NORTHWESTERN UNIVERSITY

Patent Trials and Appeals Board

Oct 30, 2020

13676806 - (D) (P.T.A.B. Oct. 30, 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.
13/676,806 11/14/2012 Grant A. Krafft API0005US . C3 6846
26259 7590 10/30/2020
LICATA & TYRRELL P.C.
66 E. MAIN STREET
MARLTON, NJ 08053
EXAMINER
EMCH, GREGORY S
ART UNIT PAPER NUMBER
1699
NOTIFICATION DATE DELIVERY MODE
10/30/2020 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):
PTOactions@licataandtyrrell.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
_________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
_________________

Ex parte GRANT A. KRAFFT, WILLIAM L. KLEIN, BRETT A.
CHROMY, LEI CHANG, MARY P. LAMBERT, and KIRSTEN L. VIOLA

_________________

Appeal 2020-000738
Application 13/676,806
Technology Center 1600
_________________

Before RICHARD M. LEBOVITZ, DEBORAH KATZ, and
JOHN A. EVANS, Administrative Patent Judges.

KATZ, Administrative Patent Judge.

DECISION ON APPEAL
Appellant1 seeks our review,2 under 35 U.S.C. § 134(a), of the
Examiner’s decision to reject claims 1–5, 7, 8 and 10. We have jurisdiction
under 35 U.S.C. § 6(b). We AFFIRM.

1 We use the word “Appellant” as defined in 37 C.F.R. § 1.42. Appellant
identifies the real party-in-interest as Northwestern University. (Appeal Br.
1.)
2 We consider the Final Office Action issued September 7, 2018 (“Final
Act.”), the Appeal Brief filed April 29, 2019 (“Appeal Br.”), the Examiner’s
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The Examiner rejects claims 1–5, 7, 8 and 10 under 35 U.S.C. §
103(a) as unpatentable over Schenk,3 Krafft,4 and Chromy.5 (See Final Act.
3–5.)
Appellant’s Specification explains there is a general consensus that
high levels of the longer form of amyloid peptide (“Aβ”) is responsible for
Alzheimer’s disease. (See Spec. 2:16–19.) The Specification explains,
further, that amyloid beta (Aβ)-derived diffusible ligands (“ADDLs”)
comprise small, soluble Aβ oligomers as trimers and tetramers and higher-
order species. (See id. at 3:24–25.) In addition to the ADDLs, Aβ exists as
smaller monomers and larger, full-sized neurotoxic fibrils. (See id. at 3:1–
23.) The Specification states that the invention is of antibodies that are
generated and selected for the ability to bind ADDLs specifically, without
binding to Aβ monomer or fibrils. (See id. at 6:25–27.)
Appellant’s claim 1 recites:
A method for producing an amyloid beta-derived diffusible
ligand (ADDL) neutralizing antibody comprising
(a) injecting ADDLs into an animal to induce an immune
response to the ADDLs;
(b) isolating antibodies that selectively and specifically bind to
ADDLs;
(c) identifying antibodies of (b) that neutralize ADDL
neurotoxicity in vitro in a long-term potentiation assay or cell viability
assay;

Answer issued on September 11, 2019 (“Ans.”), the Reply Brief filed
November 6, 2019 (“Reply Br.”).
3 Schenk, U.S. Patent 6,743,427 B1, issued June 1, 2004.
4 Krafft et al., International Patent Application Publication WO 01/10900
A2, published February 15, 2001.
5 Chromy et al., Degenerative Disease: Alzheimer’s – Beta Amyloid:
Aggregation 26 SOCIETY FOR NEUROSCIENCE 1284 abstract 475.8 (2000).
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(d) selecting antibodies of (c) that do not bind to monomeric
amyloid beta peptide;
(e) identifying antibodies of (d) that detect 5 pmol of ADDLs in
a sample comprising ADDLs; and
(f) humanizing the antibodies of (e) thereby producing an
ADDL neutralizing antibody.

(Appeal Br. 17.) Appellant does not argue for the separate patentability of
any of the rejected claims in the Appeal Brief. Accordingly, we focus on
claim 1 in our review. See 37 C.F.R. § 41.37(c)(1)(iv).

Findings of Fact
1. Schenk teaches a method for producing Aβ neutralizing
antibodies by injecting aggregated Aβ into an animal to induce an immune
response, isolating antibodies that bind to the aggregated Aβ, and
humanizing the identified antibodies. (Schenk 15:8–16:39, col. 63, Table
17; see Final Act. 3.)
2. Schenk teaches producing antibodies that detect Aβ at the pMol
range. (See Schenk col. 63, Table 17; see Final Act. 3.)
3. Schenk fails to teach selecting antibodies that do not bind to
monomeric Aβ or to Aβ fibrils and does not teach that Aβ comprises
ADDLs. (See Final Act. 3.)
4. Krafft teaches Aβ-derived ADDLs comprising Aβ protein
assembled into globular non-fibrillar oligomeric structures. (See Krafft
Abstract; see Final Act. 3.)
5. Krafft teaches producing ADDLs. (See Krafft 17:28–18:11; see
Final Act. 4.)
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6. Krafft teaches identifying compounds that neutralize toxicity
caused by ADDLs by contacting a culture of neuronal cells with ADDLs in
the presence of the compounds and measuring cell viability. (See Krafft
25:17–26:2.)
7. Krafft teaches detecting ADDL protein assembly in a test
material by contacting the test material with an antibody that binds to
oligomeric Aβs. (See Krafft 18:25–27, 21:18–23, 26:24–25; see Final Act.
4.)
8. Krafft does not teach producing anti-ADDL antibodies or
selecting antibodies that do not bind to monomeric Aβ or to amyloid fibrils.
(See Final Act. 4.)
9. Chromy teaches that fibrils, protofibrils, and ADDLs are
neurotoxic and that a “new oligomer specific antibody” had been made. (See
Chromyl see Final Act. 4.)
10. Chromy teaches that the oligomer-specific antibody can be used
to discriminate between ADDLs and protofibril species, whereas other
techniques, such as silver staining cannot. (See Chromyl see Final Act. 4.)

Analysis
We agree with the Examiner that Schenk, Krafft, and Chromy teach a
general method of producing antibodies directed to Aβ, a method of
producing ADDLs, and method of assaying for neutralizing ADDLs. (See
Final Act. 3–5.) From these factual findings, the Examiner determines that
one of ordinary skill in the art would have considered it desirable to produce
Aβ antibodies to treat amyloid disease because Schenk teaches making Aβ
antibodies to treat Alzheimer’s disease and Krafft teaches that ADDL is
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toxic. (See id. at 5.) The Examiner also determines that those of ordinary
skill would have considered it obvious to select antibodies specific for
ADDLs, as opposed to monomeric Aβ peptide or Aβ fibrils, because
Chromy teaches that ADDLs are toxic and because ADDLs can be
distinguished from other Aβ species. (See id.) The Examiner finds that
there would have been a reasonable expectation of success from these
teachings.
Appellant argues that the Specification teaches isolating antibodies
that selectively and specifically bind to ADDLs, as required in step (b) of
claim 1, by assaying an antibody for its ability to bind proteins in whole
brain/CSF homogenates, proteins on the cell surface, Aβ monomers and Aβ
fibrils. (See Appeal Br. 9–10, citing Spec. 19:8–18, 20:19–22; 21:18–19;
90:28–91:1, and 109:1–14.) Appellant argues that the cited prior art,
specifically Schenk, does not teach isolated antibodies that selectively and
specifically bind to ADDLs. (See Appeal Br. 10, 12, 14.) According to
Appellant, “the Examiner merely postulated as to why one of ordinary skill
in the art at the time of the invention would have found step (b) of the
claimed method obvious, without any teachings from the prior art to support
this rejection.” (Appeal Br. 10.)
We are not persuaded by Appellant’s argument because Chromy
teaches antibodies that specifically recognize ADDLs from other Aβ forms,
disclosing or reasonably suggesting to make ADDL specific antibodies.
(See Final Act. 4; see Ans. 8.) Although Chromy does not describe the
methods by which ADDL antibodies were produced, claim 1 is not limited
to the methods described in Appellant’s Specification, such as assaying the
ability to bind proteins in whole brain/CSF homogenates. Schenk
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demonstrates that it was well known in the art how to obtain antibodies that
specifically bind one structure and not another and we are not persuaded that
step (b) recites anything that would not have been obvious to one of ordinary
skill. (See Ans. 7.)
Appellant also argues that Schenk does not teach identifying
antibodies that neutralize ADDL neurotoxicity in vitro as required in step (c)
of claim 1. (See Appeal Br. 10–11.) Appellant argues that Schenk teaches
screening for the clearing activities of antibodies instead. (See id. at 11.)
We are not persuaded by this argument because Krafft teaches
identifying compounds that neutralize toxicity caused by ADDLs by
contacting a culture of neuronal cells with ADDLs in the presence of the
compounds. (See Ans. 9.) Thus, although Schenk does not teach selection
of agents with assays for neutralizing ADDL activity, Krafft does. “Non-
obviousness cannot be established by attacking references individually
where the rejection is based upon the teachings of a combination of
references.” In re Merck & Co., Inc., 800 F.2d 1091, 1097 (Fed. Cir. 1986).
Appellant argues further that the Examiner errs by asserting “that it
would have been obvious to one of ordinary skill in the art that antibodies
which are specific for ADDLs and do not bind monomeric amyloid beta
peptide or amyloid fibrils would be of use as potential therapeutics against
endogenous oligomeric amyloid beta” (See Appeal Br. 11.) Appellant cites
to the testimony of William Goure, Ph.D., that
[w]hile portions of the individual steps of the claimed method had
been separately disclosed prior to the instant invention, what was not
known at the time of the instant invention was whether antibodies
generated using synthetic ADDLs as an antigen would bind
endogenous soluble Aβ oligomers in human (or other mammalian)
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fluid or tissue samples or what the levels of endogenous soluble Aβ
oligomers were in human (or other mammalian) fluid or tissue
samples.

(Declaration of Dr. William Goure, filed September 22, 2017 (“2017 Goure
Decl.”), ¶ 3; see Appeal Br. 11.)
We are not persuaded by Appellant’s argument or by Dr. Goure’s
testimony because claim 1 does not require using antibodies made by the
claimed method as therapeutics and does not require binding to endogenous
soluble Aβ oligomers. Rather, the claim is directed to making the antibody
and recites the step of “(e) identifying antibodies of (d) that detect 5 pmol of
ADDLs in a sample comprising ADDLs.” Thus, Appellant’s argument is
directed to limitations that do not appear in the rejected claims.
We are also not persuaded by this argument because it was known that
ADDL could be produced and methods of making antibodies were well
known. Schenk teaches the desirability of making antibodies against Aβ and
Chromy teaches the desirability of making antibodies that distinguish ADDL
from other forms of Aβ. (See Ans. 6.)
When there is a design need or market pressure to solve a problem
and there are a finite number of identified, predictable solutions, a
person of ordinary skill has good reason to pursue the known options
within his or her technical grasp. If this leads to the anticipated
success, it is likely the product not of innovation but of ordinary skill
and common sense. In that instance the fact that a combination was
obvious to try might show that it was obvious under § 103.
KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 421 (2007). We are persuaded
by what is taught in the prior art that Appellant’s method of doing so would
not have been at least obvious to try.
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Appellant argues that Chromy does not provide details of the
preparation of the antibody or details such as its “binding characteristics and
selectivity” or how it was prepared. (See Appeal Br. 14.) We disagree that
the relevant details of the antibody in Chromy are not taught because
Chromy teaches an oligomer-specific antibody and that “[t]he use of several
antibodies illuminate conformational differences between the oligomers and
protofibrils that are not visible using silver staining techniques.” (Chromy.)
Similarly, in the Reply Brief, Appellant argues that Chromy does not teach
or suggest an antibody that selectively and specifically binds to ADDLs and
does not bind monomeric Aβ peptide or amyloid fibrils, as recited in claims
7 and 8 is unpersuasive in view of the characterization of the antibody as
“oligomer-specific.”6 (See Reply Br. 2.)
Appellant relies on Dr. Goure’s testimony to argue that the field of Aβ
protins was relatively immature at the time of filing and that the combined
teachings of these references would have only suggested the development of
antibodies to a heterogenous population of Aβ species. (See Appeal Br. 15,
citing Declaration of Dr. William Goure filed May 16, 2018 (“2018 Goure
Decl.”), ¶¶ 8 and 9.) The cited portion of Dr. Goure’s testimony, though,

6 We note that many of the inventors named on the current application
appear to be co-authors of Chromy. Thus, Appellant likely has specific
knowledge of how the oligomer-specific antibody discussed in Chromy was
made. Appellant does not argue that the method used was beyond the skill
of an ordinary artisan or did not use the methods recited in Schenk and
Krafft. Accordingly, Chromy is strong evidence that one of ordinary skill in
the art would have had a reasonable expectation of success in developing a
method to produce an antibody as claimed. (See Ans. 11.)

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fails to address the teaching in Chromy of an antibody that binds to ADDL.
Although Dr. Goure refers to Chromy for its teachings of the different forms
of Aβ, he fails to discuss the oligomer-specific antibody reported in Chromy.
(See 2018 Goure Decl. ¶¶ 3 and 4.)
In the Reply Brief Appellant argues that knowledge of the different
forms of Aβ and the teachings of Schenk would have motivated one of
ordinary skill to make an antibody against all forms of Aβ, not one selective
for ADDLs. (See Reply Br. 2.) We are not persuaded by this argument
because even if there was a reason to make non-selective antibodies against
Aβ forms, Krafft and Chromy teach that ADDLs were known to be
neurotoxic. (See Krafft 25:17–26:2 (teaching compounds that modulate the
neurotoxicity of ADDLs); see Chromy.) Thus, we are persuaded there
would have been a reason to make an antibody selective this form as well.
Appellant fails to present any argument persuading us that the
Examiner erred.
Conclusion
Upon consideration of the record and for the reasons given, we affirm
the Examiner’s rejection.
In summary:
Claims
Rejected
35 U.S.C.
§
Basis/References Affirmed Reversed
1–5, 7, 8, 10 103(a) Schenk, Krafft,
Chromy
1–5, 7, 8, 10
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136.
AFFIRMED