Ex Parte Marinkovich

Patent Trial and Appeal Board

Nov 14, 2017

12733418 (P.T.A.B. Nov. 14, 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.
12/733,418 05/20/2010 M. Peter Marinkovich STAN-577 9024
77974 7590 11/16/2017
Stanford University Office of Technology Licensing
Bozicevic, Field & Francis LLP
201 REDWOOD SHORES PARKWAY
SUITE 200
REDWOOD CITY, CA 94065
EXAMINER
ALLEN, MICHAEL D
ART UNIT PAPER NUMBER
1642
NOTIFICATION DATE DELIVERY MODE
11/16/2017 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):
docket@bozpat.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte M. PETER MARINKOVICH
Appeal 2016-004433
Application 127733,41s1
Technology Center 1600
Before DEMETRA J. MILLS, FRANCISCO C. PRATS, and
RICHARD J. SMITH, Administrative Patent Judges.
PRATS, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134(a) involves claims to a method of
treating squamous cell carcinoma. The Examiner entered three rejections for
anticipation.
We have jurisdiction under 35 U.S.C. § 6(b). We affirm one of the
rejections, but reverse the other two.
STATEMENT OF THE CASE
The Specification discloses that laminin-332 “(formerly called
laminin-5', kalinin, nicein, or BM6000) is a heterotrimeric extracellular
1 Appellant identifies The Board of Trustees of the Leland Stanford Junior
University and Department of Veterans Affairs as the real parties in interest.
Appeal Br. 1.
Appeal 2016-004433
Application 12/733,418
matrix protein that is initially synthesized and secreted in an unprocessed
form with an a3 chain of 200 kDa, a P3 chain of 140 kDA, and a y2 chain of
155 kDA.” Spec. 138.
The physiological processing of the laminin y2 chain “is described,
for example, by Amano, et al. (2000) J Biol Chem 275, 22728-22735, herein
specifically incorporated by reference for teachings of laminin processing
sites.” Id. 140.
The amino acid sequence of the laminin y2 subunit of laminin 332 is
provided as Appellant’s SEQ ID NO: 2. Id. 143.
The portion of laminin y2 removed by proteolytic processing is
composed of residues 1—434 of SEQ ID NO: 2. Id. 148 (“By ‘processed’
herein is meant that the peptide is dissociated SEQ ID NO: 2 residues 1—
434.”).
The portion of laminin y2 removed by proteolytic processing includes
domains III, IV, and V of the laminin y2 chain. See Appellant’s Fig. 6
(showing processing site within domain III, with deleted portion composed
of residues 1—434 including a portion of domain III, and domains IV and V
in their entireties).
Appellant’s invention is based on the discovery that the normally
excised portion of the laminin y2 chain is present in squamous cell
carcinoma (“SCC”) tumors, but is not present in normal skin cells. Spec.
1148 (“Using antibodies against these fragments we showed a complete
lack of staining in normal skin, but positive expression in frozen sections of
SCC tumors in two patient SCC tumors . . . .”); id. 1154 (“[EJither
truncation of the precursor domains IV—V of the laminin y2 chain or
injection of ant-y2 IV—V pAb [polyclonal antibody] resulted in a significant
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Application 12/733,418
impairment of tumor formation after 5 weeks. Each condition shown was
the average of 5 mice tested.”).
Claims 8 and 10-12 are on appeal and read as follows:
8. A method of treating squamous cell carcinoma (SCC)
in a patient comprising administering a therapeutically effective
amount of one or more antibodies in a pharmaceutically
acceptable carrier, wherein one or more of said antibodies
specifically binds to region V or region IV within laminin 332
y2 processed region IV—V polypeptide SEQ ID NO:2, residues
1— 434, and inhibiting SCC tumorigenesis.
10. The method according to Claim 8, wherein said
antibody is a polyclonal antibody.
11. The method according to Claim 8, wherein said
antibody is a monoclonal antibody.
12. The method according to Claim 8, wherein said SCC
is selected from the group consisting of skin cancer, lung
cancer, head cancer, gastric cancer, colorectal, throat cancer,
cancer of the urinary tract, cancer of the reproductive tract,
esophageal cancer, and bronchiogenic carcinoma.
Appeal Br. 16.
The following rejections are before us for review:
(1) Claims 8 and 10-12, under 35 U.S.C. § 102(b), over Findell2 (Ans.
2-3);
(2) Claim 8, 10, and 12, under 35 U.S.C. § 102(b), over Tryggvason
’6463 (Ans. 3^4); and
(3) Claims 8 and 10—12, under 35 U.S.C. § 102(e), over Tryggvason
’447 4 (Ans. 4-5).
2 US 2002/0076736 A1 (published June 20, 2002).
3 WO 96/10646 A1 (published Apr. 11, 1996).
4 US 2007/0065447 A1 (published Mar. 22, 2007).
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Application 12/733,418
STANDARD OF REVIEW
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden ... of presenting a
prima facie case of unpatentability. . . .
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of the
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.
CLAIM INTERPRETATION
As seen below, claim interpretation is central to our decision with
respect to two of the Examiner’s rejections. We, therefore, evaluate the
respective contentions on that issue before assessing the merits of the
Examiner’s rejections.
Claim 8, the sole independent claim, recites administering to a patient
an antibody that “specifically binds to region V or region IV within laminin
332 y2 processed region IV—V polypeptide SEQ ID NO:2, residues 1^434.”
Appeal Br. 16.
Appellant contends, essentially, that the claimed antibody must bind
specifically to region IV or region V within the polypeptide composed of
residues 1—434 of SEQ ID NO: 2, and that claim 8 does not encompass an
antibody that binds to other regions, such as region III, within that
polypeptide. See Appeal Br. 3—5 (citing Amano5 as evidence that it was
recognized in the art that the processing site of y2 is within region III).
5 Satoshi Amano et al., Bone Morphogenetic Protein 1 Is an Extracellular
Processing Enzyme of the Laminin 5 y2 Chain, 275 J. Biol. Chem. 22728—
22735 (2000).
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Application 12/733,418
The Examiner contends, based on Appellant’s arguments, based on
48 and 150 of the Specification, and based on Appellant’s Figure 6, that
Appellant has acted as his own lexicographer, and defined regions IV and V
of the y2 chain as the polypeptide composed of residues 1—434 of SEQ ID
NO: 2. Ans. 22—27. Therefore, the Examiner reasons, claim 8 encompasses
any antibody that binds specifically to any portion of the polypeptide
composed of residues 1—434 of SEQ ID NO: 2. Id.
We conclude that the preponderance of the evidence supports
Appellant’s position.
It is well settled that during examination, the PTO must interpret
terms in a claim using “the broadest reasonable meaning of the words in
their ordinary usage as they would be understood by one of ordinary skill in
the art, taking into account whatever enlightenment by way of definitions or
otherwise that may be afforded by the written description contained in the
applicant’s specification.” In re Morris, 127 F.3d 1048, 1054 (Fed. Cir.
1997).
When an inventor seeks to define a term in a manner inconsistent with
an ordinary artisan’s interpretation, “this must be done with reasonable
clarity, deliberateness, and precision.” In re Paulsen, 30 F.3d 1475, 1480
(Fed. Cir. 1994) (holding that specification generally describing desirable
features and capabilities of a portable computer did not establish a specific
definition for the term “computer” different from the ordinary and
accustomed meaning).
In the present case, we acknowledge the Specification’s disclosure,
identified by the Examiner, of “a truncated laminin y2 cDNA which created
a protein product lacking the first 434 residues on the N-terminus (domain
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Application 12/733,418
IV—V) proximal to where normal processing occurs.” Spec. 1150 (citation
omitted).
The Examiner does not persuade us, however, that this disclosure is
sufficiently clear, deliberate, or precise, so as to constitute a redefinition of
the art-recognized regions/domains of the y2 chain, particularly given the
Specification’s express adoption of Amano’s description of the
physiological processing of the y2 chain. See Spec. 140. Indeed, the
disclosure at 1150 is readily distinguished from the definitions expressly set
out in the Definitions section of Appellant’s Specification. Id. 20—36.
Moreover, as seen in Appellant’s Figure 6, the y2 chain processing site is
shown within region III, and the polypeptide composed of residues 1—434 of
SEQ ID NO: 2 includes a significant portion of region III.
Also, Figure 6’s disclosure of the y2 processing site as being within
region III is consistent with Amano’s disclosure that the “y chain is cleaved
within the second epidermal growth factor-like repeat of domain III.”
Amano 22728.
Figure 6’s disclosure of the cleavage site as being after residue 434,
and within region III is also consistent with Tryggvason ’447’s disclosure
that “y2 is believed to be composed of five domains corresponding
approximately to the following regions: Domain V: amino acid residues 22-
196; Domain IV: amino acid residues 197-381; Domain III: amino acid
residues 382-602; and Domain 1 & 2: amino acid residues 603-1193.”
Tryggvason ’447 13 (emphasis added).
Thus, because Appellant’s disclosure of the y2 chain processing site
as being within region III is consistent with the art of record, and because
Appellant’s Specification does not set out a specific definition modifying the
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Application 12/733,418
art-recognized boundaries of regions IV and V of the y2 chain, the Examiner
does not persuade us that Appellant has acted as his own lexicographer, such
that claim 8 encompasses any antibody that binds to any portion of the
polypeptide composed of residues 1—434 of SEQ ID NO: 2.
To the contrary, Appellant persuades us, based on the language in
claim 8, and based on an ordinary artisan’s understanding of the terminology
of laminin y2 chain processing, that under the broadest reasonable
interpretation consistent with the Specification, the claimed antibody must
bind specifically to region IV or region V within the polypeptide composed
of residues 1—434 of SEQ ID NO: 2, and that claim 8 does not encompass an
antibody that binds to only other regions, such as region III, within that
polypeptide.
ANTICIPATION—FINDELL
In asserting that Findell anticipates claims 8 and 10—12, the Examiner
finds that Findell describes using antibodies that bind to an amino acid
sequence at a cleavage site between regions III and IV of the y2 chain. Ans.
2 (“This cleavage site comprises the residues CYSG/DENP (Paragraph
0026) which correspond to amino acid residues 431—438 of Seq. ID No. 2 . .
. and so is directed to part of Laminin-5 cited residues 1—434.”).
As noted above, however, the antibody of claim 8 must bind
specifically to region IV or region V within the polypeptide composed of
residues 1—434 of SEQ ID NO: 2, and claim 8 does not encompass an
antibody that binds to only other regions, such as region III, within that
polypeptide. As noted above, moreover, Amano discloses that the y2 chain
cleavage site, to which Findell’s antibodies bind, is entirely within region
III. Amano 22728. As noted above also, Tryggvason ’447 discloses that y2
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Application 12/733,418
region III is composed of amino acid residues 382—602. Tryggvason ’447 1
3.
Thus, Appellant persuades us that the Examiner has not shown by a
preponderance of the evidence that Findell describes a method of treating
SCC that uses an antibody which binds specifically to region IV or region V
of the y2 chain, as claim 8 requires. We, therefore, reverse the Examiner’s
anticipation rejection of claim 8 and its dependent claims 10—12 over
Findell.
ANTICIPATION—TRYGGVASON ’447
In asserting that Tryggvason ’447 anticipates claims 8 and 10-12, the
Examiner finds that Tryggvason ’447 describes using an antibody that “in
particular binds between amino acids 395—414 (0304). This falls within the
region of IV—V as defined by Applicant in the instant application.'1'’ Ans. 5
(emphasis added).
As discussed above, however, the Examiner does not persuade us that
Appellant has redefined the art-recognized regions/domains of the y2 chain.
We note, moreover, that amino acids 395—414 identified by the Examiner
fall entirely within region III of y2. See Tryggvason ’447 ]f 3. We note also
that Tryggvason ’447 focuses almost entirely on targeting region III (see id.,
in particular, || 5—6), and the Examiner identifies no other portion of y2
targeted by Tryggvason ’447.
Thus, Appellant persuades us that the Examiner has not shown by a
preponderance of the evidence that Tryggvason ’447 describes a method of
treating SCC that uses an antibody which binds specifically to region IV or
region V of the y2 chain, as claim 8 requires. We, therefore, reverse the
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Application 12/733,418
Examiner’s anticipation rejection of claim 8 and its dependent claims 10—12
over Tryggvason ’447.
ANTICIPATION—TRYGGVASON ’646
The Examiner’s Prima Facie Case
In asserting that Tryggvason ’646 anticipates claims 8, 10, and 12, the
Examiner finds that claims 38 and 39 of Tryggvason ’646 “explicitly teach a
method for inhibiting the invasive growth of a malignant cell comprising
contacting to the cell a polyclonal antibody specific for laminin 5 gamma 2
protein (26).” Ans. 4.6
In that regard, the Examiner notes that “Figure 4A provides Seq ID
NO: 13 which is the full length gamma 2 chain of laminin 5. A polyclonal
antibody to this chain will have antibody specie[s] that readily bind[]
domains IV and V of laminin 5 (laminin 332) gamma 2 chain.” Id-
Analysis
In this instance, Appellant does not persuade us that the Examiner’s
prima facie case of anticipation is not supported by a preponderance of the
evidence.
Tryggvason ’646 discloses that its invention “provides for the
identification, diagnosis, monitoring, and treatment of invasive cells using
the laminin 5 gamma-2 chain protein or nucleic acid sequence, or antibodies
thereto.” Tryggvason ’646, Abstract (emphasis added).
Regarding the y2 chain, Tryggvason ’646 discloses as follows:
Kallinin/laminin 5 contains unique laminin varient [sic] chains,
one of which, the y2 chain, has recently been cloned and
6 Although the Examiner cites to “[cjlaims 38-49” (Ans. 4), Tryggvason
’646 includes only claims 1—40. Tryggvason ’646, 23—26.
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Application 12/733,418
sequenced. The y2 chain has a mass of -130 kd and is thus
smaller than the “classical” -200 kd pi and yl light chains of
laminin. The domain structure of the y2 chain also differs from
that of the yl chain in that it lacks the amino-terminal globular
domain (domain VI) believed to function in intermolecular
cross-linking of laminin molecules to form networks. In
addition, domains III, IV, and V (containing EGF-like repeats)
in y2 are shorter than in the yl chain.
Tryggvason ’646, 1 (emphasis added; citations omitted).
In its diagnostic embodiments, Tryggvason ’646 discloses hybridizing
to a target tissue a “nucleic acid sequence [which] comprises all. . . of an
open reading frame of the nucelic [sic] acid sequence for the y2 chain
(Figure 4) encoding the amino acid sequence of the y2 chain (Figure 4).” Id.
at 6.
Tryggvason ’646 discloses that its invention “also provides for the
intervemtion [sic] of y2 chain interaction with surrounding tissues by using
specific anti-y2 chain antibodies (monoclonal or polyclonal) to inhibit the y2
chain biological activity.” Id.
Tryggvason ’646 discloses that, using in situ hybridization that
employed y2 cDNA fragments, “[i]n all four squamous cell carcinomas
investigated, the same pattern of y2 chain expression was found as in other
carcinomas. The signals were found only in cancer cells, and only in areas
with signs of ongoing invasion (Figure 2, C—G).” Id. at 17.
In a “prospective example” {id. at 20), Tryggvason ’646 discloses that
“[t]o examine perturbation of the y2 protein, the tumor cells can be pre­
treated with antibodies directed to the y2 protein, to inhibit the activity of the
y2 chain protein in its functional role in tumor cell metastasis” {id. at 22).
Claim 38 of Tryggvason ’646 recites “[a] method for inhibiting the
invasive growth of a malignant cell comprising contacting to the cell an
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Application 12/733,418
effective inhibiting amount of an antibody specific for laminin y2 protein.”
Tryggvason ’646, 26.
Claim 39 of Tryggvason ’646 recites “[t]he method of Claim 38,
wherein the antibody is a polyclonal antibody.” Id.
Given the disclosures cited above, in particular the disclosure that
laminin y2 expression was found in squamous cell carcinoma (SCC) but not
normal cells, and that the invasive growth of malignant cells can be inhibited
by administering a polyclonal antibody specific for laminin y2 protein,
Appellant does not persuade us that the Examiner erred in finding that an
ordinary artisan viewing Tryggvason ’646 would have at once envisaged
administering an antibody specific for laminin y2 protein to an SCC patient,
as recited in Appellant’s claim 8.
In particular, Appellant does not persuade us that Tryggvason ’646’s
disclosure is limited to inhibiting the interactions of the fully processed y2
with a ligand or binding partner. See Appeal Br. 8—9; Reply Br. 5—6.
Appellant does not identify any specific disclosures in Tryggvason ’646
mentioning processed y2. Nor does Appellant identify any specific
disclosures in the reference suggesting that its claimed treatment method is
limited to inhibiting the interaction of processed y2 and another binding
partner.
To the contrary, Tryggvason ’646 describes the y2 protein used in its
methods as containing regions IV and V. See Tryggvason ’646, 1
(describing “domains III, IV, and V (containing EGF-like repeats) in y2”
(emphasis added)). Indeed, as noted above, Tryggvason ’646 discloses that
hybridization experiments can be performed using the entire y2 nucleic acid
sequence. Id. at 6. Given these disclosures, Appellant does not persuade us
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Application 12/733,418
that, when disclosing the administration of a y2-specific polyclonal antibody
for the inhibition of the invasive growth of malignant cells, Tryggvason ’646
would have been viewed as being limited to inhibiting the interactions of the
fully processed y2, lacking regions IV and V.
Moreover, because Tryggvason ’646 describes the y2 protein used in
its methods as containing regions IV and V (Tryggvason ’646, 1), and
describes using an antibody to that protein to inhibit invasive growth of
malignant cells (id. at 26), Appellant does not persuade us (see Appeal Br.
10) that the Examiner erred in finding that a polyclonal antibody to y2 would
include antibody species that bind specifically to those regions, as required
by Appellant’s claim 8. Nor are we persuaded that Tryggvason ’646 fails to
describe administering a therapeutically effective amount of that antibody,
given the express disclosure of using the antibody to inhibit invasive growth
of malignant cells. See Tryggvason ’646, 26.
That Tryggvason ’646 might not include a working example of such
an antibody does not persuade us that the reference fails to describe the
antibody. See Impax Labs., Inc. v. Aventis Pharms. Inc., 468 F.3d 1366,
1382 (Fed. Cir. 2006) (“[AJnticipation does not require actual performance
of suggestions in a disclosure. Rather, anticipation only requires that those
suggestions be enabled to one of skill in the art.”) (Quoting Bristol-Myers
Squibb Co. v. Ben Venue Labs., Inc., 246 F.3d 1368, 1378 (Fed. Cir. 2001)).
In the present case, Appellant advances no persuasive evidence or
reasoned argument showing that Tryggvason ’646 fails to provide an
enabling disclosure of a polyclonal antibody to the y2 protein containing
regions IV and V, or that administering that antibody would inhibit the
invasive growth of malignant cells. In that regard, we note, as Appellant
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contends (Reply Br. 7), that Amano discloses that unprocessed y2 had not
been observed in tissue extracts (Amano 22734).
As noted above, however, Tryggvason ’646 provides the full length
amino acid sequence of the y2 protein including regions IV and V
(Tryggvason ’646, Fig. 4), expressly describes the y2 protein used in its
methods as containing regions IV and V {id. at 1), and also describes using
an antibody to that protein to inhibit invasive growth of malignant cells {id.
at 26). Given these disclosures, that unprocessed y2 might not have been
observed in tissue extracts does not persuade us that an ordinary artisan
would have been unable to prepare a polyclonal antibody to the y2 protein
containing regions IV and V, or administer that antibody to inhibit the
invasive growth of malignant cells, as taught in the reference, and as recited
in Appellant’s claim 8.
In sum, for the reasons discussed, Appellant does not persuade us that
a preponderance of the evidence fails to support the Examiner’s prima facie
case that Tryggvason ’646 anticipates the process recited in Appellant’s
claim 8. We, therefore, affirm the Examiner’s anticipation rejection of that
claim over that reference. Because they were not argued separately, claims
10 and 12 fall with claim 8.
SUMMARY
For the reasons discussed, we affirm the Examiner’s rejection of
claims 8, 10, and 12, under 35 U.S.C. § 102(b), over Tryggvason ’646.
For the reasons discussed, however, we reverse the Examiner’s
rejection of claims 8 and 10—12, under 35 U.S.C. § 102(b), over Findell.
For the reasons discussed, we also reverse the Examiner’s rejection of
claims 8 and 10-12, under 35 U.S.C. § 102(e), over Tryggvason ’447.
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Application 12/733,418
TIME PERIOD
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
14