DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
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.
Priority
The present application is filed as a Divisional of application No. 16/209/100, filed 12/04/2018 (Patent US 11,768,202). Application No. 16/209,100 is a continuation of 15/157,949, filed 05/18/2016 (abandoned), which is a continuation of 13/718,288, filed 12/18/2012 (abandoned). Application 13/718,288 claims benefit under 35 U.S.C. 119(e) to provisional application No. 61/579,546, filed 12/22/2011.
Status of the Claims
Claims 1-10 are pending; claim 1 is amended; claims 9 and 10 are newly recited; claims 1-10 are examined below.
Withdrawn Objections/Rejections
The previous objections to the claims are withdrawn in response to Applicant’s amendments to the claims.
The previous rejections of claims under 35 U.S.C. 112(b) are withdrawn in response to amendments to the claims.
The previous rejection of claim under 35 U.S.C. 112(a), regarding scope of enablement, is withdrawn in response to Applicant’s amendments to the claims.
The previous rejection of claims under 35 U.S.C. 101 is withdrawn in response to Applicant’s amendments to the claims.
The previous rejection of claims under 35 U.S.C. 102 and under 35 U.S.C. 103 are withdrawn in response to Applicant’s amendments to the claims, however, see new grounds as set forth in detail above.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-10 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Black et al., Serologic survey of adult patients with obsessive-compulsive disorder for neuron-specific and other autoantibodies, Psychiatry Research, 81, (1998) (IDS entered 09/25/2023) in view of Harlow, E. and Lane, D., Antibodies: A Laboratory Manual (1988) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pg. 175, Virginie Dormoy-Raclet, Virginie Dormoy-Raclet ; Imed-Eddine Gallouzi, ELAVL1 (ELAV (embryonic lethal, abnormal vision, Drosophila)-like 1 (Hu antigen R)), Atlas Genet Cytogenet Oncol Haematol. 2008-09-01, Available Online: http://atlasgeneticsoncology.org/gene/44237/elavl1-(elav-(embryonic-lethal-abnormal-vision-drosophila)-like-1-(hu-antigen-r)) (13 pages), Musunuru et al., Paraneoplastic opsoclonus-myoclonus ataxia associated with non-small-cell lung carcinoma, J. Neurooncol., 90(2), (2008), p. 213-216, Kashyap et al., Enteric Autoantibodies and Gut Motility Disorders, Gastroenterol. Clin. North. Am., 37(2), (2008), p. 297-410, Totland et al., CDR2 antigen and Yo antibodies, Cancer Immunol. Immunother., 60, (2011), p. 283-289 and Peters et al., Abstract 84: Abstracts of the 106th Annual Meeting of the German Society for Pediatrics and Adolescent Medicine (DGKJ), (2010) (Machine English Translation obtained via Google Scholar, 2 pages) (cited previously).
Black et al. teach serum immunoassay (obtaining a serum sample) to detect a panel of autoantibodies, specifically looking to detect neuron-specific autoantibodies, as well as other organ and non-organ specific autoantibodies (see abstract). See at page 375, col. 2, para 2, Black describe detection of anti-Yo antibodies, anti-Hu antibodies and anti-Ri antibodies by indirect immunofluorescence methods.
Black fails to disclose the specific details/steps of their indirect immunofluorescence methods, and as such fails to teach contacting sample with one or more antigens from those recited to form one or more antigen-autoantibody complexes, contacting with labeled secondary antibody to form one or more labeled antigen-autoantibody complexes, and detect the labeled complex to determine the presence of one or more autoantibodies.
Further, although Black recognizes PANDAS as those patients with evidence of recent group A beta hemolytic streptococcal infection, Black is referring to patients with pediatric onset obsessive compulsive disorder and tic syndromes, Black recognizing that a subset of these patients have symptom onset or exacerbation associated with infection (see abstract). Black at table 1 describes their adult patients and does not clearly indicate the method performed on subjects having previously had streptococcal infection (does not clearly indicate the samples tested by Black include those having had confirmed streptococcal infection).
Generally, regarding indirect immunofluorescence assays for the detection to an antibody target, see for example, Harlow and Lane at page 175, under “Antibody Capture Assays”, in an antibody capture assay, first antigen is bound to a solid substrate, target is allowed to bind, followed by washing to remove unbound antibody, then bound antibodies are detected using secondary reagent that specifically recognizes the antibody.
Regarding the antigens immobilized to achieve indirect detection of anti-Yo, anti-Hu and anti-Ri antibodies, see for example Virginie Dormoy-Raclet , ELAVL1 is recognized as Hu antigen R, antigen which anti-Hu antibody binds. See Musunuru et al., it is known that anti-Ri antibodies bind Nova antigens (Nova-1 and Nova-2, see page 213, para 1). Finally, see Kashyap et al., at page 3, para 2, it is known that autoantibody that is anti-Yo autoantibody targets a neuronal signal transduction protein, Cdr antigen. Additionally, see Totland et al., abstract, specifically Cdr2 protein is antigen to anti-Yo antibody.
Peters et al. abstract teach there are 5 criteria for diagnosing PANDAS, 1. Onset after the age of 3, but before puberty; 2. Presence of obsessive-compulsive symptoms and/or tics; 3. Sudden onset and/or episodic course; 4. Temporal association between GABHS infection and symptom worsening; 5. Choreiform movements during symptom worsening.
Peters et al. describe a patient (11 year old boy) who is diagnosed as having PANDAS, but who did not have anti-Hu or anti-Ma (antineuronal type) antibodies. Although their patient did not present with anti-Hu or anti-ma antibodies, Peters does teach that cross-reactive antibodies have been bound, and there is evidence of structural changes in MRI reflecting the inflammatory process as well as in vitro models suggesting a direct pathogenic effect of the antineuronal antibodies.
Therefore, although their patient did not present with such antibodies, these anti-neuronal antibodies were recognized in the prior art as occurring. Peters et al. is teaching diagnosis of the disease PANDAS based on the 5 criteria, and Peters is determining the presence or absence of one or more autoantibodies (in the case of Peters, is teaching absence of anti-Hu and anti-Ma) in a biological sample from the subject, the subject having previously had a Streptococcal infection.
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention, that the assay of Black (indirect immunofluorescence assay) comprise contacting sample containing antibody with antigen, detecting bound complex using labeled secondary antibody because it was known in the art that this type of assay is performed in this way (see for example Harlow and Lane), and further that the immunofluorescent immunoassay of Black include contacting sample with antigen for each of the antibodies (for example, ELAV1, Nova1 and/or 1, and at least Cdr2 as taught by each of Virginie Dormoy-Raclet, Musunuru et al., Kashyap et al., and Totland, respectively) as an obvious matter of applying a known technique for a known method, specifically because each of these are art recognized, known antigens available to those of ordinary skill in the art for binding/detecting the anti-neuronal anti-Hu, anti-Ri and anti-Yo antibodies of Black et al. One having ordinary skill in the art would have a reasonable expectation of success because Black does not specify the antigens used for assay, and because one would expect success using a known antigen reagent known to bind.
Regarding the limitations “subject having or previously having a streptococcal infection” and “biological sample comprising autoantibodies”, it would have been prima facie obvious to one having ordinary skill in the art to have performed the method of Black of samples from subjects including those having PANDAS (said subject’s previously having had a streptococcal infection), that at least some of these subjects are expected to present samples with autoantibodies because it is known in the art (both Black and Peters), the art suggesting detection of these antibodies with the onset/exacerbation of symptoms. One having ordinary skill in the art would have a reasonable expectation of success because it was already known in the art at the time that some of these patients exhibit these antibodies, that these antibodies can correlate with their diagnoses.
Regarding claim 2, see above, the cited art teach autoantibodies including anti-Hu, anti-Ri and anti-Yo.
Regarding claims 3-4, the cited art addresses antigens from those selected at claims 3 and also 4.
Regarding claims 5-7, see the combination of the cited art addresses samples from those with PANDAS (human, pediatric subjects).
Regarding claims 8 and 9, the combination of the cited art teaches serum, and immunofluorescence assay.
Regarding claim 10, see as cited, the combination of the cited art teaches PANDAS.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3 and 5-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 11,768,202.
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending similarly teaches a method of detecting autoantibodies in a subject having or previously ahving streptococcal infection, the method comprising obtaining a sample (see claim 1), testing for autoantibodies to antigen for Nova-1 or Nova 2 (anti-Ri autoantibody).
See the method of ‘202 comprises contacting with antigen, and contacting with secondary labeled antibody because ‘202 similarly teach immunofluorescence assay, which as evidenced by Harlow and Lane, comprises such steps (see Harlow and Lane cited previously above).
Regarding claim 2, see ‘202 teaching anti-Ri (‘202 at claim 1).
Regarding claim 3, ‘202 teach Nova-1 and Nova-2 (claim 1).
Regarding claims 5 and 10, see ‘202 teach PANDAS (claim 1).
Regarding claim 6, see ‘202 claim 5 (human)
Regarding claim 7, see ‘202, claim 6 (pediatric).
Regarding claim 8, see ‘202 claim 7 (blood, serum and plasma).
Regarding claim 9, see ‘202 claim 1 (immunofluorescence assay).
Response to Arguments
Applicant's arguments filed 07/22/2026 have been fully considered but they are not persuasive for the following reasons.
See as indicated in detail previously above, rejections under 35 U.S.C. 112(a), 35 U.S.C. 112(b) and 35 U.S.C. 101 are withdrawn in response to amendments to the claims. As such, arguments at remarks pages 5-17 are moots as they are directed to rejections no longer pending.
Regarding the rejection of claims under 35 U.S.C. 102, the rejection is withdrawn in response to Applicant’s amendments to the claims, however the reference is still cited in the new grounds set forth under 35 U.S.C. 103.
Regarding remarks at pages 18-19, the previous rejection of claim 8 over Peters in view of Black is withdrawn in response to amendments to the claims. However, see new grounds set forth in detail above.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELLEN J MARCSISIN whose telephone number is (571)272-6001. The examiner can normally be reached M-F 8:00am-4:30pm.
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/ELLEN J MARCSISIN/ Primary Examiner, Art Unit 1677
