DETAILED ACTION
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 .
Status of Application/Claims
Applicant’s response filed on 6/30/2026 has been considered. The declaration submitted by Dr. Tsunao Kishida on 6/30/2026 was received and fully considered. Briefly, the declaration argues that the induction of brown adipocytes does not require a TGF-β pathway inhibitor with a particular chemical structure, rather that the compound is capable of providing such activity.
Claims 19-20 have been canceled. Claim 16 has been amended. Claims 16-18 are pending and are examined in the present Office Action. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Priority
Applicant’s claim for the benefit of a prior-filed application JP 2015-207529, 371 of PCT/JP2016/081187 and DIV of 15/769,595 filed on 10/21/2015, 10/20/2016 and 9/17/2018, respectively, under 35 U.S.C 119(e) or under 35 U.S.C 120, 121 or 365(c) is acknowledged.
Accordingly, the effective priority date of the instant application is granted as 10/21/2015.
Withdrawn and Maintained Rejections
The 35 U.S.C. 112(a) enablement rejection of claims 16-18 and 20 is withdrawn in light of applicants claim amendments moving the limitations of claim 19 into independent claim 16.
The 35 U.S.C. 112(a) written description rejection of claims 16 and 19-20 is withdrawn in light of applicants arguments and declaration submitted by Dr. Tsunao Kishida on 6/30/2026 which argued that the induction of brown adipocytes does not require a TGF-β pathway inhibitor with a particular chemical structure, rather that the compound is capable of providing such activity.
The 35 U.S.C. 103 rejection of claims 16-18 over Kishida et al. WO 2014/010746, publication date 1/16/2014 in view of Hebrok et al. US20180216076 has been applied in modified form to address applicants claim amendments to independent claim 16.
The nonstatutory double patenting rejections of claims 16-19 over claims 1-9 of US Patent No. 11,459,546 and claims 10-21 of copending Application No: 18/517,402 have been withdrawn and re-applied in modified form to address applicants claim amendments to independent claim 16.
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 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.
Claims 16-18 are rejected in modified form under 35 U.S.C. 103 as being unpatentable over Kishida et al. WO 2014/010746, publication date 1/16/2014 (hereinafter Kishida, reference of record) in view of Hebrok et al. US20180216076, published 8/2/2018, priority date 7/27/2015 (hereinafter Hebrok, reference of record). This rejection is applied in modified form to address applicants claim amendments on 6/30/2026. A reply to applicants’ traversal is found below.
Claim 16: Kishida describes a method for generating brown adipocytes comprising converting fibroblasts (somatic cells) in a differentiation induction medium comprising insulin, IBMX, dexamethasone, idomethacine, T3 and rosiglitazone (Kishida, intro). Kishida states that Sox2 is an important brown adipocyte related gene which can be induced to obtain brown adipocytes from somatic cells (Kishida, para 66-67 and 71). Kishida describes the use of rosiglitazone, which is a known PPAR-γ agonist (Kishida, example 1). Kishida states that brown adipocytes can be directly induced from somatic cells, without passing through iPS cells, which avoids problems attributed to oncogenesis (Kishida, para 94).
Kishida does not describe culturing brown adipocytes in the presence of a TGF-β pathway inhibitor.
Claims 16-18: Hebrok describes a method for converting pancreatic endothermal progenitor cells (a type of somatic cell) to pancreatic beta-like cells (another type of somatic cell) by contacting the cells with a TGF-β pathway inhibitor, with specific reference to an Alk5 inhibitor II (Hebrok, para 26, 61, 252). Hebrok describes Alk5 inhibitor II as a selective and ATP-competitive inhibitor of the TGF-β family type 1 receptor activating receptor-like kinase (ALK5) that can replace Sox2 when reprogramming cells (Hebrok, para 252).
It would have been obvious to one of ordinary skill in the art to use an Alk5 inhibitor II as described by Hebrok to facilitate the direct conversion of fibroblasts into brown adipocytes in the methods for direct conversion described by Kishida. It would have been a matter of combining prior art elements according to known methods to yield predictable results since both authors are concerned with the direct conversion of somatic cells. Hebrok expressly states that Alk5 inhibitor II acts a selective and ATP-competitive inhibitor of the TGF-β family type 1 receptor activating receptor-like kinase (ALK5) that can replace Sox2 when reprogramming cells (Hebrok, para 252). Kishida found that Sox2 is an important brown adipocyte-related gene which can be induced to obtain brown adipocytes from somatic cells (Kishida, para 66-67 and 71). Thus, one of ordinary skill would have motivation to include Alk5 inhibitor II into the methods of Kishida given its role as a replacement for Sox2. One would have a reasonable expectation of success in using Alk5 inhibitor II for the direct conversion of fibroblasts into brown adipocytes given the well understood mechanisms of action of Alk5 on the TGF-β pathway and Sox2. Accordingly, in the absence of evidence to the contrary, one of ordinary skill in the art would have considered the claimed invention to have been prima facie obvious to at the time the invention was made.
Reply to Applicant’s Traversal
Applicant argues that Hebrok shows that Alk5 inhibitor II can be used in place of Sox2 when reprogramming iPS cells and does not relate to the direct conversion from one somatic cell type to a brown adipocyte. Applicant points to the new claim amendments in claim 16, describing that the conversion takes place without converting into a pluripotent stem cell.
These arguments have been fully considered, but are not found persuasive since Kishida (the primary reference) fully acknowledges that brown adipocytes can be directly induced from somatic cells, without passing through iPS cells, which avoids problems attributed to oncogenesis (Kishida, para 94). One would have a reasonable expectation of success in using Alk5 inhibitor II for the direct conversion of fibroblasts into brown adipocytes given the well understood mechanisms of action of Alk5 on the TGF-β pathway and Sox2. Accordingly, in the absence of evidence to the contrary, one of ordinary skill in the art would have considered the claimed invention to have been prima facie obvious to at the time the invention was made.
Nonstatutory 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 Langi, 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 706.02(1)(1) - 706.02(1)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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 autoprocessed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 16-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of US Patent No. 11,459,546 in view of Kishida (supra). Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims would make obvious the instant claims if they were available as prior art. This rejection is newly applied to address applicants claim amendments on 6/30/2026.
The patented claims are drawn to a method for producing brown adipocytes comprising culturing fibroblasts in the presence of an ALK5 inhibitor. The patented claims describe conversion without introducing a gene or conversion to an iPS. The patented claims do not describe a medium comprising a PPAR-γ agonist.
However, Kishida describes a method for generating brown adipocytes comprising converting fibroblasts (somatic cells) in a differentiation induction medium comprising insulin, IBMX, dexamethasone, idomethacine, T3 and rosiglitazone (Kishida, intro). Kishida describes the benifitial use of rosiglitazone, which is a known PPAR-γ agonist (Kishida, example 1). PPAR-γ agonist serves as the main genetic switch required to create any fat cell and can accelerate fat generation (Kishida, example 1). Kishida states that brown adipocytes can be directly induced from somatic cells, without passing through iPS cells, which avoids problems attributed to oncogenesis (Kishida, para 94).
Thus, the patented claims would make obvious the instantly claimed invention, which is drawn to a similar method for generating brown adipocytes comprising culturing fibroblasts in the presence of a TGF-β inhibitor like an ALK5 inhibitor and a PPAR-γ agonist. The claim sets are patentable indistinct therefore.
Claims 16-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 10-21 of copending Application No: 18/517,402 in view of Kishida (supra). Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims would make obvious the instant claims if they were available as prior art. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. This rejection is newly applied to address applicants claim amendments on 6/30/2026.
The competing claims are drawn to a method for generating a brown adipocyte comprising culturing a fibroblast in the presence of a TGF-β inhibitor comprising ALK-5 inhibitor II. The competing claims describe conversion without introducing a gene or conversion to an iPS. The competing claims do not describe a medium comprising a PPAR-γ agonist.
However, Kishida describes a method for generating brown adipocytes comprising converting fibroblasts (somatic cells) in a differentiation induction medium comprising insulin, IBMX, dexamethasone, idomethacine, T3 and rosiglitazone (Kishida, intro). Kishida describes the benifitial use of rosiglitazone, which is a known PPAR-γ agonist (Kishida, example 1). PPAR-γ agonist serves as the main genetic switch required to create any fat cell and can accelerate fat generation (Kishida, example 1). Kishida states that brown adipocytes can be directly induced from somatic cells, without passing through iPS cells, which avoids problems attributed to oncogenesis (Kishida, para 94).
Thus, the competing claims would make obvious the instantly claimed invention, which is drawn to a similar method for generating brown adipocytes comprising culturing fibroblasts in the presence of a TGF-β inhibitor like an ALK5 inhibitor and a PPAR-γ agonist. The claim sets are patentable indistinct therefore.
Conclusion
No claims allowed.
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 extension fee 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.
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Alexander Nicol
Patent Examiner
Art Unit 1634
/ALEXANDER W NICOL/Examiner, Art Unit 1634
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699
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