Ludivine Perrocheau et al.

Patent Trials and Appeals Board

Sep 27, 2021

2021000825 (P.T.A.B. Sep. 27, 2021)

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.
15/436,919 02/20/2017 Ludivine Perrocheau 13500043US2 7916
30743 7590 09/27/2021
W&C IP
11491 SUNSET HILLS ROAD
SUITE 340
RESTON, VA 20190
EXAMINER
FONTAINHAS, AURORA M
ART UNIT PAPER NUMBER
1649
MAIL DATE DELIVERY MODE
09/27/2021 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 LUDIVINE PERROCHEAU, ALAIN VAN DORSSELAER,
JOSE ALAIN SAHEL, and THIERRY LEVEILLARD

Appeal 2021-000825
Application 15/436,919
Technology Center 1600
Before RICHARD M. LEBOVITZ, ULRIKE W. JENKS, and
JAMIE T. WISZ, Administrative Patent Judges.

WISZ, Administrative Patent Judge.

DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims 10 and 12. We have jurisdiction under
35 U.S.C. § 6(b).
We REVERSE.

1 We use the word “Appellant” to refer to “applicant” as defined in
37 C.F.R. § 1.42. Appellant identifies INSERM (Institut National De La
Sante Et De La Recherche Medicale) and Centre National De La Recherche
Scientifique (CNRS) as the real parties-in-interest. Appeal Br. 3.
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CLAIMED SUBJECT MATTER
The Specification describes compounds that activate the BASIGIN
signaling pathway for treatment of degenerative disorders, including
neurodegenerative disorders such as retinitis pigmentosa. Spec. 1. The
Specification explains that BASIGIN is the RdCVF [Rod-derived Cone
Viability Factor] receptor and discloses a form of BASIGIN that has three
immunoglobulin-like domains in its extracellular portion and is expressed by
photoreceptor cones. Id. at 2, 3, 15. The Specification also discloses
screening methods for compounds that activate the BASIGIN signaling
pathway. Id. at 9–11.
Claim 10, the only independent claim, is illustrative of the claimed
subject matter and is reproduced below:
10. A method for screening BASIGIN pathway
activating compounds for the treatment of a retinal
neurodegenerative disorder comprising the steps of:
a) providing a plurality of neurons expressing BASIGIN
on their surface, wherein said neurons are cone photoreceptors,
wherein said BASIGIN contains three immunoglobulin-like
domains in its extracellular portion;
b) incubating said neurons with a candidate compound;
cl) determining whether said candidate compound binds
to BASIGIN and
c2) determining whether said candidate compound
activates BASIGIN by:
- determining neuron viability, wherein an increased
viability of neuron in a culture medium comprising the
candidate compound compared to a control without candidate
compound being indicative of an activation of BASIGIN;
and/or
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- analyzing a downstream molecular signaling pathway
by measuring an intracellular ATP content, wherein an
increased intracellular ATP content compared to a control
without candidate compound being indicative of an activation
of BASIGIN;
thereby determining whether said candidate compound
activates BASIGIN; and
d) selecting the candidate compound that binds to and
activates said BASIGIN.
Appeal Br. 22 (Claims App.).
REJECTION
The Examiner rejected claims 10 and 12 under 35 U.S.C. § 103 as
being unpatentable over Boulos2 in view of Ochrietor 20023 and Peachey.4
ISSUES AND ANALYSIS
The Examiner finds that “Boulos teaches a method for
screening/identifying a compound for neuroactivity by contacting CD147
(A.K.A. BASIGIN) and assessing binding or signaling.” Final Act. 3 (citing
Boulos 2:21–25, 20:27–29, 22:8–12). The Examiner also finds that “Boulos
teaches a method of controlling neurodegeneration by increasing CD147
receptor signaling on neurons” and “teaches CyPA, which works through

2 Sherif Boulos et al., WO 2006/084333 A1, published August 17, 2006
(“Boulos”).
3 Judith D. Ochrietor et al., “Inactivation of the Basigin gene impairs normal
retinal development and maturation,” 42 Vision Research, 447–53 (2002)
(“Ochrietor 2002”).
4 Neal S. Peachey & Sherry L. Ball, “Electrophysiological analysis of visual
function in mutant mice,” 107 Documenta Ophthalmologica, 13–36 (2003)
(“Peachey”).
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CD147, activates ERK1/2 in neuronal cultures and attenuates neuronal cell
death.” Id. (citing Boulos 5:5–9, 68:21–26). According to the Examiner,
“Boulos teaches that the neuroprotective agent, CyPA, prolongs the survival
of neurons in culture . . . and meets the requirement of determining neuron
viability as now required in instant claim 10.” Id. at 3–4 (citing Boulos
8:16–3, 66:10–14). The Examiner also finds that “Boulos teaches that given
the role of CD147 and CyPA conferring neural protection that it is possible
to screen patients with neurodegenerative conditions which include retinal
neurodegeneration.” Id. at 4 (citing Boulos 24:1–8, 25:3, 14). According to
the Examiner, “Boulos directly points to retinal degeneration which
encompasses retina cells including cone photoreceptor neurons.” Id.
The Examiner acknowledges that “Boulos does not specifically teach
using cone photoreceptors in the screening method” but finds that this
limitation is suggested by other references. Final Act. 4. Specifically, the
Examiner finds that “Ochrietor 2002 teaches BASIGIN (a.k.a. 5A11)
expression on the plasma membrane in Muller cells, retinal pigment
epithelium (RPE) cells and rod and cone photoreceptor cell bodies and their
inner segments.” Id. (citing Ochrietor 2002, 447). Although Ochrietor 2002
teaches that 5A11/BASIGN is an immunoglobulin-like glycoprotein, the
Examiner acknowledges that it does not teach that 5A11/BASIGN contains
three immunoglobulin-like domains. Id. (citing Ochrietor 2002, 447).
However, the Examiner finds that this is an inherent feature in
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5A11/BASIGN that is expressed in the neural retina as evidenced by
Ochrietor 2003.5
The Examiner finds that Ochrietor 2003 discloses that there are two
isoforms of 5A11/BASIGIN and that the BASIGIN-2 isoform is the
dominant isoform in the neural retina and is specifically expressed in the
neural photoreceptors. Id. at 4–5 (citing Ochrietor 2003, 4091, 4092, 4094,
Figs. 4, 7). The Examiner concludes that “Ochrietor 2002 teaches the 5A11
/BASIGIN that meets the limitations of instant claim 10 since the required
BASIGIN isoform is specifically found in the cells of interest, the
photoreceptors” but acknowledges that Ochrietor 2003 does not teach a
screening method. Id. at 5.
The Examiner also finds that “Peachey teaches visual loss associated
with hereditary retinal disorders such as retinitis pigmentosa” and that
“[r]etinitis pigmentosa (RP) usually follows a two-stage process in which
first the rod photoreceptors degenerate, then the cone photoreceptors, even
though the latter may not primarily be affected by the disease.” Id. (citing
Peachey 17, 18, 20). According to the Examiner:
Since cone photoreceptor cell death is secondary in retinitis
pigmentosa one of ordinary skill in the art would be motivated to
target cone photoreceptor cells as the cell to try and preserve in
this disease, since they are not the first cell type to die during the
progress of retinitis pigmentosa. Therefore, one of ordinary skill
in the art would be motivated to determine what drug acting

5 Judith D. Ochrietor et al., “Retina-Specific Expression of 5A11/Basign-2, a
Member of the Immunoglobulin Gene Superfamily,” 44 Investigative
Ophthalmology & Visual Science, 4086–96 (2003) (“Ochrietor 2003”).
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through BASIGIN would increase cone photoreceptor survival
in culture, as required in instant claim 10.
Id. at 5–6.
The Examiner concludes that it would have been prima facie obvious
for a person of ordinary skill in the art to arrive at the claimed invention
based on the disclosures of Boulos, Ochrietor 2002, and Peachey because
“Boulos provides an assay that can be used to screen for neuroprotective
agents, and that BASIGIN activation is a measure of neuronal viability.” Id.
at 6. Further, according to the Examiner, “a person of ordinary skill in the
art would have been motivated . . . to identify BASIGIN activators,” because
the cited references “teach that BASIGIN activation is crucial for neuronal
survival, particularly within retinal photoreceptor cells, and that such agents
could be used for the treatment of Retinitis Pigmentosa and other retinal
degenerative disorders.” Id.
Appellant argues that Boulos does not disclose the use of cone
receptors expressing BASIGIN with three Ig-like domains because Boulos
discloses a method for screening for compounds for neuroactivity using
cortical neurons, which do not express the same isoform of BASIGIN as
cone photoreceptors. Appeal Br. 14. According to Appellant, the isoform
mentioned in Boulos is BSG2 (Uniprot accession no. P35613-2, having two
Ig-like domains) and not BSG1 (Uniprot accession no. P23613-1, having
three Ig-like domains), as in the present invention. Id. Thus, according to
Appellant, “from the teachings of Boulos, there was no incentive to use
retinal photoreceptors, in particular cone photoreceptors, instead of cortical
neurons to screen for RdCVF analogs.” Id.
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Appellant further contends that “even if one skilled in the art would
have had reason to use retinal photoreceptors, he would have looked to
Ochrietor [2002] and Peachey, which comprise rods at 95%.” Id. Appellant
submits a Declaration under 37 C.F.R. § 1.132 of Dr. Thierry Leveillard
dated March 27, 2019 (“Leveillard Declaration”), which states that using
retinal photoreceptors in the method of Boulos “would never have worked to
select candidate analogs of RdCVF because the pathway involving Basigin
with three Ig-like domains is not activated in rods, contrary to cones.”
Leveillard Declaration 3.
We find that Appellant has the better position. The Examiner does not
provide sufficient evidence to show that it would have been obvious to one
of ordinary skill in the art at the time of the invention to use cone
photoreceptors to identify compounds that activate the BASIGIN isoform
which contains three immunoglobulin-like domains in its extracellular
portion. Neither Boulos, Ochrietor 2002, nor Peachey discloses the
BASIGIN isoform containing three immunoglobulin-like domains in its
extracellular portion. While Ochrietor 2003 does disclose this isoform, it
does not teach that the isoform is expressed on cone photoreceptors and
states that the isoform “has a very specialized, yet unknown, role within the
neural retina.” Ochrietor 2003, 4094. The Examiner contends that “one
would inherently use this receptor in cone photoreceptors in view of the
teachings already present in the art at the time of the instantly claimed
invention”; however, the Examiner does not cite to any reference in which
cone photoreceptors are selectively used in such screening assays nor does
the Examiner persuasively show that such modification is taught or
suggested by the prior art. Ans. 7.
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To the extent that the Examiner relies on the teachings of Ochrietor
2002 and Peachey to demonstrate that one of skill in the art would have used
retinal photoreceptors (containing rods and cones) in such screening assays,
the Leveillard Declaration states that these photoreceptors “comprise rods at
95%” and that using these retinal photoreceptors “would never have worked
to select candidate analogs of RdCVF because the pathway involving
Basigin with three Ig-like domains is not activated in rods, contrary to
cones.” Leveillard Declaration 3.
The Examiner responds that “[i]t would have been prima facie
obvious to one of ordinary skill in the art to choose either cone or rod
photoreceptors; such would amount to choosing from a finite number of
identified, predictable solutions, with a reasonable expectation of success.”
Ans. 10. However, the Examiner provides no persuasive evidence as to why
one of skill in the art would be motivated to selectively screen compounds
against rods and/or cones individually given that none of the cited references
disclose the function of the BASIGIN isoform with three immunoglobulin-
domains nor that this isoform is present on the cone photoreceptors.
The Examiner also argues that, because “cone photoreceptor cell
death is secondary in retinitis pigmentosa one of ordinary skill in the art
would be motivated to target cone photoreceptor cells as the cell to try and
preserve in this disease;” however, the Examiner cites to no persuasive
evidence to support this assertion. Final Act. 5. Again, the Examiner
provides no evidence for this assertion and the suggestion to screen cone
photoreceptors for compounds that activate the BASIGIN isoform with three
immunoglobulin domains is only supplied by improper hindsight. “We must
still be careful not to allow hindsight reconstruction of references to reach
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the claimed invention without any explanation as to how or why the
references would be combined to produce the claimed invention.”
Innogenetics, N.V. v. Abbott Labs., 512 F.3d 1363, 1374 n.3 (Fed. Cir. 2008).
Appellant also cites to evidence of objective indicia of
nonobviousness such as industry praise (see Appeal Br. 13), which does not
appear to have been fully addressed by the Examiner; however, we need not
address those arguments here because the evidence of record does not
support the Examiner’s assertions with regard to modifying the methods of
Boulos as discussed above.
Thus, for the reasons discussed above, we do not sustain the rejection
of claims 10 and 12 as being unpatentable over Boulos, Ochrietor 2002, and
Peachey.
DECISION SUMMARY
In summary:
Claim(s)
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
10, 12 103(a) Boulos, Ochrietor
2002, Peachey
10, 12

REVERSED