DETAILED ACTION
Preliminary Amendment filed on 10/06/2023 is acknowledged. Claims 4, 7, 9-16, 19, 25-26, 28-37, 39-45, 47-77, 79-80, 83-84 and 86-98 are cancelled. Claims 1-3, 5-6, 8, 17-18, 20-24, 27, 38, 46, 78, 81-82 and 85 are pending in the application and are considered on merits.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-3, 5-6, 8, 17-18, 20-24, 27, 38, 46, 78, 81-82 and 85 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nomoto et al. (PNAS, 2021) (Nomoto).
Regarding claim 1, Nomoto teaches a method for determining an increased risk for a cognitive disorder in a human subject (abstract), comprising:
collecting a biological sample from the human subject, wherein the biological sample is a blood, saliva, urine, serum, tears, skin, tissue, or hair from the human subject (abstract);
determining, by an assay, a level of collapsing response mediator protein-2 (CRMP2) in the biological sample, wherein the assay is a proteomic assay and
comprises (abstract):
i. contacting the biological sample with an agent that recognizes CRMP2 (abstract), and
ii. measuring the level of bound CRMP2 and thereby determining the level of CRMP2 present in the biological sample, wherein the agent that recognizes CRMP2 is an antigen-binding agent (abstract); and
detecting the level of CRMP2 (abstract).
Regarding claim 2, Nomoto teaches that where in the assay further comprises:
i. contacting the biological sample with an agent that recognizes
phosphorylated CRMP2 (p-CRMP2) (abstract),
ii. measuring a level of bound p-CRMP2 and thereby determining the level
of p-CRMP2 present in the biological sample (abstract); and
iii. detecting the level of p-CRMP2 (abstract).
Regarding claim 3, Nomoto teaches that the method further comprising:
a. computing a ratio of the p-CRMP2 to CRMP2 (p-CRMP2:CRMP2 ratio); and
b. detecting a reduced p-CRMP2:CRMP2 ratio in comparison to a reference pCRMP2:CRMP2 ratio (abstract).
Nomoto also anticipates claims 3, 5-6, 8, 17-18, 20-24, 27, 38, 46, 78, 81-82 and 85.
Examiner notice that Nomoto paper states that “M.N., G.T.K., F.M.B., J.T.C., R.L.S., Y.H., E.Y.S., and Y.G. designed research”. Since E.Y.S. (Evan Y. SNYDER) is the sole inventor of this application, the applicant needs to file a declaration to prove that the other co-authors, who designed research in Nomoto paper, do not contribute to the claimed subject matter, in order to disqualify Nomoto paper as a prior art.
Claim(s) 1-2, 17-21, 27, 46, 78 and 85 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Giraudon (WO 2011/007209).
Regarding claim 1, Giraudon teaches a method for determining an increased risk for a cognitive disorder in a human subject (abstract), comprising:
collecting a biological sample from the human subject, wherein the biological sample is a blood, saliva, urine, serum, tears, skin, tissue, or hair from the human subject (page 10, line 28-33);
determining, by an assay, a level of collapsing response mediator protein-2 (CRMP2) in the biological sample, wherein the assay is a proteomic assay and
comprises (page 2, lines 22-29):
i. contacting the biological sample with an agent that recognizes CRMP2 (page 14, lines 25-29), and
ii. measuring the level of bound CRMP2 and thereby determining the level of CRMP2 present in the biological sample, wherein the agent that recognizes CRMP2 is an antigen-binding agent (page 14, line 25-29); and
detecting the level of CRMP2 (page 14, lines 25-29).
Regarding claim 2, Giraudon teaches that where in the assay further comprises:
i. contacting the biological sample with an agent that recognizes
phosphorylated CRMP2 (p-CRMP2) (page 15, lines 2-7),
ii. measuring a level of bound p-CRMP2 and thereby determining the level
of p-CRMP2 present in the biological sample (page 15, lines 2-7); and
iii. detecting the level of p-CRMP2 (page 15, line 2-7).
Regarding claim 17, Giraudon teaches that wherein the proteomic assay is immunoassay, mass spectrometry, or intracellular flow cytometry (page 14, lines 25-29).
Regarding claim 18, Giraudon teaches that wherein the immunoassay is selected from western blotting, dot blotting, quantitative enzyme-linked immunosorbent assays (ELISA), immunocytochemistry (ICC), immunohistochemistry (IHC), protein multiplex assay, or lateral flow test (page 14, lines 25-29).
Regarding claim 20, Giraudon teaches that wherein the antigen-binding agent that recognizes CRMP2 is an anti-CRMP2 antibody; and the antigen-binding agent that recognizes p-CRMP2 is an anti-p-CRMP2 antibody (page 5, lines 14-15).
Regarding claim 21, Giraudon teaches that wherein the antigen-binding agent that recognizes CRMP2 is an anti-CRMP2 monoclonal antibody (page 5, line 14-20);
and the antigen-binding agent that recognizes p-CRMP2 is an anti-p-CRMP2 monoclonal antibody (page 5, line 14-20).
Regarding claim 27, Giraudon teaches that wherein the CRMP2 is phosphorylated at Serine 522 (p-S522-CRMP2) (page 2, par 1), wherein measuring the level of p-CRMP2 comprises measuring a phosphorylation of CRMP2 at Serine 522 (page 15, par 2).
Regarding claim 46, Giraudon teaches a method comprising:
collecting a biological sample from a human subject (page 10, line 28-33);
determining, by an assay, a level of CRMP2 in the biological sample from the
subject, wherein the assay comprises:
i. contacting the biological sample with an agent that recognizes CRMP2 (page 14, lines 25-29),
ii. measuring the level of bound CRMP2 and thereby determining the level of CRMP2 present in the biological sample (page 14, lines 25-29).
iii. compute the risk (prognosis) of the human subject having a cognitive disorder based on determining the level of CRMP2 in comparison to a reference level of CRMP2 (page 2, lines 30-33); and
administering a therapeutic agent (treatment) to the human subject (page 12, lines 21-23).
wherein the therapeutic agent is configured to mitigate or alleviate one or more symptoms of the cognitive disorder in the human subject (page 12, line 21-23).
Regarding claim 78, Giraudon teaches a method of treating a cognitive disorder in a human subject, comprising:
performing the method as in claim 1; and
administering a therapeutic agent or clinical investigational product to the human subject (page 1, line 21-27).
Regarding claim 85, Giraudon discloses a kit comprising:
a. one or more agents to collect a biological sample from a human subject (page 10, line 28-33);
b. one or more agents to measure a level of CRMP2 and a level of p-CRMP2 from the biological sample obtained from the subject (page 14, line 25-29); and
c. an instruction to collect the biological sample and measure the levels of CRMP2 and p-CRMP2 using the agents in the kit (page 14, line 25-29).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 3, 5-6, 8, 22-24, 38 and 81-82 is/are rejected under 35 U.S.C. 103 as being unpatentable over Giraudon (WO 2011/007209) in view of Gammon (Neuroscience News, 2021).
Regarding claim 3, Giraudon does not specifically teach that the method further comprising:
a. computing a ratio of the p-CRMP2 to CRMP2; and
b. detecting a reduced p-CRMP2:CRMP2 ratio in comparison to a reference pCRMP2:CRMP2 ratio.
However, Gammon teaches
a. computing a ratio of the p-CRMP2 to CRMP2 (page 2); and
b. detecting a reduced p-CRMP2:CRMP2 ratio in comparison to a reference pCRMP2:CRMP2 ratio (page 2).
Gammon teaches that “Previous research has shown that most people maintain an even balance between the two forms of CRMP2: its active, non-phosphorylated form and its inactive, phosphorylated form. …The findings indicated that the amount of active CRMP2 was too high in people with schizophrenia and, at least in young people with schizophrenia, was not balanced by an appropriate amount of increased inactive CRMP2. That imbalance between active and inactive CRMP2 could account for some dysfunctions in neural connections. Measuring an abundance of active CRMP2, particularly if its ratio with inactive CRMP2 is too low, could become a format for a rapid, minimally invasive blood test to support the diagnosis of schizophrenia” (page 2). Thus, it would have been obvious to one of ordinary skill in the art to
a. computing a ratio of the p-CRMP2 to CRMP2 (p-CRMP2:CRMP2 ratio); and
b. detecting a reduced p-CRMP2:CRMP2 ratio in comparison to a reference pCRMP2:CRMP2 ratio,
in order to diagnose schizophrenia.
Regarding claim 5, Gammon teaches that wherein the cognitive disorder is Schizophrenia (SCZ). Gammon teaches that “The findings indicated that the amount of active CRMP2 was too high in people with schizophrenia and, at least in young people with schizophrenia, was not balanced by an appropriate amount of increased inactive CRMP2. That imbalance between active and inactive CRMP2 could account for some dysfunctions in neural connections. Measuring an abundance of active CRMP2, particularly if its ratio with inactive CRMP2 is too low, could become a format for a rapid, minimally invasive blood test to support the diagnosis of schizophrenia.” (page 2). Thus, it would have been obvious to one of ordinary skill in the art to use the level of CRMP2 as a biomarker for Schizophrenia (SCZ). The result is predictable.
Regarding claim 6, Gammon teaches that wherein the SCZ is an early stage of SCZ (title, page 3).
Regarding claim 8, Giraudon teaches that wherein the biological sample is a blood sample from the human subject comprising peripheral blood mononuclear cells (PBMC) (e.g. lymphocytes) (page 10, lines 28-32).
Gammon also teaches that wherein the biological sample is a blood sample from the human subject comprising peripheral blood mononuclear cells (PBMC) (e.g. lymphocytes) (page 2, par 1).
Regarding claim 22, Gammon teaches identifying the human subject with added risk of having the cognitive disorder if the pCRMP2:
CRMP2 ratio of the subject is decreased compared to the reference pCRMP2:CRMP2 ratio (page 2).
Regarding claim 23-24, Gammon teaches that the method as in claim 22 comprising identifying the human subject with added risk of having the cognitive disorder if the p-CRMP2:CRMP2 ratio of the subject is lower than the reference (page 2). It would have been obvious to one of ordinary skill in the art to optimize the range of the ratio by routine experimentation.
Regarding claim 38, it is conventional to treat schizophrenia human subject with one or more antipsychotic drugs.
Regarding claim 81, Gammon teaches that wherein the cognitive disorder is Schizophrenia (SCZ). Gammon teaches that “Measuring an abundance of active CRMP2, particularly if its ratio with inactive CRMP2 is too low, could become a format for a rapid, minimally invasive blood test to support the diagnosis of schizophrenia.” (page 2). Vesicular monoamine transporter 2 (VMAT2) inhibitor are known therapeutic agent or clinical investigational product for treating Schizophrenia.
Regarding claim 82, the VMAT2 inhibitor Valbenazine, or Tetrabenazine are known therapeutic agent or clinical investigational product for treating Schizophrenia.
Conclusion
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/XIAOYUN R XU, Ph.D./ Primary Examiner, Art Unit 1797