THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY

Patent Trials and Appeals Board

Nov 13, 2020

2020001247 (P.T.A.B. Nov. 13, 2020)

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.
15/175,848 06/07/2016 Jie Liu STAN-737CON 6973
77974 7590 11/13/2020
STANFORD UNIVERSITY OFFICE OF TECHNOLOGY LICENSING
BOZICEVIC, FIELD & FRANCIS LLP
201 REDWOOD SHORES PARKWAY
SUITE 200
REDWOOD CITY, CA 94065
EXAMINER
HADDAD, MAHER M
ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
11/13/2020 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 JIE LIU, IRVING L. WEISSMAN, and RAVINDRA MAJETI
__________

Appeal 2020-0012471
Application 15/175,848
Technology Center 1600
__________

Before FRANCISCO C. PRATS, TAWEN CHANG, and
CYNTHIA M. HARDMAN, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL

Pursuant to 35 U.S.C. § 134(a), Appellant appeals from the
Examiner’s decision to reject claims 8 and 10. We have jurisdiction under
35 U.S.C. § 6(b).2
We AFFIRM.

STATEMENT OF THE CASE
“Macrophages clear pathogens and damaged or aged cells from the
blood stream via phagocytosis.” Spec. ¶ 1. “CD47 is a broadly expressed

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies the Board of Trustees of the Leland
Stanford Junior University as the real party in interest. Appeal Br. 1.
2 We heard oral argument on October 1, 2020.
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transmembrane glycoprotein” that “interacts with its receptor on
macrophages, SIRPα, to inhibit phagocytosis of normal, healthy cells.” Id.
CD47, however, “is also constitutively upregulated on a number of
cancers, including myeloid leukemias. Overexpression of CD47 on a
myeloid leukemia line increases its pathogenicity by allowing it to evade
phagocytosis.” Spec. ¶ 4.
To address the issue of overexpression of CD47 in cancer cells, “[t]he
present invention provides anti-CD47 antibodies having low
immunogenicity in humans.” Spec. ¶ 5. One of the anti-CD47 antibodies
discussed in Appellant’s Specification is designated “5F9.” Id. ¶ 107.
The 5F9 antibody appears to be a mouse antibody obtained from an
anti-CD47 hybridoma. See Spec. ¶ 107. The Specification discloses two
humanized versions of the 5F9 antibody, as well as a chimeric version of the
5F9 antibody. See id. ¶¶ 108–111 (Example 2); see also Fig. 13 (evaluating
CD47 binding of “humanized 5F9 version 1,” “humanized 5F9 version 2,”
and “chimeric 5F9”).
The Specification discloses that the two humanized versions of the
5F9 antibody, as well as the chimeric version of the 5F9 antibody, bind to
CD47 at a level comparable to that of the humanized B6H12 antibody,
another antibody known to bind to CD47. See Spec. ¶¶ 108–111 (Example
2); Fig. 13. The Specification discloses that binding of the chimeric and
humanized versions of the 5F9 antibody to CD47 blocks interaction between
CD47 and its receptor (SIRPα), thereby inducing phagocytosis in cultured
cells at a rate comparable to that of the humanized B6H12 antibody. See id.
¶ 111; Fig. 14.
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As to antibodies more generally, the Specification explains that
formation of an antibody’s antigen binding site involves coordination of six
hypervariable complementarity determining regions (CDRs), three of which
are in the variable domain of the antibody’s light chain (VL), and three of
which are in the variable domain of the antibody’s heavy chain (VH). See
Spec. ¶ 36.
The Appeal Brief explains, and the Examiner does not dispute, that
the three complementarity determining regions (CDR1, CDR2, and CDR3)
of the light chain variable domains (VL) of the 5F9 antibody have the amino
acid sequences set forth in SEQ ID NO: 23, 24, and 25, respectively. See
Appeal Br. 2 (“The sequence listing provided by applicants provides the
sequence of SEQ ID NO:23, 24 and 25, and those sequences are identified in
the sequence listing as ‘5F9 light chain CDR1’; ‘5F9 light chain CDR2’;
‘5F9 light chain CDR3’, respectively.”).
Appellant’s claims 8 and 10 are the claims on appeal, and read as
follows:
8. An immunoglobulin comprising a variable light
(VL) region containing the VL complementar[it]y regions,
CDR1, CDR2 and CDR3, respectively set forth in SEQ ID
NO:23, 24 and 25.
10. The immunoglobulin of claim 8, wherein the VL
region comprises an amino acid sequence selected from the
group consisting of the SEQ ID NO:41, SEQ ID NO: 42 and
SEQ ID NO: 43.
Appeal Br. 9.
The Appeal Brief explains, and the Examiner does not dispute, that
SEQ ID NO: 41, 42, and 43 define the complete amino acid sequence of the
variable region of the 5F9 antibody light chain, and those sequences contain
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within them the sequences in SEQ ID NO: 23, 24, and 25, respectively. See
Appeal Br. 2 (“[C]laim 8 defines specific complementary [sic] determining
regions of the immunoglobulin light chain variable region, while claim 10
defines the complete variable region sequences.”).
The sole rejection before us for review is the Examiner’s rejection of
claims 8 and 10, 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. Final Act. 2–8.3
DISCUSSION
The Dispute
The Examiner determined, based on certain USPTO training
materials, that claims reciting antibodies must “explicitly recite the binding
antigen in addition to all 6 CDR regions for fulfillment of the written
description requirements under § 112, 1.” Final Act. 2 (citing Antibody
Structure4).

3 Final Action entered September 24, 2018. The rejection in the Final
Action included claims 1–7 and 9. See Final Act. 2. Subsequent to the Final
Action, however, claims 1–7 and 9 were canceled. See Appeal Br. 9 (Claims
App’x).
4 Antibody Structure is “training material given by Bennett Celsa, Example
2: (Ab genus: modified CDR’s) slides 34-40 . . .
http://www.cabic.com/bcp/060209/BCelsa_ WDA.ppt#959,2,Antibody
Structure).” Final Act. 2.
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Based on those training materials, the Examiner determined that “a
single antibody species would not be deemed by one of skill in the art to be
representative of a claim that defines an antibody that binds antigen X
comprising at least 90% homology to the 6 CDR of the VH and VL chains.”
Final Act. 3.
Appellant contends that skilled artisans were “well-aware of the
general features of antibodies and immunoglobulins.” Appeal Br. 4 (citing
Spec. ¶¶ 35–36). Therefore, Appellant contends, because the amino acid
sequences recited in claims 8 and 10 “have been fully characterized and are
provided in full . . . the light chain sequence is fully defined, and is described
in in [sic] sufficient detail that one skilled in the art can reasonably conclude
that the inventor had possession of the claimed invention.” Id.
Appellant contends in addition that it is “well-known that heavy and
light chains freely associate. Rather, it appears that a limitation not present
in the claim (binding to CD47) is imputed to be required. As antigen-
specific binding is not required by the claim, any heavy chain could be
present.” Appeal Br. 7. Therefore, Appellant contends, claims 8 and 10 do
not “omit an element that is an essential or critical feature of the invention.
The fact that the protein sequences provided by Appellants correspond to
those of an antibody should not set up an artificial barrier to patentability
that is not required of a polypeptide other than an antibody.” Id. at 7–8.
The Examiner responds that paragraphs 35 and 36 of the Specification
support the position that the three CDR regions of both the light and heavy
chains are required for functional antigen-binding immunoglobulins. Ans. 4.
The Examiner determines, moreover, that the “broadest reasonable
interpretation of the claimed immunoglobulins include[s] antibodies
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exhibiting binding specificity to a specific antigen. Neither the
specification, nor the prior art provides any examples to support the premise
of VL CDR 1-3 of an antibody would result in antigen binding.” Id. at 5.
The Examiner cites Weiskopf5 as evidence that “both VL and VH of the 5F9
antibody are required to provide the required binding to human CD47.” Id.
Appellant replies by reiterating that “there is no requirement in the
claim, or in the definition of an immunoglobulin as known in the art or as
explicitly set forth in the specification, that a known, or that a specific,
antigen be bound by the immunoglobulin.” Reply Br. 2. In particular,
Appellant contends, “[i]t is not required that the immunoglobulin binds to
the human CD47 protein.” Id.
Appellant contends, in addition, that the Examiner “has provided no
reason to doubt that heavy and light chains of immunoglobulins can pair to
generate multitude of different combinations, and Appellants submit that one
of skill in the art reasonably expects various heavy chain sequences to stably
associate with the provided light chain sequence.” Reply Br. 3.
Analysis
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.

5 Kipp Weiskopf et al., CD47-blocking immunotherapies stimulate
macrophage-mediated destruction of small-cell lung cancer, 126 J. CLIN.
INVEST. 2610–2620 (2016).
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We select claim 8 as representative of the rejected claims. See 37
C.F.R. 41.37(c)(1)(iv). In the present case, Appellant does not persuade us
that a preponderance of the evidence fails to support the Examiner’s
determination that the subject matter of Appellant’s claim 8 lacks sufficient
descriptive support in Appellant’s Specification.
“[T]he written description requirement with respect to particularly
claimed subject matter is met if the specification shows that the stated
inventor has in fact invented what is claimed, that he had possession of it.
. . . [P]ossession is shown by disclosure in the patent.” AbbVie Deutschland
GmbH & Co. v. Janssen Biotech, Inc., 759 F.3d 1285, 1299 (Fed. Cir. 2014)
(citation omitted); see also Ariad Pharmaceuticals, Inc. v. Eli Lilly and Co.,
598 F.3d 1336, 1351 (Fed. Cir. 2010) (The test for sufficiency of the
disclosure “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.”).
“One particular question regarding the written description requirement
has been raised when a genus is claimed but the specification only describes
a part of that genus that is insufficient to constitute a description of the
genus.” AbbVie, 759 F.3d at 1299. “[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. (citations and internal quotations
omitted); see also id. at 1300 (“[A]nalogizing the genus to a plot of land, if
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the disclosed species only abide in a corner of the genus, one has not
described the genus sufficiently to show that the inventor invented, or had
possession of, the genus.”).
In the present case, Appellant’s representative claim 8 recites a genus
in the form of an “immunoglobulin” that has a variable light (VL) region
that contains the VL complementarity regions CDR1, CDR2 and CDR3, set
forth in SEQ ID NO:23, 24 and 25, respectively. Appeal Br. 9. As
Appellant contends, claim 8 does not recite that the claimed immunoglobulin
binds to any particular antigen. See id.
Appellant’s Specification discloses that the term “immunoglobulin”
encompasses antigen-binding antibodies, as well as certain
non-antigen-binding molecules:
“Antibodies” (Abs) and “immunoglobulins” (Igs) are
glycoproteins having the same structural characteristics. While
antibodies exhibit binding specificity to a specific antigen,
immunoglobulins include both antibodies and other antibody-
like molecules which lack antigen specificity. Polypeptides of
the latter kind are, for example, produced at low levels by the
lymph system and at increased levels by myelomas.
Spec. ¶ 33.
Thus, because claim 8 does not require the claimed immunoglobulin
to bind to any particular antigen, and because “immunoglobulins include . . .
antibodies” (Spec. ¶ 33), the genus recited in Appellant’s claim 8, when
viewed in light of the Specification, encompasses a first set of species:
(a) any antibody that has the three claimed CDR sequences, with no
limitation as to the antigen to which the antibody binds. When viewed in
light of the Specification, the genus recited in Appellant’s claim 8 also
encompasses a second set of species: (b) any antibody-like molecule that has
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the three claimed CDR sequences, but which lacks antigen specificity,
exemplified by polypeptides produced at low levels by the lymph system
and at increased levels by myelomas. Appellant does not persuade us that
the Specification provides adequate support for either set of species of
molecule encompassed by the genus recited in claim 8.
As to the first set of species encompassed by claim 8’s genus
(antibodies that have the three claimed CDR sequences with no limitation as
to the antigen to which the antibody binds), the only antibody species
disclosed by the Specification as having claim 8’s CDR sequences are the
5F9 antibody itself, humanized 5F9 version 1, humanized 5F9 version 2, and
the chimeric 5F9, as discussed above. See Spec. ¶¶ 107–111. Each of those
species of antibody binds specifically to CD47, and each of those species of
antibody includes not only the light chain CDR sequences recited in claim 8,
but also the heavy chain CDR sequence of the 5F9 antibody. See id. ¶ 110
(disclosing use of both 5F9 heavy and light chains to prepare CD47-binding
5F9 humanized variants).
We are not persuaded that the Specification’s disclosure of four
antibodies that bind to a single specific antigen (CD47), all of which
antibodies (as urged by the Examiner and not disputed by Appellant) require
all six of their CDR sequences to achieve that binding, is sufficient to
support the genus of antibodies encompassed by Appellant’s claim 8—
antibodies that have the claimed CDR sequences with no limitation as to the
antigen to which the antibody binds. The fact that the three light chain CDR
sequences recited in claim 8 might “freely associate” (Appeal Br. 7) with
heavy chain sequences other than the heavy chain CDR sequences of the
5F9 antibody does not negate the fact that all of the antibodies disclosed in
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the Specification as having claim 8’s CDR sequences bind to CD47, and
require a specific set of three complementary heavy chain CDR sequences
(which are not recited in claim 8) to achieve that binding.
Again, the generic term “immunoglobulin” in claim 8 “include[s] . . .
antibodies” and “antibodies exhibit binding specificity to a specific antigen.”
Spec. ¶ 33 (emphasis added). Thus, as the Examiner contends, claim 8’s
genus of immunoglobulins encompasses antibodies, which necessarily bind
to a specific antigen, but claim 8 lacks any limitation as to the antigen bound
by the claimed antibodies, and instead requires only that the claimed
antibodies have the three VL CDR sequences recited in the claim. In
contrast to the breadth of antibodies encompassed by claim 8, the only
antibodies disclosed in the Specification as having the three VL CDR
sequences in claim 8 bind specifically to a specific antigen (CD47), and also
have a specific set of three complementary VH CDR sequences required to
achieve that binding. Given these facts, we agree with the Examiner that
Appellant’s Specification fails to provide species that are sufficiently
representative of the genus of antibodies recited in Appellant’s claim 8. See
AbbVie, 759 F.3d at 1300 (“[A]nalogizing the genus to a plot of land, if the
disclosed species only abide in a corner of the genus, one has not described
the genus sufficiently to show that the inventor invented, or had possession
of, the genus.”).
We acknowledge, as Appellant contends, that claim 8 does not require
the claimed immunoglobulins to bind to a specific antigen, nor does claim 8
required the claimed immunoglobulins to bind to CD47. See Appeal Br. 7;
Reply Br. 2. As discussed above, however, the only non-antigen-binding
immunoglobulins disclosed in the Specification are “antibody-like
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molecules” such as “[p]olypeptides . . ., for example, produced at low levels
by the lymph system and at increased levels by myelomas.” Spec. ¶ 33.
Thus, as explained above, in addition to antibodies, the genus of
immunoglobulins recited in claim 8 encompasses antibody-like molecules
that have the three claimed CDR sequences, but which lack antigen
specificity, exemplified by polypeptides produced at low levels by the lymph
system and at increased levels by myelomas.
We are not persuaded that Appellant’s Specification provides
sufficient descriptive support for the claimed genus of non-antigen-binding
immunoglobulins. Other than the highly generic language in paragraph 33
stating that non-antigen-binding immunoglobulins are antibody-like
polypeptides produced at low levels by the lymph system and at increased
levels by myelomas, the Specification fails to describe the specific structure
of any particular non-antigen-binding immunoglobulin polypeptides, much
less the specific structure of a non-antigen-binding immunoglobulin
polypeptide that has all three of the CDR recited in claim 8. Nor do we
discern any persuasive evidence of record suggesting what the specific
structures of such non-antigen-binding immunoglobulin polypeptides might
be. Appellant does not persuade us, therefore, that the Specification
describes the structure of the claimed genus of non-antigen-binding
immunoglobulin polypeptides sufficiently to a skilled artisan.
Moreover, Appellant does not identify, nor do we discern, any
representative examples of non-antigen-binding immunoglobulin
polypeptides having the three CDR sequences recited in claim 8. To the
contrary, as seen in the review of the Specification above, although
paragraph 33 provides a definition of immunoglobulins that includes
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non-antigen-binding molecules, the Specification viewed as a whole
describes Appellant’s invention as anti-CD47 antibodies (or nucleic acids
encoding them), culminating in the examples of humanized anti-CD47
antibodies that include the CDR sequences recited in claim 8. See Spec. ¶ 5
(“The present invention provides anti-CD47 antibodies having low
immunogenicity in humans.”); id. ¶¶ 107–111 (Example 2).
We acknowledge that the Specification describes using
immunoglobulin elements to modify the structures of the anti-CD47
antibodies in certain instances. See, e.g., Spec. ¶ 83 (using human
immunoglobulin constant regions when humanizing mouse anti-CD47
antibodies). Appellant, however, does not identify any disclosure, in the
form of examples or otherwise, specifically suggesting that the invention
described by the Specification involves the preparation of
non-antigen-binding molecules that include any of the disclosed CDR
regions. Therefore, considering the four corners of the Specification as a
whole, we are not persuaded by Appellant’s contention that it possessed, or
even invented, non-antigen-binding molecules that include the CDR
sequences recited in claim 8.
In sum, for the reasons discussed, Appellant does not persuade us that
the Examiner erred in finding that the Specification lacks adequate
descriptive support for the antibodies encompassed by claim 8, or for the
non-antigen-binding immunoglobulins encompassed by claim 8. We
therefore affirm the Examiner’s rejection of claim 8 for failure to comply
with the written description requirement.
As to claim 10, we acknowledge Appellant’s contention that “it is
appropriate to consider the claims separately.” Appeal Br. 2. Appellant,
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however, does not advance any argument specifically directed to any
particular limitation of claim 10. Claim 10, therefore, falls with claim 8.
See 37 C.F.R. 41.37(c)(1)(iv).

DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
8, 10 112(a) or
112, first
paragraph
Lack of Written
Description
8, 10

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

AFFIRMED