DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendments
Applicant's amendments filed 10/02/2025 to claims 36 and 39 have been entered. Claims 1-35 and 37 are canceled. Claims 51 and 52 have been added. Claims 36 and 38-52 remain pending, and are being considered on their merits. References not included with this Office action can be found in a prior action. Any rejections of record not particularly addressed below are withdrawn in light of the claim amendments and/or applicant’s comments.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 39 and 52 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “about” in claims 39 and 52 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Clarification and/or correction is required.
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.
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.
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.
Claims 36, 38-50, and 52 are rejected under 35 U.S.C. 103 as being unpatentable over Sharma et al. (Circ. Res. (2017), 120, 816-834) in view of Anversa et al. (US 8,512,696) and Kreke et al. (US 2015/0216905; Reference A).
Sharma teaches that human neonatal cardiac progenitor/stem cell (nCPC) total conditioned medium (TCM) (i.e. the secretome) is more effective than control medium (i.e. IMDM) and adult cardiac progenitor/stem cell derived total conditioned medium (aCPC-TCM or aTCM) in recovering cardiac function as measured by ejection fraction, fractional shortening, end systolic volume, and end diastolic volume, and tubular vascularization (Abstract; Fig. 4D-H and J; also see supplemental experimental procedures on p2 for human neonatal cardiac progenitor/stem cell lines), reading in-part on claim 37. Sharma teaches that the nCSC-TCM comprises VEGF-A, HGF, SCF, SDF-1α, IGF-1, bFGF, ANG-1, and PDGF-B and at significantly higher levels as compared to aCPC-TCM (Fig. 2M), reading in-part on claim 37. Sharma teaches that injection of nCSC-TCM into the myocardium of post-myocardial infarction (i.e. post-MI) subjects improves cardiac function as measured by at least about a 15-20% improvement to the (left ventricular) ejection fraction (EF), and at least about a 15-20% improvement to fractional shortening, and reduced the end-systolic volume and end-diastolic volume in comparison to controls (Fig. 4D-G, and the paragraph starting “To determine the contribution…” on p824; ), reading on claim 38, 39, 40-44, and 52. Sharma teaches that annexin V is an early apoptosis marker and is significantly reduced on cardiomyocytes in vitro treated with nTCM as compared to aTCM when the cells are challenged with H2O2 (Fig. 4B and p822, right column, paragraph starting “We next determined the antioxidative effect…)”, reading on claims 47 and 48. Sharma teaches that human microvascular endothelial cells treated in vitro with nCSC-TCM form long and complex mature tube networks (p822, the paragraph starting “To determine whether paracrine…”), reading on claims 49 and 50.
Regarding claim 36, Sharma does not teach the pharmaceutical composition comprising a secretome from immortalized, human, neonatal cardiac stem cells. Regarding claim 36, Sharma does not teach immortalized, human, neonatal cardiac stem cells that are CD117+ (i.e. c-kit+), CD44+, and CD47+
Anversa teaches a population of human cardiac stem cells (hCSCs) comprise immortal DNA, are non-senescent, and have superior regenerative capacity (Col. 3, line 46 through Col. 4, line 3 and Example 8, particularly subheading F starting at Col. 55), reading on claim 37.
Kreke teaches a population of cardiac stem cells that are positive for c-kit (i.e. CD117), CD44, and CD47 (¶0026, ¶0080, and Table 2), reading on claim 36.
Regarding the immortalized cells of claim 36, it would have been obvious to a person of ordinary skill in the art before the invention was filed to further immortalize the neonatal cardiac stem cells of Sharma to produce conditioned medium (i.e. the secretome) in the methods of Sharma in view of Anversa and Kreke. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because Sharma and Anversa are both directed towards cardiac stem cells and because Kreke teaches that c-kit/CD117, CD44, and CD47 are all known cell markers indicative of cardiac stem cells. The skilled artisan would have been motivated to do so because Anversa teaches that the immortalized human cardiac stem cells are non-senescent and so would retain the ability to divide and proliferate and therefore would improve upon the methods of Sharma as non-senescent cells would further divide and proliferate in vitro to generate the therapeutic conditioned medium to treat the subjects of Sharma.
Regarding claims 45 and 46, a whereby/wherein clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited. See M.P.E.P. § 2111.04. In this case, each of claims 41, 43-47, 49, and 50 recites a wherein clause that is only expressing the intended result of the process steps of claim 36, and claim 36 is prima facie obvious over the combination of Sharma, Anversa, and Kreke as set forth above. Therefore and absent any showing to the contrary, the teachings of Sharma, Anversa, and Kreke inherently read on the outcome of claims 45 and 46
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claim 51 is rejected under 35 U.S.C. 103 as being unpatentable over Sharma, Anversa, and Kreke as applied to claim 36 above, and further in view of Kaushal et al. (US 2015/0328263; Reference B).
The teachings of Sharma, Anversa, and Kreke are relied upon as set forth above. Kreke further teaches a population of cardiac stem cells that are positive for CD73, CD90, and CD105 and negative for CD45 (¶0026 and ¶0080), reading in-part on claim 51
Regarding claim 51, Sharma, Anversa, and Kreke do not teach immortalized, human, neonatal cardiac stem cells that are further negative for CD31, CD34, and tryptase.
Kaushal teaches a population of cardiac stem cells that are positive for c-kit/CD117, CD90, and CD105 and negative for CD31, CD34, CD45, and tryptase (claim 1), reading on claim 51.
Regarding the immortalized cells of claim 37, it would have been obvious to a person of ordinary skill in the art before the invention was filed to further immortalize the neonatal cardiac stem cells of Sharma to produce conditioned medium (i.e. the secretome) in the methods of Sharma in view of Anversa, Kreke, and Kaushal. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because Sharma and Anversa are both directed towards cardiac stem cells and because Kreke and Kaushal teaches CD73+, CD90+, CD105+, CD31-, CD34-, CD45-, and tryptase- are collectively indicative of cardiac stem cell fate. The skilled artisan would have been motivated to do so because Anversa teaches that the immortalized human cardiac stem cells are non-senescent and so would retain the ability to divide and proliferate and therefore would improve upon the methods of Sharma as non-senescent cells would further divide and proliferate in vitro to generate the therapeutic conditioned medium to treat the subjects of Sharma.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Response to Arguments
Applicant's arguments on pages 4-10 of the reply have been fully considered, but not found persuasive of error for the reasons given below.
On pages 7-10 of the reply, Applicant alleges that immortalization of cardiac stem cells produces an unexpected result in the subsequent secretome/conditioned medium produced by said immortalized cardiac stem cells. This is not persuasive because 1) Applicant is relying on unclaimed features (i.e., HGF concentration, and more generally growth factor concentrations) which are not recited in the rejected claim(s); although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993), and 2) the claims are directed towards methods of modulating cardiac function in subject(s) in need thereof, and at this time there is no evidence of record that the claimed secretome/conditioned medium made from immortalized, human, neonatal cardiac stem cells otherwise yield an unexpected outcome as compared to the that human neonatal cardiac progenitor/stem cell (nCPC) total conditioned medium (TCM) (i.e. the secretome) of Sharma. See M.P.E.P. § 716 for general guidance on presenting objective evidence of nonobviousness and should be reasonable commensurate to the scope of the claims (see M.P.E.P. § 716.02(d)).
Conclusion
No claims are allowed. No claims are free of the art.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN C BARRON whose telephone number is (571)270-5111. The examiner can normally be reached 7:00am-3:30pm EDT/EST (M-F).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached at 571-272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Sean C. Barron/Primary Examiner, Art Unit 1653