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 .
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 27 July, 2026 has been entered.
Claims 1-2, 5, and 12-15 were previously pending.
Applicant previously elected without traverse of the invention of group I (claims 1-6) in the reply filed on 09 June, 2025 and the restriction requirement issued 08 April, 2025, was still deemed proper and made FINAL.
Receipt is acknowledged of the amendments to the claims filed 27 July, 2026. Claims 1 and 5 are amended. Claims 16-18 are newly added.
Claims 12-15 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Therefore, claims 1, 2, 5, and 16-18 are pending and under examination in the present Official Action.
Claim Objections
The objection to claims 12-15 for not being properly labeled as withdrawn is withdrawn in view of Applicant’s latest submission which does properly label the claims.
The objection to claim 5 for not properly capitalizing proper nouns is withdrawn in view of Applicant’s latest submission which does properly capitalize the proper nouns.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/JP2020/042898, filed 18 November, 2020, which claims priority to Japan Application No. JP2019-211990, filed 25 November, 2019. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). Acknowledgement is made of applicant’s filing of certified untranslated copies of papers required by 37 CFR 1.55 in this application on 25 May, 2022.
The earliest possible priority for the instant application is 25 November, 2019.
Withdrawn Rejections/Objections in view of Applicant’s Amendments/Arguments
Claim Rejections - 35 USC § 112- First paragraph- New Matter
The rejection of claims 1, 2, and 5 under 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement is withdrawn in view of Applicant’s amendments to the claims. Applicant has amended claim 1 to remove the language “without generating a pluripotent stem cell from the fibroblast”.
It is noted that Applicant has added new claim 17 which presents substantially the same issue as was presented by the cancelled language of claim 1. However, upon further consideration, the language of claim 17 does not appear to be new matter. The language presents a negative proviso which is supported by the original disclosure’s affirmative recitation of pluripotent stem cells as one option for the practice of the invention. See MPEP 2173.05(i). See also, [0029] of the published application.
Claim Rejections - 35 USC § 103
The rejection of claims 1-2, and 5 under 35 U.S.C. 103 as being unpatentable over Takeda et al. (Scientific reports 7.1 (2017): 4304., hereinafter “Takeda”, of record) in view of Totonchi et al. (International Journal of Developmental Biology 54.5 (2010)., hereinafter “Totonchi”, of record), and Tseng et al. (Nature 454.7207 (2008): 1000-1004., hereinafter “Tseng”, of record) is withdrawn in view of Applicant’s arguments against Totonchi in favor of the new rejection under 35 U.S.C. 103 presented below. Although Totonchi teaches the advantages of using a serum-free culture medium, the thrust of Totonchi is directed towards genetic induction of iPSCs. The Examiner believes prosecution will be better served by providing a more specific teaching for why a person having ordinary skill in the art would be motivated to use a serum-free medium.
Maintained Rejections in view of Applicant’s Amendments/Arguments
Provisional Double Patenting
Claims 1-2, and 5 remain provisionally rejected and new claims 16-18 are newly provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8-12 of copending Application No. 18/692,497 (reference application) in view of Takeda et al. (Scientific reports 7.1 (2017): 4304., hereinafter “Takeda”, of record), and Tseng et al. (Nature 454.7207 (2008): 1000-1004., hereinafter “Tseng”, of record). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims 8-12 are related to the instant claims 1-2, 5, and 16-18 as species-genus and claims 1-2, 5, and 16-18 are obvious over the reference claims in view of Takeda.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Reference claim 8 claims “A method of producing low-molecular-weight compound-induced brown adipocytes by inducing differentiation directly from a somatic cell using a compound targeting a cell membrane receptor and having a browning-promoting effect on brown adipocytes, wherein the method comprises a step of culturing a somatic cell in a serum-free differentiation induction medium in which the compound, a selective PPARγ agonist, and a cAMP inducer are present.” This claim is a species of the genus of methods claimed in instant claim 1. It is well established that a species of a claimed invention renders the genus obvious. In re Schaumann , 572 F.2d 312, 197 USPQ 5 (CCPA 1978).
Dependent claim limitations found in instant claims 2, and 5 can be found throughout reference claims 9-12.
Insofar as claim 1 is a species of the reference claims as it requires the medium to be absent of an ALK2/3 inhibitor, an ALK5 inhibitor, and an ALK6 inhibitor, Takeda teaches these claim limitations and provides motivation to select such a medium. Insofar as claim 18 requires BMP7 to be in the range of 1-50ng/mL, Tseng teaches a similar concentration for BMP7 in a culture medium. Therefore, instant claims 1-2, 5, and 16-18 would have been prima facie obvious to a person having ordinary skill in the art in view of the reference claims and Takeda.
New Rejections
Claim Rejections - 35 USC § 103
Claims 1-2, 5, and 16-18 are rejected under 35 U.S.C. 103 as being unpatentable over Takeda et al. (Scientific reports 7.1 (2017): 4304., hereinafter “Takeda”, of record) in view of Karnieli, et al. Cytotherapy 19.2 (2017): 155-169, hereinafter “Karnieli”, Tseng et al. (Nature 454.7207 (2008): 1000-1004., hereinafter “Tseng”, of record), and BMP7 Product Specifications, R&D Systems, https://www.rndsystems.com/products/recombinant-human-bmp-7-protein_354-bp#product-specifications, Accessed: 12 August, 2026.
Takeda discloses a method for direct conversion of fibrobasts to brown adipocyte-like cells comprising culturing the fibroblasts in DMEM supplemented with rosiglitazone and forskolin (Takeda, page 9, second and third full paragraphs). Takeda teaches that Rosiglitazone is a PPARγ agonist (Takeda, Abstract) and that Forskolin is a cAMP inducer (Takeda, page 2, first full paragraph). Takeda also teaches that their chemical induction method avoids undesired effects from gene induction procedures for generating iPSCs (Takeda, Abstract). Thus, Takeda teaches a method of inducing fibroblasts into brown adipocytes via chemical induction as an alternative to genetic induction medium methods. Takeda teaches various chemical cocktails for culturing the fibroblasts into brown adipocytes (Takeda, Table 2). All of the possible media contained Rosiglitazone and some contained Forskolin (F), SB-431542 (S), LDN-193189 (L), and/or Dorsomorphin (D) (Takeda, page 2, “Results” heading, first two paragraphs; Table 2). Takeda teaches 2 combinations which comprise Rosiglitazone and Forskolin and which do not comprise either S, L, or D alone or in combination and which efficiently convert fibroblasts into brown adipocytes (Takeda, Table 2) (see below).
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Note that the instant specification teaches that SB431542 is an ALK5 inhibitor, LDN193189 is an ALK2/3 inhibitor, and that Dorsomorphin is an ALK2/3/6 inhibitor (Instant specification, [0003]). Thus, Takeda teaches 2 media for culturing fibroblasts to produce brown adipocytes which comprise both Rosiglitazone and Forskolin and which do not comprise an ALK5 inhibitor, an ALK2/3 inhibitor, or an ALK6 inhibitor.
It is noted that Takeda teaches each of those 2 media facilitate conversion of fibroblasts into brown adipocytes with varying levels of efficiency (Takeda, Table 2).
Takeda does not teach the use of a serum-free base medium as required by instant claim 1.
Karnieli teaches that serum quality varies from batch to batch which affects reproducibility, presents a risk of contamination, and raises ethical issues (Karnieli, page 167, “Summary”). Karnieli teaches that there is a great need for serum-free alternatives in cell culture methods (Karnieli, Abstract; page 167, “Summary”). Karnieli concludes with a recommendation to consider using serum-free media in new product development as early as possible to save time and significant resources that would be required to convert a product to a serum-free method in clinical trials down the line (Karnieli, page 167, “Summary”). While Karnieli acknowledges that growth media have a great influence on cell characteristics and that there are differences and challenges posed by particular cell products, these considerations would be a matter of routine experimentation to a person having ordinary skill in the art. Thus, A person having ordinary skill in the art, when developing cell therapy products, would have been motivated to use a serum free base medium to improve reproducibility, remove contamination risks, and avoid ethical concerns associated with serum, and they would have been motivated to do so as early as possible in the development stage to save significant time and resources as recommended by Karnieli directly.
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have substituted a serum-free medium as taught by Karieli for the base medium of Takeda and arrive at the invention claimed in instant claim 1 with a reasonable expectation of success because they would have been motivated to do so to improve reproducibility, remove contamination risks, and avoid ethical concerns associated with serum, and they would have been motivated to do so as early as possible in the development stage to save significant time and resources as recommended by Karnieli directly. A person having ordinary skill in the art would have had a reasonable expectation of success in using a serum-free medium as the base medium for the method of Takeda insofar as they would have reasonably expected to be able to gain the same advantages taught by Karnieli while still accomplishing direct conversion as taught in Takeda through routine experimentation.
Regarding claim 2, the combination of Takeda and Karnieli does not teach or suggest adding BMP7 to the medium.
Tseng teaches that while some members of the family of bone morphogenic proteins (BMP) support white adipocyte differentiation, BMP7 singularly promotes differentiation of brown preadipocytes (Tseng, Abstract). Tseng also teaches that BMP7 activates a full program of brown adipogenesis including increasing expression of the adipogenic transcription factor PPARγ among others (Tseng, Abstract). Tseng also teaches that BMP7 triggers commitment of mesenchymal progenitor cells to a brown adipocyte lineage (Tseng, Abstract). Tseng also teaches adding BMP7 to a medium (Tseng, “METHODS” heading, first two paragraphs).
Therefore, upon viewing the teachings of Takeda, Karnieli, and Tseng, it would have been prima facie obvious to a person having ordinary skill in the art to have added BMP7 as taught by Tseng to the medium taught by Takeda and Karnieli and to have arrived at the invention claimed in instant claim 2 with a reasonable expectation of success because they would have been motivated to do so to more selectively drive differentiation towards the brown adipocyte lineage as taught by Tseng.
Regarding instant claims 5 and 16, Takeda teaches both Rosiglitazone and Forskolin.
Regarding claim 17, the method of Takeda is a direct conversion method which allows for differentiation without going through a pluripotent state (Takeda, page 1, first paragraph).
Regarding claim 18, the BMP7 of Tseng is added at to medium at a range of 3.3-8.3nM (Tseng, page 1004, first partial paragraph). The BMP7 of Tseng was purchased from R&D Systems which lists rhBMP7 at a molecular weight of 15,700g/mol (See R&D Systems, whole document). 3.3-8.3nM correlates with a concentration range of 51.8-130.31ng/mL for BMP7 assuming a molecular weight of 15,700g/mol. It is noted that, "where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II)(A). Tseng discloses the general conditions for BMP7 concentration in a medium for differentiating adipocytes.
Response to Arguments
Applicant argues against Takeda, alleging that a person having ordinary skill in the art would have no reasonable expectation of success because the media combinations taught in Takeda which contain Rosiglitazone and Forskolin without the ALK inhibitors were outperformed by other taught combinations as denoted by the relatively fewer +’s in Table 2 of Takeda. This argument has been fully considered but has not been found persuasive for the following reasons.
Denoting the MF media with a ++ where other combinations were denoted with a ++++ in Table 2 of Takeda does not remove any reasonable expectation of success because obviousness does not require absolute predictability, only a reasonable expectation of success, i.e., a reasonable expectation of obtaining similar properties. See, e.g., In re O’Farrell, 853 F.2d 894, 903, 7 USPQ2d 1673, 1681 (Fed. Cir. 1988). Here, upon viewing Table 2 of Takeda, a person having ordinary skill in the art would have a reasonable expectation of obtaining similar properties insofar as they would reasonably expect to be able to directly convert a fibroblast into a brown adipocyte with Rosiglitazone and Forskolin without any ALK inhibitors. Further, “[a] known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use.” In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994). In denoting the MF combination with a ++ rather that a ++++, Takeda has not rendered the MF condition nonobvious by removing any reasonable expectation of success for a person having ordinary skill in the art following in Takeda’s footsteps. Accordingly, the arguments have been fully considered but have not been found persuasive.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRENDAN THOMAS TINSLEY whose telephone number is (703)756-5906. The examiner can normally be reached Mon-Fri 8:00-5:00.
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/BRENDAN THOMAS TINSLEY/Examiner, Art Unit 1634
/MARIA MARVICH/Primary Examiner, Art Unit 1634
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