DETAILED ACTION
Comments
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . 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.
Claims 1, 6-8, 11-14, 19-22, and 27-33 are pending and examined in the instant Office action.
Even though the claims recite judicial exceptions, the claims are subject matter eligible because the claims recite the practical application of treating subjects with cardiovascular disease.
Withdrawn Rejections
The rejections under 35 U.S.C. 103 and non-statutory double patenting are withdrawn in view of arguments on pages 2-5 of the Remarks.
Claim Rejections - 35 USC § 103
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
The following rejection is newly applied:
Claim(s) 1, 6-8, 11-14, 19-22, and 27-33 is/are rejected under 35 U.S.C. 103 as being unpatentable over Steinhoff et al. [EBioMedicine, volume 22, 29 July 2017, pages 208-224; on IDS] in view of Fortney et al. [PLoS Genetics, volume 11, volume 11, article e1005728, 23 pages; on attached 892 form].
Claim 1 is drawn to a method for treating a subject in need of cardiovascular regeneration for a disease. The method comprises determining the presence in a sample of subject gene as one or more biomarker comprising a mutational variant associated with a positive response to disease therapy to identify a responsive subject. The method comprises administering to the responsive subject the disease therapy wherein the gene is a gene expression mutational variant to a baseline value and/or a reference to a second non diseased subject or individual reference cell without somatic mutation and/or gene expression. for prediction of response to disease therapy, in particular to cardiovascular regeneration. The method requires that the gene be an SH2B3 gene with mutations.
Claim 22 is drawn to a biomarker of the mutant SH2B3 gene in combination with EPC.
Claim 28 is drawn to a kit comprising detection agents for determining the amount of each biomarker.
Claims 29 and 30 are further limiting wherein the prediction is conducted using machine learning.
Claim 31 further limits the disease to comprise myocardial infarction or hear disease.
Claim 32 requires prediction of response to disease therapy.
Claim 33 requires a prediction accuracy of at least 90%.
The document of Steinhoff et al. studies cardiac function improvement and bone marrow response with outcome analysis of the randomized PERFECT Phase III clinical trial of intramyocardial CD 133 positive application after myocardial infarction [title]. Table 4 on page 218 of Steinhoff et al. compares VEGF and EPO (SH3B2 gene biomarkers) responders and non-responders at an initial time and 10 days after treatment. Section 2.10 on pages 214-215 of Steinhoff et al. teaches using machine learning to predict the response of the treatment using cross-validation. Figure 5 and the paragraph bridging columns 1 and 2 on page 221 teaches that a subset of the study has a prediction accuracy of greater than 90%. The Methods section of Steinhoff et al. teaches treating all of the diseased patients, which would include patients responsive to the disease therapy.
While Table 4 of Steinhoff et al. teaches SH2B3 biomarkers, Table 4 of Steinhoff et al. does not teach SH2B3 biomarker variants that are associated with a positive response to disease therapy. Steinhoff does not teach applying machine learning to SH2B3 biomarker variants. However, the paragraph bridging the columns on page 222 of Steinhoff et al. suggests that SNPs in SH2B3 promoter regions relate to coronary heart disease, arteriosclerosis, and human longevity.
The paragraph bridging the columns on page 222 of Steinhoff et al. cites Fortney et al. for further analysis of mutations of SH2B3. The document of Fortney et al. studies that a genome-wide scan informed by age-related disease identifies loci for exceptional human longevity [title]. The first full paragraph on page 13 of Fortney et al. teaches that there are mutants of SH2B3 wherein some mutants of SH2B3 are associated with cardiovascular disease and other mutants are associated with protection against lung and pancreatic cancer, coronary heart disease, rheumatoid arthritis, diastolic blood pressure, bone mineral density and human longevity. The mutants of SH2B3 in the latter aforementioned list (i.e. detected after treatment) are associated with a positive response to disease therapy.
With regard to claim 6, the first paragraph on page 221 of Steinhoff et al. teaches the relation between SH2B3 expression and LNK expression.
With regard to claims 7-8, Table 4 on page 218 of Steinhoff et al. teaches EPC, EPO, and VEGF wherein EPO and VEGF are determined at the protein level.
With regard to claims 11-12, the abstract of Steinhoff teaches stem cell therapy of patients with myocardial infarction (i.e. a heart disease).
With regard to claim 13, Table 4 on page 218 of Steinhoff et al. teaches two time points (i.e. 0 days and 10 days).
With regard to claims 14, 19-21, and 27, the abstract and Section 2 of Steinhoff et al. teaches clinical diagnostic parameters and CD133 positive stem cell therapy and CABG on humans with the assistance of peripheral blood samples.
It would have been obvious to someone of ordinary skill in the art at the time of the effective filing date of the instant application to modify the SH2B3 gene biomarkers of Steinhoff et al. by use of the SH2B3 biomarker variants of Fortney et al. wherein the motivation would have been that Fortney et al. relates SH2B3 variants to outcomes associated with the treatment [first full paragraph, page 13 of Fortney et al.].
It would have been obvious to someone of ordinary skill in the art at the time of the effective filing date of the instant application to modify applying machine learning to the SH2B3 gene biomarkers of Steinhoff et al. by addition of the SH2B3 variants of Fortney et al. because it is obvious to try the machine learning on analogous genes. There would have been a reasonable expectation of success in combining Steinhoff et al. and Fortney et al. because the machine learning mathematical framework of Steinhoff et al. is robust and general applicable to SH2B3, independent of the whether the biomarkers are wild-type or mutant.
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.
The following rejection is newly applied:
Claims 1, 9, 11, 12, 13, 14, 16, 20, and 27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 11, 6, 9, 10, 12, 14, 17, and 8, respectively, of U.S. Patent No. 11,714,093 B2 in view of Fortney et al.
Both sets of claims analogously predict the result of stem cell therapy on humans with heart disease using biomarkers of SH3B2 genes (e.g. VEGF). However, the claims of ‘093 do not teach SH3B2 gene variants.
The document of Fortney et al. studies that a genome-wide scan informed by age-related disease identifies loci for exceptional human longevity [title]. The first full paragraph on page 13 of Fortney et al. teaches that there are mutants of SH2B3 wherein some mutants of SH2B3 are associated with cardiovascular disease and other mutants are associated with protection against lung and pancreatic cancer, coronary heart disease, rheumatoid arthritis, diastolic blood pressure, bone mineral density and human longevity. The mutants of SH2B3 in the latter aforementioned list (i.e. detected after treatment) are associated with a positive response to disease therapy.
While Table 4 of Steinhoff et al. teaches SH3B2 biomarkers, Table 4 of Steinhoff et al. does not teach SH3B2 biomarker variants. However, the paragraph bridging the columns on page 222 of Steinhoff et al. suggests that SNPs in SH3B2 promoter regions relate to coronary heart disease and arteriosclerosis.
It would have been obvious to someone of ordinary skill in the art at the time of the effective filing date of the instant application to modify the SH3B2 gene biomarkers of the claims of ‘093 to include the variant SH2B3 biomarkers of Fortney et al. wherein the motivation would have been that Fortney et al. relates SH2B3 variants to outcomes associated with the treatment [first full paragraph, page 13 of Fortney et al.].
Response to Arguments
Applicant's arguments filed 8 December 2025 have been fully considered but they are not persuasive.
Applicant argues that Steinhoff et al. does not teach SH2B3 variants associated with a positive response to treatment (i.e. pre-operative or post-operative). In response, the claims do not require the SH2B3 variants be pre-operative or post-operative; the claims only require that the SHB3 variants are ASSOCIATED WITH a positive response to treatment. The document of Fortney et al. has been added to demonstrate that are positive mutants of SH2B3 genes associated with increased human longevity and protection from disease. When the claims are given their broadest reasonable interpretation in light of the specification, it is interpreted that these positive mutations (i.e. whether pre-operative or post-operative) are ASSOCIATED WITH a positive response to treatment.
Applicant argues that the machine learning in Steinhoff et al. does not relate the effects of treatment to SH2B3 variants because the machine learning of Steinhoff et al. does not include SH2B3 variants. The document of Fortney et al. has been added to address this argument. There would have been a reasonable expectation of success in combining Steinhoff et al. and Fortney et al. because the machine learning mathematical framework of Steinhoff et al. is robust and general applicable to SH2B3, independent of the whether the biomarkers are wild-type or mutant.
E-mail Communications Authorization
Per updated USPTO Internet usage policies, Applicant and/or applicant’s representative is encouraged to authorize the USPTO examiner to discuss any subject matter concerning the above application via Internet e-mail communications. See MPEP 502.03. To approve such communications, Applicant must provide written authorization for e-mail communication by submitting the following statement via EFS-Web (using PTO/SB/439) or Central Fax (571-273-8300):
Recognizing that Internet communications are not secure, I hereby authorize the USPTO to communicate with the undersigned and practitioners in accordance with 37 CFR 1.33 and 37 CFR 1.34 concerning any subject matter of this application by video conferencing, instant messaging, or electronic mail. I understand that a copy of these communications will be made of record in the application file.
Written authorizations submitted to the Examiner via e-mail are NOT proper. Written authorizations must be submitted via EFS-Web (using PTO/SB/439) or Central Fax (571-273-8300). A paper copy of e-mail correspondence will be placed in the patent application when appropriate. E-mails from the USPTO are for the sole use of the intended recipient, and may contain information subject to the confidentiality requirement set forth in 35 USC § 122. See also MPEP 502.03.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Russell Negin, whose telephone number is (571) 272-1083. This Examiner can normally be reached from Monday through Thursday from 8 am to 3 pm and variable hours on Fridays.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s Supervisor, Larry Riggs, Supervisory Patent Examiner, can be reached at (571) 270-3062.
/RUSSELL S NEGIN/Primary Examiner, Art Unit 1686 7 January 2026