent to phenylalanine (see Spec. 21). This is
entirely definite.
Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
that the phrase “equivalent amino acids” is indefinite.
SUMMARY
In summary, we affirm the rejection of:
• claim 41 under 35 U.S.C. § 112, first paragraph as not enabling for “a
homologue” of the protein of SEQ ID NO: 2. Pursuant to 37 C.F.R. §
41.37(c)(1)(vii)(2006), we also affirm the rejection of claims 42-48, as
these claims were not argued separately.
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• claim 41 under 35 U.S.C. § 112, first paragraph as failing to satisfy
the written description requirement. Pursuant to 37 C.F.R. §
41.37(c)(1)(vii)(2006), we also affirm the rejection of claims 42-48, as
these claims were not argued separately.
• claim 48 under 35 U.S.C. § 112, first paragraph, new matter for a
protein “wherein the tumor is benign”.
• claim 41 under 35 U.S.C. § 102(b) as anticipated by Norin. Pursuant
to 37 C.F.R. § 41.37(c)(1)(vii)(2006), we also affirm the rejection of
claims 42-48, as these claims were not argued separately.

We reverse the rejection of:
• claims 41-48 under 35 U.S.C. § 112, first paragraph, new matter for
failure to support “equivalent amino acids” language in the claims.
• claims 41-48 under 35 U.S.C. § 112, second paragraph as indefinite.

We vacate the rejection of claims 41-48 under 35 U.S.C. § 102(b) as
anticipated by Tao.

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No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1)(iv)(2006).

AFFIRMED

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