Ex Parte Comb et al

Patent Trials and Appeals Board

Jun 11, 2019

15011913 - (D) (P.T.A.B. Jun. 11, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
15/011,913 02/01/2016 Michael Comb
20306 7590 06/11/2019
MCDONNELL BOEHNEN HULBERT & BERGHOFF LLP
300 S. WACKER DRIVE
32NDFLOOR
CHICAGO, IL 60606
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
CST-313 DIV 3947
EXAMINER
ROARK, JESSICA HOPE
ART UNIT PAPER NUMBER
1643
MAIL DATE DELIVERY MODE
06/11/2019 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MICHAEL COMB, AILAN GUO, JOHN EDWARD RUSH II,
JUN-MING CAI, JING LI, and JING ZHOU 1
Appeal 2018-008356
Application 15/011,913
Technology Center 1600
Before DEMETRA J. MILLS, ERIC B. GRIMES, and
RICHARD M. LEBOVITZ, Administrative Patent Judges.
GRIMES, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to an
antibody, which have been rejected for obviousness and obviousness-type
double patenting. We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
STATEMENT OF THE CASE
The Specification discloses "motif-specific, context-independent
antibodies." Spec. ,-J 2. The Specification states:
"motif-specific, context-independent antibody" means an
antibody which preferentially recognizes a plurality of peptides
1 Appellants identify the Real Party in Interest as Cell Signaling Technology,
Inc. Appeal Br. 1.
Appeal 2018-008356
Application 15/011,913
or proteins within a genome that contain the motif for which the
antibody is specific; the specificity of the antibody is thus
substantially independent of the surrounding protein or peptide
context in which the antigenic motif occurs.
Id. iJ 76.
One embodiment "provides a motif-specific, context-independent
antibody that specifically binds a recurring, modified motif consisting of
(i) at least one sumoylated lysine residue, and (ii) one or more degenerate
amino acids bound by a peptide bond to said sumoylated lysine residue." Id.
,i 21. As used in the Specification, "'degenerate amino acids' means amino
acid positions that are non-fixed and thus variant." Id. ,i 71. "[B]y
'sumoylated lysine' is meant a lysine residue attached via its epsilon amine
to a C-terminal G of the fragment ... TGG (C-terminal) of a SUMO family
member, such as Sumo-1, Sumo-2, or Sumo-3." Id. ,i 249.
"Small ubiquitin-related modifier proteins ( for Small Ubiquitin-like
Modifiers) are members of the ubiquitin-like protein family." Id. ,i 247. "In
human[s], there are three SUMO isoforms, namely[ ]SUM0-1, -2 and -3.
The covalent attachment of a SUMO protein ... (SUMOylation) to target
proteins is analogous to ubiquitination." Id.
Claims 1-8, 19, and 20 are on appeal. Claim 1 is illustrative and reads
as follows:
1. A motif-specific, context-independent antibody that
specifically binds a recurring, modified motif consisting of (i)
at least one sumoylated lysine residue, and (ii) one or more
degenerate amino acids bound by a peptide bond to said
sumoylated lysine residue.
2
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Application 15/011,913
The claims stand rejected as follows:
Claims 1-8, 19, and 20 under 35 U.S.C. § 103(a) as obvious based on
Dasso2 and Comb '1403 (Ans. 3);
Claims 1-8, 19, and 20 for obviousness-type double patenting based
on claims 1-5 of Comb '140 in view of Dasso (Ans. 11);
Claims 1-8, 19, and 20 for obviousness-type double patenting based
on claims 1-9 of Comb '0224 in view of Dasso (Ans. 12); and
Claims 1-8, 19, and 20 for obviousness-type double patenting based
on claims 1-3 of Comb '7145 in view of Dasso (Ans. 13).
I
The Examiner has rejected all of the claims on appeal as obvious
based on Dasso and Comb '140. The Examiner finds that "Dasso teaches
antibodies that specifically recognize SUMO-conjugated proteins." Ans. 4.
The Examiner also finds that "Dasso teaches that certain disease states are
associated with SUMO conjugation, and that a need exists for methods to
identify, quantitate, and localize conjugates of SUMO proteins to their target
proteins." Id. (emphasis omitted). The Examiner finds, however, that "Dasso
does not teach antibodies that bind a SUMO motif in a plurality of proteins
or a method that produces such antibodies. Instead, Dasso' s methods result
in antibodies that are specific for each particular conjugate of SUMO with a
particular protein." Id. at 5.
2 WO 2004/063214 A2, published July 29, 2004.
3 US 6,441,140 Bl, issued August 27, 2002.
4 US 7,259,022 B2, issued August 21, 2007.
5 US 7,344,714 B2, issued March 18, 2008.
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Application 15/011,913
The Examiner finds that Comb '140 "teaches a library-based method
that can be applied generally to produce antibodies that bind a ... modified
amino acid in a 'context-independent' manner." Id. The Examiner finds that
"Comb notes that the same technique can be applied to produce antibodies
that bind amino acids modified in other ways, including ubiquitination." Id.
The Examiner concludes that, because "Comb provides a broadly
applicable method and Dasso identifies the need for antibodies that
recognize SUMOylated proteins," "one of ordinary skill in the art would
have utilized the method of Comb to prepare a library of antigens to isolate
antibodies that bound a lysine modified with an addition that is a carboxy
terminal fragment of SUMO." Id. at 6 ( emphasis omitted).
We agree with the Examiner that the cited references support a prima
facie case of obviousness. Dasso teaches that "[t]he small ubiquitin-related
modifiers (SUMO) proteins ... are a group of proteins within the larger
family ofubiquitin-like proteins. The SUMO proteins, like ubiquitin ... are
covalently attached to target proteins." Dasso 1: 16-19. "The functional
significance of SUMO modification is less well characterized than is that of
ubiquitin." Id. at 2:5-6. Dasso teaches that certain diseases, in particular
acute promyelocytic leukemia, may be linked to SUMO conjugation. Id. at
2:14-17.
Dasso states that
[a] need exists for methods to identify, quantitate, and localize
conjugates of SUMO proteins to their target proteins. Tools are
needed that will assist in the study of the biological role of
particular SUMO proteins. Methods to diagnose disease states
linked to a rise or fall in the amount of a SUMO protein
conjugate or linked to a particular localization of a SUMO
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protein conjugate are also needed. Further, methods are needed
to assay for effector molecules that inhibit or activate
conjugation of a particular SUMO protein or all SUMO
proteins, or otherwise alter the amount of a SUMO protein
conjugate in a cell.
Id. at 2: 18-25.
Dasso discloses that "branched peptides of 11 residues or more
spanning the branch points of SUMO protein-target protein conjugates can
be used to generate antibodies that specifically recognize the SUMO protein-
target protein conjugates, i.e., that recognize the conjugates and do not
recognize the unconjugated SUMO protein or unconjugated target protein."
Id. at 2:28-32. "In the branched peptide, the first peptide fragment is
covalently linked to the second peptide fragment by an isopeptide bond
between the a-carboxy of the carboxy terminal glycine of the first peptide
fragment and the side chain E-amine of one of the at least one lysine residues
of the second peptide fragment." Id. at 3: 9-13.
Comb '140 discloses
a method of producing antibodies that selectively recognize
specified short amino acid motifs independent of the
surrounding amino acid, peptide, or protein sequences. The
method allows the production of antibodies that recognize
modified single amino acids, for example ... acetylated lysine,
as well other unmodified or modified motifs of one or more
amino acids.
Comb '140 at 3:35-42.
Comb '140 states that its "motif-specific, context-independent
antibodies are produced" using "a highly degenerate peptide library. In one
preferred embodiment, the library comprises XXXXXXJ*XXXXXXC
where X =all 20 amino acids except cysteine and J*=a modified (*) amino
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acid (J), for example, phosphothreonine (T*) or acetylated-lysine (K *)."
Id. at 5:30-31, 36-40. Comb '140 states that "[t]he incorporation of
modified amino acids at fixed positions should not be limited to
phosphorylation or acetylations as other modified protected amino acids can
also be incorporated, for example, amino acids modified with ... amino
acids such as ubiquitin." Id. at 5:59-66. Comb '140 provides a working
example in which "[ a ]ntibodies specifically reactive against acetylated
lysine but not reactive against non-acetylated lysine were obtained" using
the disclosed method. Id. at 16: 15-67.
We agree with the Examiner's conclusion that a person of ordinary
skill in the art would have found it obvious to use the method disclosed by
Comb '140 to raise motif-specific, context-independent antibodies specific
for a sumoylated lysine residue. Dasso teaches antibodies specific for
SUMO protein/target protein conjugates. Dasso raises its antibodies using a
branched peptide consisting of a first (SUMO protein-derived) peptide and a
second (target protein-derived) peptide; the peptides are attached via a bond
between the C-terminal glycine of the first peptide and the E-amine of a
lysine of the second peptide. Dasso 3:9-13.
Comb ' 140 teaches a general method of making antibodies that bind
to a modified amino acid regardless of the amino acids surrounding it (i.e.,
motif-specific, context-independent antibodies). It would have been obvious
to use the method taught by Comb '140 to raise antibodies specific to a
sumoylated lysine residue because Dasso teaches that research tools are
needed to study SUMO protein/target protein conjugates (Dasso 2: 18-25)
and, in particular, "[ m Jethods to diagnose disease states linked to a rise or
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fall in the amount of a SUMO protein conjugate or linked to a particular
localization of a SUMO protein conjugate are also needed." Id. at 2:20-23.
Comb '140 teaches that its method is generally applicable, and
expressly suggests applying its method to raise motif-specific, context-
independent antibodies to acetylated lysine and to amino acids modified
with ubiquitin. Comb' 140 at 5:33-40, 59-66. SUMO proteins "are a group
of proteins within the larger family ofubiquitin-like proteins." Dasso 1:16-
19. Therefore, a person of ordinary skill in the art would have had a
reasonable expectation of success in applying the method of Comb '140 to
raise motif-specific, context-independent antibodies to lysine modified with
one of the small ubiquitin-related modifier (SUMO) proteins described by
Dasso.
Appellants argue that "Dasso does not express a need or desire for
motif-specific context-independent antibodies that can bind specifically to
sumoylated proteins .... Dasso provides no wish or desire for context-
independent antibodies that can bind to sumoylated proteins." Appeal Br. 4.
Whether a person of ordinary skill in the art would have had a reason
to combine the teachings of different references, however, does not depend
on an express suggestion in one of the references. See KSR Int 'l Co. v.
Teleflex Inc., 550 U.S. 398,418 (2007): "Often, it will be necessary ... to
look to interrelated teachings of multiple patents ... in order to determine
whether there was an apparent reason to combine the known elements in the
fashion claimed by the patent at issue." See also id. at 417: "[I]f a technique
has been used to improve one device, and a person of ordinary skill in the art
would recognize that it would improve similar devices in the same way,
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using the technique is obvious unless its actual application is beyond his or
her skill." Here, a skilled artisan would have recognized that using the
method of Comb ' 140 to raise context-independent antibodies to sumoy lated
lysine would improve Dasso' s methods because different antibodies to each
target protein would not be needed.
Appellants also argue that "the combination of Dasso and Comb would
not have been understood to produce predictable results." Appeal Br. 5.
Appellants argue that "Dasso and Comb contain no teaching or suggestion of
the claimed motif-specific, context-independent antibodies that bind
sumoylated proteins" and "it would not have been known if such antibodies
could predictably be produced in view of Dasso and Comb." Id. at 5-6.
Appellants conclude that "[t]here is no reasonable expectation of success here
because it was uncertain and unpredictable [ifJ the claimed antibodies could
be produced in view of Dasso and Comb." Id.
This argument is unpersuasive for the reasons discussed above: Comb
'140 teaches that its method is generally applicable, and expressly suggests
applying its method to raise motif-specific, context-independent antibodies
to acetylated lysine and to amino acids modified with ubiquitin. Therefore, a
skilled artisan would have had a reasonable expectation of success in
combining the teachings of Comb '140 and Dasso.
Appellants also argue that "[t]he combination of Dasso and Comb
do[ es] not teach or suggest all elements of the claims" because "[ n ]either of
these references teaches a context-independent antibody that binds to a
SUMO motif." Appeal Br. 7. The issue with regard to§ 103, however, is not
whether any single reference teaches all of the limitations of the claimed
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invention, but whether the invention would have been obvious to a person of
ordinary skill in the art based on the teachings of the combined references.
See In re Young, 927 F.2d 588, 591 (Fed. Cir. 1991). For the reasons
discussed above, we conclude that the references would have made obvious
the claimed invention.
Appellants argue that, "[r]egarding claim 2, Dasso and Comb do not
teach or suggest an antibody that binds to a motif that comprises the
sequence xxxxxKxxxxx, where x is any amino acid and K is a sumoylated
lysine residue." Appeal Br. 9. Appellants make a similar argument with
respect to claims 19 and 20. Id. at 10.
These arguments are unpersuasive because Comb '140 teaches a
preferred embodiment in which motif-specific, context-independent
antibodies are raised using a peptide library "compris[ing]
XXXXXXJ*XXXXXXC where X=all 20 amino acids except cysteine and
J*=a modified(*) amino acid (J), for example, ... acetylated-lysine (K*)."
Comb ' 140 at 5: 3 8-40. Comb ' 140 also teaches that the modified amino acid
can be modified by ubiquitination. Id. at 5: 59-66. And Dasso teaches that
SUMO proteins form a modified lysine when they bind to a target protein;
specifically, a lysine bound via its E-amino group to the C-terminal glycine
of the SUMO protein. Dasso 3:9-13. Thus, although neither Dasso nor
Comb '140 expressly teaches the peptide recited in claim 2, their combined
teachings would have made the recited peptide obvious to a skilled artisan.
Regarding claims 3-5, Appellants argue that
Dasso does not teach or suggest context-independent
antibodies. Furthermore, Applicants note that Dasso does not
express a need or desire for motif-specific context-independent
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antibodies that can bind to sumoylated proteins. Therefore,
even though part of the claimed motifs may overlap with the
motifs of Dasso, Dasso clearly does not teach or suggest the
claimed antibodies because Dasso does not teach or suggest
context-independent antibodies that can bind to sumoylated
proteins.
Appeal Br. 9-10.
This argument is unpersuasive for the same reason discussed above
with respect to claim 1. To reiterate, the cited references need not expressly
suggest combining their teachings in order to make such a combination
obvious to those skilled in the art. See KSR Int 'l Co. v. Teleflex Inc., 550
U.S. 398,418 (2007): "Often, it will be necessary ... to look to interrelated
teachings of multiple patents ... in order to determine whether there was an
apparent reason to combine the known elements in the fashion claimed by
the patent at issue." Here, a skilled artisan would have recognized that
context-independent antibodies that bind sumoylated lysine, made using the
method of Comb ' 140, would improve Dasso' s methods because separate
antibodies to each target protein would not be needed.
Finally, with regard to claims 19 and 20, Appellants argue that
"[b Jecause no previously identified motif-specific, context-independent
antibodies that specifically bind to sumoylated proteins were present in the
prior art there was no way of predicting with a reasonable expectation of
success if their generation was even possible." Appeal Br. 10.
This argument is unpersuasive for the reason discussed above with
respect to claim 1: Comb '140 teaches that its method is generally
applicable, and expressly suggests applying its method to raise motif-
specific, context-independent antibodies to acetylated lysine and to amino
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acids modified with ubiquitin. These teachings would have provided a
skilled artisan with a basis for reasonably expecting that Comb '140 and
Dasso could be successfully combined.
We affirm the rejection of claims 1-5, 19, and 20 under 35 U.S.C.
§ 103(a) based on Dasso and Comb' 140. Claims 6-8 were not argued
separately and therefore fall with claim 1. 37 C.F.R. § 41.37(c)(l)(iv).
II
The Examiner has rejected all of the claims on appeal for
obviousness-type double patenting based on: (a) claims 1-5 of Comb '140 in
view of Dasso, (b) claims 1-9 of Comb '022 in view of Dasso, and
( c) claims 1-3 of Comb '714 in view of Dasso.
Appellants argue that the claims "are not obvious in view of' any of
the Comb patents and Dasso for the same reasons presented with respect to
the rejection under 35 U.S.C. § 103(a). Appeal Br. 10-11.
These arguments are unpersuasive for the reasons discussed above
with regard to the rejection under 35 U.S.C. § 103(a). We affirm all of the
rejections for obviousness-type double patenting.
SUMMARY
We affirm all of the rejections on appeal.
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. § l .136(a).
AFFIRMED
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