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 .
Claims 1-9 and 19-22 are pending in this application.
Election/Restrictions
Applicant’s election without traverse of Claims 1-10, cancellation of Claims 10-18 and addition of New Claims 19-22 in the reply filed on 03/12/2026 is acknowledged.
Claims 1-9 and 19-22 were examined on their merits.
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.
Claim 8 is 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. Claim 8 recites, “the fragmented matrix component is disposed in a gap among the cells in the three-dimensional construct”. It is unclear how the fragmented matrix component is only disposed in a single gap between multiple cells in a 3D construct, such that the metes and bounds of the claim can be determined. That is, is the fragmented matrix component disposed among all of the gaps between all of the cells in the construct or just in a single gap? For purposes, of examination the Examiner has interpreted the limitation as being met by a fragmented matrix component disposed being located in a gap between at least two cells of a 3D construct.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1 and 4 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by Zeng et al. (2018), cited in the IDS.
Zeng et al. teaches a method comprising incubating isolated (therefore not comprising any mature adipocytes) human adipose derived stem cells (hADSC) in the presence of oleic acid to induce adipogenesis of the hADSC (Pgs. 2-3, Paragraph “Culture and Differentiation” and Pg. 3, Column 2, 2nd paragraph).
Claim(s) 1, 4 and 6 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by Turner et al. (2017), cited in the IDS.
Turner et al. teaches a method comprising incubating isolated (therefore not comprising any mature adipocytes) human adipose stem cells (hASC) in the presence of oleic acid for 10 days (240 hours) to induce adipogenesis of the hASC (Pg. 313, Column 1, and paragraph and Pgs. 313-314, Paragraphs 2.3-2.5).
Claim(s) 1, 4, 5, 6, 7, 20, 21 and 22 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by Kang et al. (08/24/2021), cited in the IDS.
Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55.
When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
Kang et al. teaches incubating isolated (therefore not comprising any mature adipocytes) bovine adipose derived stem cells (bADSCs) in the presence of fibrinogen, thrombin, ALK5i II TGF-β inhibitor, erucic acid, elaidic acid, oleic acid, palmitoleic acid, myristoleic acid, phytanic acid and pristanic acid for 120-312 hours (Pg. 9, Column 1, Paragraph “Isolation and purification…” and Column 2, Paragraph “3D gel-embedded culture” and Pg. 4, Fig. 2d, #1).
Claim(s) 1, 4, 5 and 6 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by Mehta et al. (2019), as evidenced by Bourin et al. (2014).
Mehta et al. teaches incubating isolated (therefore not comprising any mature adipocytes which are in the aqueous supernatant, see Pg. 117, Fig. 1) bovine adipose stromal vascular cells/adipogenic precursors (e.g. containing adipose derived stromal/stem cells, as evidenced by Bourin et al., Pg. 3, 3rd paragraph) for 1-2 weeks (or 168-336 hours) (Pg. 116-117, Methods, 3.1 and Fig. 1) in the presence of: erucic acid, elaidic acid, oleic acid, palmitoleic acid, myristoleic acid, phytanic acid and pristanic acid for 120-312 to induce adipogenesis (Pg. 112, Table and Pg. 119, Paragraph 3.2), and reading on Claims 1, 4, 5 and 6.
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.
Claim(s) 1, 4, 5, 6 and 19 are rejected under 35 U.S.C. § 103 as being unpatentable over Mehta et al. (2019), as evidenced by Bourin et al. (2014), as applied to Claims 1, 4, 5 and 6 above, and further in view of Zeng et al. (2018), cited in the IDS.
The teachings of Mehta et al. were discussed above.
Mehta et al. did not teach a method wherein the content of each of the fatty acids in the culture medium is 80-120 µM, as required by Claim 19.
Zeng et al. teaches a method comprising incubating isolated human adipose derived stem cells (hADSC) in the presence of; 50, 80 or 100 µM oleic acid to induce adipogenesis of the hADSC (Pgs. 2-3, Paragraph “Culture and Differentiation” and Pg. 3, Column 2, 2nd paragraph).
While the references listed above do not specifically teach the limitations of the concentration of all of the fatty acids in the composition being 80-120 µM, one of ordinary skill in the art would recognize that the concentration of each of the fatty acids in a adipogenic composition is a result-effective optimizable variable. Zeng et al. teaches that the fatty acid oleic acid can induce adipogenesis in adipose derived stem cells at concentrations of 50, 80 or 100 µM. This is motivation for someone of ordinary skill in the art to practice or test all of the fatty acid concentration parameter values widely to find those that are functional or optimal for induction of adipogenesis, which would be inclusive or cover the values as instantly claimed. Absent any teaching of criticality by the Applicant concerning the fatty acid concentration in the composition, it would be prima facie obvious that one of ordinary skill in the art would recognize these limitations are an optimizable variable which can be met as a matter of routine optimization (see MPEP § 2144.05 (II)(B).
Claim(s) 1, 2, 3, 4, 5, 6 and 20 are rejected under 35 U.S.C. § 103 as being unpatentable over Mehta et al. (2019), as evidenced by Bourin et al. (2014), as applied to Claims 1, 4, 5 and 6 above, and further in view of Lemenager et al. (2020), cited in the IDS.
The teachings of Mehta et al. were discussed above.
Mehta et al. did not teach a method wherein the cells are incubated in the presence of a TGFβ type I receptor inhibitor at a concentration of 1-10 µM, as required by Claims 2 and 3;
or wherein the TGFβ type I receptor inhibitor is an ALK5 inhibitor, as required by Claim 20.
Lemenager et al. teaches culturing human adipose stem cells (hASC) in the presence of 1 µM of the TGFβ type I receptor inhibitors, SB431542 or SB505124 ALK5 (Pgs. 783-784, Paragraph 2.1) wherein TGFβ type I receptor inhibition increased the cells adipogenic potential (Pg. 782, Abstract).
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Mehta et al. of incubating cells comprising adipose stem cells with free fatty acids to induce adipogenesis to include 1 µM of the TGFβ type I receptor inhibitor SB505124 ALK5 because this would increase the adipogenic potential of the stem cells in the composition. Those of ordinary skill would have been motivated to make this modification in order to produce more adipocytes from the adipose stem cells in the composition. There would have been a reasonable expectation of success in making this modification because both methods are reasonably drawn to the same field of endeavor, that is, the induction of adipogenesis of adipose-derived stem cells.
Claim(s) 1, 2, 3, 4, 5, 6, 7, 8, 9 and 20 are rejected under 35 U.S.C. § 103 as being unpatentable over Mehta et al. (2019), as evidenced by Bourin et al. (2014), in view of Lemenager et al. (2020), cited in the IDS, as applied to Claims 1, 2, 3, 4, 5, 6 and 20 above, and further in view of Louis et al. (2019), cited in the IDS.
The teachings of Mehta et al. and Lemenager et al. were discussed above.
Neither reference taught a method wherein the cells are incubated with a TGFβ type I receptor inhibitor and fragmented collagen disposed between the cells in a 3D construct, as required by Claims 7-9.
Louis et al. teaches incubating adipose derived stem cells with homogenized (defibered) fragmented collagen (microfibers) (Pgs. 195-196, Paragraph 2.1) disposed between the cells in a 3D construct (Pg. 196, Fig. 1B) wherein the construct increased adipogenic gene expression and produced larger fat vesicles as well as increased markers of functionality (Pg. 194, Abstract).
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Mehta et al. and Lemenager et al. of incubating cells comprising adipose stem cells with free fatty acids and TGFβ type I receptor inhibitor SB505124 ALK5 to induce optimal adipogenesis to include fragmented collagen microfibers disposed between the cells in a 3D construct as taught by Louis et al. because this would further increase the adipogenic potential of the stem cells in the composition. Those of ordinary skill would have been motivated to make this modification in order to produce more adipocytes from the adipose stem cells in the composition. There would have been a reasonable expectation of success in making this modification because all three references are reasonably drawn to the same field of endeavor, that is, the induction of adipogenesis of adipose-derived stem cells.
Claim(s) 1, 2, 3, 4, 5, 6, 7, 8, 9, 20 and 21 are rejected under 35 U.S.C. § 103 as being unpatentable over Mehta et al. (2019), as evidenced by Bourin et al. (2014), in view of Lemenager et al. (2020), cited in the IDS, as applied to Claims 1, 2, 3, 4, 5, 6 and 20 above, and further in view of Louis et al. (2019), cited in the IDS and Yoo et al. (2012).
The teachings of Mehta et al. and Lemenager et al. were discussed above.
Neither reference taught a method wherein the adipose stem cells are incubated in a fatty acid culture medium comprising a defibered collagen component, fibrinogen and thrombin, as required by Claim 21.
Louis et al. teaches incubating adipose derived stem cells with homogenized (defibered) fragmented collagen (microfibers) (Pgs. 195-196, Paragraph 2.1) disposed between the cells in a 3D construct (Pg. 196, Fig. 1B) wherein the construct increased adipogenic gene expression and produced larger fat vesicles as well as increased markers of functionality (Pg. 194, Abstract).
Yoo et al. teaches the transplantation of adipose stem cells (ASC) to an ischemic bowel wall in a mixture of thrombin and fibrinogen for stable fixation to the bowel wall (Pg. 134, Columns 1-2, “Local Implantation” and Fig. 1).
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Mehta et al. and Lemenager et al. of incubating cells comprising adipose stem cells with free fatty acids and TGFβ type I receptor inhibitor SB505124 ALK5 to induce optimal adipogenesis to include fragmented collagen microfibers disposed between the cells in a 3D construct as taught by Louis et al. and thrombin and fibrinogen as taught by Yoo et al. because this would further increase the adipogenic potential of the stem cells in the composition as well as provide a stable matrix for transplantation in vivo. Those of ordinary skill would have been motivated to make this modification in order to produce more adipocytes from the adipose stem cells in the composition and stably transplant those cells to a subject. There would have been a reasonable expectation of success in making this modification because all three references are reasonably drawn to the same field of endeavor, that is, the induction of adipogenesis of adipose-derived stem cells or the use thereof.
Claim(s) 1, 2, 3, 4, 5, 6, 7, 8, 9, 20, 21 and 22 are rejected under 35 U.S.C. § 103 as being unpatentable over Mehta et al. (2019), as evidenced by Bourin et al. (2014), in view of Lemenager et al. (2020), cited in the IDS, Louis et al. (2019), cited in the IDS and Yoo et al. (2012), as applied to Claims 1, 2, 3, 4, 5, 6, 20 and 21 above, and further in view of Ichida et al. (US 2012/0021519 A1).
The teachings of Mehta et al., Lemenager et al., Louis et al. and Yoo et al. were discussed above.
None of the above references taught a method wherein the culture medium comprises the TGFβ type I receptor inhibitor E-616452, as required by Claim 22.
Ichida et al. teaches the TGFβ type I receptor inhibitors RepSox, E-616452 and SB431542 (as taught by Lemenager et al.) (Pg. 87, Paragraph [
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Mehta et al., Lemenager et al. and Louis et al. of incubating cells comprising adipose stem cells with free fatty acids and TGFβ type I receptor inhibitor SB431542 or SB505124 ALK5, thrombin, fibrinogen and fragmented collagen microfibers disposed between the cells in a 3D construct to substitute the E-616452 TGFβ type I receptor inhibitor of Ichida et al. for the SB431542 TGFβ type I receptor inhibitor of Lemenager et al. because it is prima facie obvious to substitute art-recognized equivalents for the same purpose. See the MPEP at 2144.06, II. Those of ordinary skill would have been motivated to make this modification in order to reduce TGFβ inhibition of adipogenesis to produce more adipocytes from the adipose stem cells in the composition. There would have been a reasonable expectation of success in making this modification because the art recognizes SB431542 and E-616452 as equivalent inhibitors of TGFβ type I receptor.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to PAUL C MARTIN whose telephone number is (571)272-3348. The Examiner can normally be reached Monday-Friday 12pm-8pm EST.
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If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Sharmila G 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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/PAUL C MARTIN/Examiner, Art Unit 1653 04/03/2026
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