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 .
Detailed Action
This action is in response to the papers filed August 6, 2026.
Claim Amendments
Applicant’s amendment to the claims filed 08/06/2026 is acknowledged.
Claims 5, 7, 12-13, 16-17 have been canceled.
Claim 1, 9, 14-15, 18-19 are amended.
Claims 21-26 are newly added.
Claims 1-4, 6, 8-11, 14-15, 18-26 are pending and under examination.
Priority
The instant application 18/704,322 was filed on 04/24/2024. This application is a national stage of international application PCT/JP2022/040212 filed 10/27/2022, claiming priority based on Japanese patent application JP2021-177295 filed 10/29/2021.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. While a certified copy of the foreign patent application is provided with the instant application, a certified English translation of said foreign patent application has not been provided.
Withdrawal of Prior Rejections/Objections
Rejections and/or objections not reiterated from the previous Office action mailed 05/26/2026 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
Claim Objections
Claim 2 is objected to because of the following informalities:
The phrase “the cells comprising at least adipose-derived stem cells from human” in claim 2 should be “the cells comprising at least adipose-derived stem cells from human and mature adipocytes” instead, as initially recited in claim 1.
Appropriate action is required.
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 6, 8, 14-15, 19-20 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.
Claim 6 is indefinite because the claim recites dependency on a canceled claim. Further, the limitation “the fragmented extracellular matrix component” lacks antecedent basis.
Claim 8 is indefinite because the claim recites dependency on a canceled claim. Further, the limitation “the fragmented extracellular matrix component” lacks antecedent basis.
Claim 14 is indefinite because the claim recites dependency on a canceled claim.
Claim 15 is indefinite because the claim recites dependency on a canceled claim.
Claim 19 is indefinite because the limitation “the fragmented extracellular matrix component” lacks antecedent basis.
Claim 20 is indefinite because the claim recites dependency on a canceled claim.
For these reasons, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
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.
Claims 1-4, 6, 8-11, 14-15, 18-26 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2020/203369 A1 to Kitano et al.; in view of CN110713984A to Hongxin et al. (published: 2020-Jan-21).
WO 2020/203369 A1 to Kitano et al.; was published in a non-English language. This rejection relies on a machine translation from PE2E, which is provided with this Office action.
CN110713984A to Hongxin et al. was published in a non-English language. This rejection relies on a machine translation from Espacenet.com, which has been provided in a previous Office action.
Regarding the teachings of the prior art, Kitano discloses a method producing a three-dimensional tissue construct comprising a fragmented extracellular matrix component and cells comprising at least fat cells (adipocytes) and vascular endothelial cells, wherein the tissue construct possesses an intracellular vascular network. See, e.g., page 2 of the translation.
The cells are derived from a mammal, such as a human, and the cells may include a stem cell, such as a human adipose stem cell (ADSC). The cells includes at least adipocytes and vascular endothelial cells. The term “adipocyte” includes all adipocytes except adipose stem cells, but the adipocytes are preferably mature adipocytes. The term “vascular endothelial cell” includes human umbilical vein-derived vascular endothelial cells (HUVECs). See, e.g., page 3 of the translation.
The fragmented extracellular matrix component is a fragmented collagen component, including a defibrated collagen component. The average length of the fragmented extracellular matrix component is 100 nm or more and 200 μm or less. See, e.g., pages 4-5 and 15 of the translation.
The method comprises a step of contacting the fragmented extracellular matrix component with the cells comprising at least mature adipocytes, adipose stem cells, and vascular endothelial cells in an aqueous medium. See, pages 8-9 of the translation. The method further comprises a culturing step in an aqueous medium. See, e.g., page 11 of the translation. The order in which the cells and fragmented extracellular matrix component are added is not particular limited, and they may be mixed by stirring or the like. See, page 9 of the translation.
The tissue construct further contains fibrin by contacting fibrinogen with thrombin. In particular, fibrinogen and thrombin are added to the tissue construct during the contact step, or after the contact step and before the culture step. See, e.g., pages 8 and 10 of the translation.
The difference between the instantly claimed invention and that of Kitano is the claims further recite incubation in the presence of a TGFβ type I receptor inhibitor.
Hongxin is relevant prior art for disclosing a method comprising incubating human adipose-derived mesenchymal stem cells in the presence of TGFβR1 (ALK5) inhibitor SB431542 to induce generation of vascular endothelial cells. The induced vascular endothelial cells form a tubestructure (vascular network) in vitro, and reconstruction of blood vessels is promoted after in vivo transplantation. See, pages 1, 3-5, 7-8 of the translation.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the invention of Kitano by further including a TGFβ type I receptor inhibitor, in view of Hongxin; with a reasonable expectation of success because Kitano is directed toward manufacture of a three-dimensional tissue construct possessing a vascular network, and the addition of a TGFβ type I receptor inhibitor, as in Hongxin, would promote induction of vascular endothelial cells and the formation of a vascular network.
Hongxin further discloses the inhibitor is added to the culture medium at a concentration of 10 μM. See, page 7 of the translation. Incubation with the inhibitor occurs for 4 days, which is equivalent to 96 hours. See, page 3 of the translation.
Kitano further discloses that the aqueous medium is EGM®-2 medium (see, pg. 16-17 of the translation), which is a media composition comprising vascular endothelial grow1h factor (VEGF). In addition, Kitano discloses the induction media contains 50 ng/mL of VEGF. See, page 4 of the translation.
Hongxin does not teach the inhibitor is 2-[3-(6-methyl-2-pyridinyl)-1H-pyrazol-4-yl]-1,5-naphthyridine (RepSox), as instantly claimed. However, RepSox was a well understood TGFβR1 (ALK5) inhibitor prior to the effective filing date of the instantly claimed invention. Accordingly, one of ordinary skill in the art, when considering the Hongxin disclosure, would have recognized that SB431542 and RepSox are functional alternatives for inhibition of TGFβR1 (ALK5). Therefore, it would have been prima facie obvious to one of ordinary skill in the art to substitute SB431542 with RepSox with a reasonable expectation of success because both compounds are TGFβR1 (ALK5) inhibitors that would have been expected to promote induction of vascular endothelial cells, and the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention
For these reasons, claims 1-4, 6, 8-11, 14-15, 18-26 would have been prima facie obvious over the prior art.
The Examiner acknowledges that Applicant has asserted unexpected results in the reply filed 08/06/2026 when the claims were previously rejection under 35 U.S.C. 102 for anticipated by the Hongxin disclosure. See, pages 7-8 of the reply. It is the Examiner’s position that the amendment to the claims has significantly modified in scope of the instantly claimed method, and the closest prior art of record is now Kitano, not Hongxin. Accordingly, any assertion of unexpected results must take into consideration the Kitano reference. Moreover, based on the description provided in the working examples of the specification, the asserted unexpected results appear to rely on features not claimed. In particular, the working examples rely on use of (i) an ALK5 inhibitor (RepSox) and (ii) a culture medium containing VEGF (EGM®-2). In contrast, the claims recite use of an inhibitor of TGFβ type I receptors, which is a genus broadly including receptors other than ALK5, e.g., ALK2, ALK4 and ALK7. Regarding the significance of VEGF, see, e.g., paragraph [0131] of the specification: “From these results, it was shown that in a case where VEGF is added to a culture medium in addition to the ALK-5 inhibitor, the differentiation of adipose-derived stem cells from human into vascular endothelial cells and angiogenesis are further promoted.”
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 JAMES J GRABER whose telephone number is (571)270-3988. The examiner can normally be reached Monday-Thursday: 9:00 am - 4:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James D 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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/JAMES JOSEPH GRABER/Examiner, Art Unit 1631
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