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 the Claims
Applicant’s submission filed 30 December 2025 has been entered. Claims 9-12, 15-16, 20-21, 23 and 27 are pending. Claims 9, 16, 20-21, 23, and 27 have been amended. Therefore, prosecution on the merits continues for claims 9-12, 15-16, 20-21, 23 and 27. All arguments have been fully considered with the status of each prior ground of rejection set forth below.
Status of Prior Rejections/Response to Arguments
RE: Rejection of claims 9-12, 15-16, 20-21, 23, and 27 under 35 USC 102(a)(1) and 35 USC 102(a)(2) over O’Heeron
Applicant has amended independent claims 9, 20, and 23 to require the member protein of step a) and the member protein encoded by the gene of step b) to be the same member protein selected from the group consisting of TGF-β1, TGF-β2, TGF-β3, BMP-2, BMP-3, BMP-4, BMP-6, BMP-7, and BMP-9. As Applicant has narrowed the scope of a previously recited limitation – since the limitations previously presented within claims 16, 21, and 27 did not necessarily require the member proteins of step a) and step b) to be the same – Applicant’s amendments obviate the rejection of record.
Therefore, the rejection is withdrawn.
However, Applicant’s arguments are addressed in so far as they are applicable to the new 35 USC 103 rejection of record, which utilizes O’Heeron:
Applicant has traversed the rejection, asserting in Page 11 of the Remarks filed 30 December 2025 that O’Heeron does not disclose the synergistic effect that the administration of the same exogenous and gene-encoded growth factor boasts from the dual-administration, and instead utilizes the growth factors as generic additives. In response, the Examiner respectfully submits that Applicant has not provided sufficient evidence that the dual-administration of exogenous and gene-encoded growth factors results in a synergistic effect. More specifically, Applicant has provided working examples that showcase either (i) the administration of fibroblasts comprising gene-encoded TGF-β1 compared to control fibroblasts not comprising a gene-encoded TGF-β1, or (ii) the administration of exogenous recombinant TGF-β1 and normal chondrocytes compared to control normal chondrocytes. See Paragraphs [00146]-[00173] of the instant Specification filed 29 September 2021. Therefore, Applicant has failed to demonstrate the dual-administration of an exogenous growth factor and HEK cells or epithelial cells comprising the same gene-encoded growth factor, nor that the dual-administration boasts a synergistic effect. See MPEP § 716.02(a).
Furthermore, the Examiner notes that the evidence relied upon is not commensurate in scope with the claims as written, as they are limited to TGF-β1 and do not encompass the broader scope of the recited member proteins. See MPEP § 2145.
Therefore, the administration of the member protein in step a) and population of cells in step b) containing the same encoded member protein will read on the methods of the instant claims.
New Grounds of Rejection
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 9-12, 15-16, 20-21, 23, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over O’Heeron (US 2016/0220699 A1) in view of Shi et al (J Orthop Res, 2013).
O’Heeron is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2). Shi et al is considered prior art under 35 USC 102(a)(1).
Regarding claims 9, 16, 20-21, 23, and 27: O’Heeron discloses the use of gene therapy for the attraction, generation and/or regeneration of chondrocytes or other cartilage-type cells and/or the generation and/or repair of cartilage tissue – including articular cartilage (Abstract; Paragraphs [0005]-[0006], [0009]). O’Heeron further discloses the treatment of osteoarthritis within a subject (Paragraph [0160]).
As such, O’Heeron discloses the transformation of host mammalian cells with a vector encoding a transforming growth factor beta (TGF-β) protein to form a gene therapy composition, wherein the host cells are either epithelial cells or 293 cells (293 cells being embryonic kidney cells) (Paragraphs [0016], [0043]-[0045], [0057], [0062]-[0064], [0067], [0147], [0149], [0152]). O’Heeron further discloses that the TGF-β can be TGF-β1 (Paragraph [0050]).
With that, O’Heeron further discloses that the gene therapy composition is subsequently administered to at least one joint of the subject in need thereof, such that cartilage or connective tissue is regenerated in the respective joint (Paragraphs [0161]-[0162]). It is of note that the gene therapy composition can comprise a plurality of cells (Paragraph [0161]).
O’Heeron further discloses that, in the case wherein there is cell manipulation outside the body followed by delivery of the cells to the subject in need thereof, one or more growth factors are provided to the subject in combination with the gene therapy composition. O’Heeron discloses that such growth factors are TGF-β or bone morphogenetic proteins (Paragraph [0037]).
O’Heeron does not disclose that the TGF-β growth factor is the same as the TGF-β1 protein encoded within the vector, as required in instant claims 9, 16, and 23.
Shi et al, however, disclose either the administration of recombinant TGF-β1 or gene-edited articular chondrocytes comprising encoded TGF-β1 for the regeneration of articular cartilage (Abstract; Pages 2-3). As such, Shi et al disclose that the administration of recombinant TGF-β1 allowed for greater chondrocyte proliferation, GAG production, and aggrecan gene expression when compared to the gene-encoded TGF-β1 (Pages 4-7; Figures 1-5; Table 2).
Therefore, it would have been prima facie obvious to have modified the method of O’Heeron such that recombinant TGF-β1 is delivered with the cells, as detailed in Shi et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to administer TGF-β1 as the growth factor, as it would bolster the gene-encoded TGF-β1 response in regards to chondrocyte proliferation, GAG production, and aggrecan gene expression for the regeneration of articular cartilage, and would have had a reasonable expectation of success given that O’Heeron discloses the administration of TGF-β in conjunction with the cells. See MPEP § 2143(I)(G).
Consequently, O’Heeron as modified by Shi et al render obvious the regeneration of articular cartilage within an arthritic joint space of a subject, wherein host mammalian cells are first transfected with a vector encoding TGF-β1 to form a gene therapy composition. This gene therapy composition is then administered to the subject, in combination with recombinant TGF-β1 (claims 16, 21, and 27) and a pharmaceutically acceptable carrier, via intra-articular injection. As the host mammalian cells are epithelial cells or human embryonic kidney cells, and articular cartilage is a type of hyaline cartilage, this therefore reads on the method of instant claims 9 and 20.
In addition, due to the fact O’Heeron describes the cartilage tissue as a kind of connective tissue (Paragraph [0013]), this also reads on the method of instant claim 23. It is emphasized that an arthritic joint reads on an injured connective tissue.
Regarding claims 10-12: Following the discussion of claim 9, O’Heeron further discloses that the vector is either a retroviral vector (claims 10-11) or a plasmid (claim 12) (Paragraphs [0055]-[0056], [0069], [0098], [0103], [0110], [0151]). This therefore reads on the method of the instant claims.
Regarding claim 15: Following the discussion of claim 9, O’Heeron further discloses that the cells are autologous or allogenic cells (Paragraphs [0031], [0042]). This therefore reads on the method of the instant claim.
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 ALYSSA G WESTON whose telephone number is (571)272-0337. The examiner can normally be reached Monday-Thursday 8AM - 4PM (CT); Friday 8AM - 11AM (CT).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALYSSA G WESTON/Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633