DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, 18092495, (US PG-Publication 20230220332), filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1 and 3-20 are pending and examined.
Priority
The filing receipt, mailed 6/6/2023, states that the domestic Priority data as claimed by applicant states that this application is a CON of PCT/IL2021/050817, filed 07/01/2021, which claims benefit of 63/047,375, filed 07/02/2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 12/8/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Interpretation
Amended independent claim 1 et seq, filed 12/8/2025, does not provide a limiting definition of “adipogenic differentiation agent(s).” The instant Specification at p. 26, lines 27-30, states “[a]s used herein the phrase ‘adipogenic differentiation agent’ refers to a substance e.g., hormone and/or a chemical agent which when added to pluripotent stem cells in an in-vitro culture results in induction of differentiation of the cells towards the adipogenic cell lineage, ultimately resulting in the generation of adipocytes.”
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.
1. Claim(s) 1, 3-18, is/are rejected under 35 U.S.C. 103 as being unpatentable over Amit, US 9,206,392, (Amit ‘392), Saeki, US 20210177909, Serial No. 17268190, Amit and Angel, US 2019/0284526, (of record, IDS) and Amit and Itskovitz-Eldor, US 10,597635, (of record, IDS).
Amit, US 9,206,392, throughout the patent and abstract, discloses a method of generating a primate embryonic cell culture/ cell line comprising providing a blastocyst of at least nine days post fertilization, isolating cells from the blastocyst, and culturing the isolated cells, thereby generating the primate extraembryonic cell culture or embryonic cell lime (col. 3, lines 18-24). Amit ‘392 teaches that the providing the blastocyst is effected by ex-vivo culturing the blastocyst (col. 3, lines 62-64). Amit ‘392 also teaches that the isolated embryonic cell being capable of differentiating to derivatives of each of an endoderm, mesoderm, and ectoderm tissues ((col. 3, lines 7-11), (col. 9, lines 10-24)) which derived from epiblast cells and that the blastocysts are then cultured as whole embryos for at least nine and no more than fourteen days post fertilization (col. 10, lines 1-6). It is noted that the instant Specification, as filed, does not appear to provide a limiting definition for livestock.
Amit ‘392 states, throughout the patent: at col. 4, lines 54-57, that their isolated primate embryonic cell can be passaged at least 100 times, as in claim 4; feeder-free solid surface cultures, col. 24, lines 14-30, culture dishes, reading on two dimensional culture systems; at col. 11, lines 60-67, as in claims 5, 6, 7; culture medium comprising FBS, at col. 22, lines 10-26, as in claim 7; at col. 14, lines 44-67, teach bFGF, as in claim 9; at col. 10, lines 21-67, teaches culturing ES cells in medium containing serum or leukemia inhibitor factor (LIF) and bFGF, reading on claim 10.
Amit ‘392 does not describe production of spontaneous adipocytes from stem cells, in medium with or without dexamethasone, containing IL6IL6 chimera. Amit ‘392 does not describe obtaining a population of mammalian livestock pluripotent stem cells[[,]] capable of spontaneous differentiation into adipocytes in an absence of adipogenic differentiation agent(s) thereby deriving the mammalian livestock pluripotent stem cells line.
Saeki, discloses throughout the publication and abstract, and at para [0060]-[0063], brown adipocytes free of contact with heterologous cells or exogenous cytokines. Saeki states:
[0060] In addition, in the process of carrying out the above experiment to generate brown adipocytes using pluripotent stem cells cultured in a feeder-free culture system, the present inventors surprisingly discovered that, in pluripotent stem cells cultured with a feeder-free system, it was possible to spontaneously differentiate brown adipocytes just by forming spheres through a suspension culture (where the spheres are formed after pluripotent stem cells are dispersed into single cells and suspension cultured using a medium for producing cell aggregates comprising no cytokine cocktail) without adding a cytokine cocktail that was conventionally added to generate brown adipocytes, and then culturing the obtained sphere cells in a brown adipocyte induction medium comprising no cytokine cocktail (FIG. 7).
Saeki, at para 60, (emphasis added). Saeki at Figure 7, present induction of brown adipocyte proteins without cytokine cocktail. Saeki, at para [0125], [0160]-[0164], discuss culturing for e.g., 8-10 days, for (Saeki at para [0161].
Saeki, e.g., states :
[0220] Since brown adipocytes generated from feeder-free system-derived pluripotent stem cells produced in this manner are not in contact with heterologous cells such as feeder cells or exogenous cytokines during the generation process, they are extremely high-quality brown adipocytes that are not contaminated with or influenced by heterologous cells or exogenous cytokines. By preparing a supernatant using these brown adipocytes, it is possible to obtain a high-quality brown adipocyte supernatant that also does not comprise any factors derived from heterologous cells or exogenous contaminants.
Saeki at para [0220], (emphasis added).
Amit and Angel, US 2019/0284526, (of record, IDS), teach throughout the publication and abstract, and e.g., at p. 1, para [0009]-[0011] teaches WNT3A polypeptide, as in claim 10; at para [0038], [0218]-[0221], teach IL6PIL6 chimera, as in claim 8; at [0213]-[0216].
Amit and Itskovitz-Eldor, US 10,597635, (of record, IDS), Serial No. 15403303, at col. 28, line-col. 30, line 33, teach IL6IL6 chimera and bFGF, and their use together in medium, as in claim 11; at col. 36, lines 57-col. 37, line 16, discloses that extracellular matrix, as in claim 12, can add cell attachment to cells, to provide a suitable culture substrate.
It would have been prima facie obvious before the effective filing date of the instant application, for one of ordinary skill in the art to have made and used methods for obtaining a population of mammalian livestock pluripotent stem cells, as described by Amit ‘392, with the spontaneous differentiation into adipocytes in an absence of adipogenic differentiation agent(s) thereby deriving the mammalian livestock pluripotent stem cells line. It would have been prima facie obvious before the effective filing date of the instant application, for one of ordinary skill in the art to have made and used medium comprising bFGF, WNT3A polypeptide, IL6PIL6 chimera, IL6IL6 chimera and bFGF, and addition of extracellular matrix droplets to embryos prior to culturing, as taught by Amit’392 and Angel and Amit and Itskovitz-Eldor.
One of ordinary skill in the art would have been motivated to have combined these components, as taught by Amit’392, Saeki, Amit and Angel, and Amit and Itskovitz-Eldor, because these components are taught by the art for supporting and culturing embryo cultures.
One of ordinary skill in the art would have been motivated to have combined derived spontaneously-differentiated adipocytes in order to obtain extremely high-quality brown adipocytes that are not contaminated with or influenced by heterologous cells or exogenous cytokines the medium for culturing the embryos, as taught by Saeki.
2. Claim(s) 19-20, is/are rejected under 35 U.S.C. 103 as being unpatentable over Amit, US 9,206,392, (Amit ‘392), Saeki, US 20210177909, Serial No. 17268190, Amit and Angel, US 2019/0284526, (of record, IDS) and Amit and Itskovitz-Eldor, US 10,597635, (of record, IDS), as applied to claims 1, 2-18, above, and further in view of Ben-Arye, June 2019, Frontiers in Sustainable Food Systems, Vol 3, pages 1 to 19).
The prior art references of Amit, US 9,206,392, (Amit ‘392), Saeki, US 20210177909, Serial No. 17268190, Amit and Angel, US 2019/0284526, (of record, IDS) and Amit and Itskovitz-Eldor, US 10,597635, (of record, IDS), are relied upon as forth in the above prior art rejection.
Amit, US 9,206,392, (Amit ‘392), Saeki, US 20210177909, Serial No. 17268190, Amit and Angel, US 2019/0284526, (of record, IDS) and Amit and Itskovitz-Eldor, US 10,597635, (of record, IDS), Amit ‘287 does not describe production of spontaneous adipocytes for incorporation into food products.
Saeki, 20210177909, discloses throughout the publication and abstract, and at para [0060], [0075]-[0083], [0085], [0172], [0178], [0192]-[0209], [0299]-[0302], a method of obtaining stem cells to thereby obtain a population of mammalian livestock pluripotent stem cells capable of spontaneous differentiation into adipocytes in an absence of adipogenic differentiation agent(s) thereby deriving the mammalian livestock pluripotent stem cells line.
Saeki, discloses throughout the publication and abstract, and at para [0060]:
[0060] In addition, in the process of carrying out the above experiment to generate brown adipocytes using pluripotent stem cells cultured in a feeder-free culture system, the present inventors surprisingly discovered that, in pluripotent stem cells cultured with a feeder-free system, it was possible to spontaneously differentiate brown adipocytes just by forming spheres through a suspension culture (where the spheres are formed after pluripotent stem cells are dispersed into single cells and suspension cultured using a medium for producing cell aggregates comprising no cytokine cocktail) without adding a cytokine cocktail that was conventionally added to generate brown adipocytes, and then culturing the obtained sphere cells in a brown adipocyte induction medium comprising no cytokine cocktail (FIG. 7).
Saeki at para [0060].
Amit ‘287 is relied upon, as above. Amit ‘287 does not describe production of spontaneous adipocytes from stem cells, in medium with or without dexamethasone, containing IL6IL6 chimera, and food products incorporating from the adipocytes so produced.
Amit and Itskovitz-Eldor, US 10,597635, (of record, IDS), Serial No. 15403303, at col. 28, line-col. 30, line 33, teach IL6IL6 chimera and bFGF, and their use together in medium.
Ben-Arye, June 2019, Frontiers in Sustainable Food Systems, Vol 3, pages 1 to 19, throughout the publication and abstract, and e.g., at pp. 2-4, teach adipocyte production from stem cells to produce intramuscular fat (IMF), at pp. 6-7, noting that IMF have a crucial role in meat quality and taste.
It would have been prima facie obvious before the effective filing date of the instant application, for one of ordinary skill in the art to have made and used spontaneous adipocytes from stem cells, in medium with or without dexamethasone, containing IL6IL6 chimera, and food products incorporating from the adipocytes so produced.
One of ordinary skill in the art would have been motivated to have made and used spontaneous adipocytes from stem cells, in creating cultivated meat, using medium with or without dexamethasone, containing IL6IL6 chimera, to produce food products incorporating from the adipocytes so produced, because fat would enhance the taste of cultivated meat.
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.
Claim 1, 3-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7 and 8 of Amit, U.S. Patent No. 8,354,277, Saeki, US 20210177909, Serial No. 17268190, Amit and Angel, US 2019/0284526, (of record, IDS) and Amit and Itskovitz-Eldor, US 10,597635, (of record, IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because Amit ‘277, recites in the claims pre-implantation stage blastocysts are cultured ex vivo for at least nine to fourteen days post fertilization to produce a pre-gastrulation, extended blastocyst.
Amit , U.S. Patent No. 8,354,277, does not claim production of spontaneous adipocytes from stem cells, in medium with or without dexamethasone, containing IL6IL6 chimera. Amit ‘392 does not describe obtaining a population of mammalian livestock pluripotent stem cells, capable of spontaneous differentiation into adipocytes in an absence of adipogenic differentiation agent(s) thereby deriving the mammalian livestock pluripotent stem cells line.
Saeki, discloses throughout the publication and abstract, and at para [0060]-[0063], brown adipocytes free of contact with heterologous cells or exogenous cytokines. Saeki states:
[0060] In addition, in the process of carrying out the above experiment to generate brown adipocytes using pluripotent stem cells cultured in a feeder-free culture system, the present inventors surprisingly discovered that, in pluripotent stem cells cultured with a feeder-free system, it was possible to spontaneously differentiate brown adipocytes just by forming spheres through a suspension culture (where the spheres are formed after pluripotent stem cells are dispersed into single cells and suspension cultured using a medium for producing cell aggregates comprising no cytokine cocktail) without adding a cytokine cocktail that was conventionally added to generate brown adipocytes, and then culturing the obtained sphere cells in a brown adipocyte induction medium comprising no cytokine cocktail (FIG. 7).
Saeki, at para 60, (emphasis added). Saeki at Figure 7, present induction of brown adipocyte proteins without cytokine cocktail. Saeki, at para [0125], [0160]-[0164], discuss culturing for e.g., 8-10 days, for (Saeki at para [0161].
Saeki, e.g., states :
[0220] Since brown adipocytes generated from feeder-free system-derived pluripotent stem cells produced in this manner are not in contact with heterologous cells such as feeder cells or exogenous cytokines during the generation process, they are extremely high-quality brown adipocytes that are not contaminated with or influenced by heterologous cells or exogenous cytokines. By preparing a supernatant using these brown adipocytes, it is possible to obtain a high-quality brown adipocyte supernatant that also does not comprise any factors derived from heterologous cells or exogenous contaminants.
Saeki at para [0220], (emphasis added).
Amit and Angel, US 2019/0284526, (of record, IDS), teach throughout the publication and abstract, and e.g., at p. 1, para [0009]-[0011] teaches WNT3A polypeptide, as in claim 10; at para [0038], [0218]-[0221], teach IL6PIL6 chimera, as in claim 8; at [0213]-[0216].
Amit and Itskovitz-Eldor, US 10,597635, (of record, IDS), Serial No. 15403303, at col. 28, line-col. 30, line 33, teach IL6IL6 chimera and bFGF, and their use together in medium, as in claim 11; at col. 36, lines 57-col. 37, line 16, discloses that extracellular matrix, as in claim 12, can add cell attachment to cells, to provide a suitable culture substrate.
It would have been prima facie obvious before the effective filing date of the instant application, for one of ordinary skill in the art to have made and used methods for obtaining a population of mammalian livestock pluripotent stem cells, as described by Amit ‘392, with the spontaneous differentiation into adipocytes in an absence of adipogenic differentiation agent(s) thereby deriving the mammalian livestock pluripotent stem cells line. It would have been prima facie obvious before the effective filing date of the instant application, for one of ordinary skill in the art to have made and used medium comprising bFGF, WNT3A polypeptide, IL6PIL6 chimera, IL6IL6 chimera and bFGF, and addition of extracellular matrix droplets to embryos prior to culturing, as taught by Angel and Amit and Itskovitz-Eldor.
One of ordinary skill in the art would have been motivated to have combined these components, as taught by Amit’392, Saeki, Amit and Angel, and Amit and Itskovitz-Eldor, because these components are taught by the art for supporting and culturing embryo cultures.
One of ordinary skill in the art would have been motivated to have combined derived spontaneously-differentiated adipocytes in order to obtain extremely high-quality brown adipocytes that are not contaminated with or influenced by heterologous cells or exogenous cytokines the medium for culturing the embryos, as taught by Saeki.
Response to Amendment
The rejection of claim 12 over 35 USC 112(b) has been withdrawn because of applicant’s amendment to the claims, filed 12/8/25.
The prior art anticipation and obviousness rejections, presented in the non-final rejection, mailed 9/9/2025, are withdrawn because of applicant’s amendment to the claims, filed 12/8/25. However, new prior art rejections have been necessitated by applicant’s amendment to claim 1, (see, supra).
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mark L Shibuya whose telephone number is (571)272-0806. The examiner can normally be reached M-F, 9AM-4:30PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James (Doug) Schultz, can be reached at (571) 272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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MARK L. SHIBUYA
Primary Patent Examiner
Art Unit 1631
/MARK L SHIBUYA/Primary Patent Examiner, Art Unit 1631