DETAILED ACTION
Claim Status
As of the Non-Final Office Action mailed 4/7/2026, claims 1-10 were pending.
In Applicant's Response filed on 7/7/2026, claims 1-2, 4-5, and 9-10 were amended and claims 3 and 6-8 were canceled.
As such, claims 1-2, 4-5, and 9-10 are pending and have been examined herein.
Withdrawn Objections/Rejections
The objections and rejections presented herein represent the full set of objections and rejections currently pending in this application. Any objections or rejections not specifically reiterated are hereby withdrawn.
The objection of record to claim 2 for minor informalities has been withdrawn in view of Applicant’s amendment to claim 2.
The rejection of record of claims 1-10 under 35 USC § 112(b) have been withdrawn in view of Applicant’s amendment to claim 1, 4, and 9. The rejections of claims 3 and 6-8 are moot in view of their cancelation.
The rejection of record of claims 6-7 under 35 USC § 101 as being a product of nature is moot in view of the cancelation of claims 6-7.
The rejection of record of claims 6-7 under 35 USC § 102(a)(1) as being anticipated by Otero et al (Methods Mol Biology, 2012; 806:301-36) is moot in view of cancelation of these claims.
Claim Rejections - 35 USC § 103 – Modified Rejection
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
Claim(s) 1 and 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Athanasiou et al (US20090136559 A1, 7/8/2005; published 5/28/2009) in view of Tsumaki (US20160251623 A1, 10/31/2014; published 9/01/2016). Please note that this rejection has been modified based on Applicant’s amendments to claim 1.
Regarding claim 1, Athanasiou teaches chondrocyte differentiation from stem cells (abstract). It teaches a method for inducing differentiation of human embryonic stem cells into chondrocytes comprising aggregating undifferentiated human embryonic stem cells to form embryoid bodies; and culturing the embryoid bodies, or cells dissociated from the embryoid bodies, in a culture medium, wherein the culture medium comprises a growth factor that induces chondrogenic differentiation of the embryoid bodies, or of the cells (see claim 1 of Athanasiou).
Athanasiou continues to teach that the growth factor is chosen from one or more of TGF-β1, IGF-I, TGF-β3, BMP-2, and BMP-4 (see claim 9 of Athanasiou). The undifferentiated cells can be derived from induced pluripotent stem cells (see para 0036). The EBs were cultured on agarose coated plates (see para 0079).
Athanasiou does not teach that the cells are transduced with a vector containing TGF-β3.
Tsumaki teaches a novel chondrocyte induction method from pluripotent stem cells utilizing reprogramming factors such as TGF-β (see abstract and claim 1 of Tsumaki).
Tsumaki continues to teach that the reprogramming factors can be introduced into the cells via viral vectors such as retroviral, lentiviral, adenoviral, and adeno-associated vectors (see para 42 of Tsumaki).
Regarding claim 5, Tsumaki teaches that when the culturing step is performed to produce the mature chondrocytes, the medium used is a basal medium for animal cell culture, such as EMEM, DMEM, Ham’s F12, etc. (see para 80-81). The medium can contain serum or no serum and may contain one or more serum substitutes such as albumin, transferrin, KnockOut Serum Replacement (KSR) (serum substitute for FBS in ES cell culture), N2 supplement, B27 supplement, fatty acids, insulin, collagen progenitors, trace elements, 2-mercaptoethanol, and 3′-thiolglycerol, as well as one or more substances such as lipids, amino acids, L-glutamine, GlutaMAX, nonessential amino acids (NEAAs), vitamins, growth factors, low-molecular-weight compounds, antibiotics, antioxidants, pyruvic acid, buffering agents, and inorganic salt (para 81). The culture period for this step may be 20 days or more and is preferably 28 days or more (see para 82). The reference is silent to the use of recombinant growth factors in this culture step.
Tsumaki continues to teach that the resulting induced chondrocytes can have increased expression of COL2A1 and SOX9 50-fold or more (see para 85-86). The resulting chondrocytes are high-quality, and can be successfully grafted into an animal model (para 12). This shows that pluripotent stem cells can be successfully transformed into chondrocytes using vector transduction with TGF-β3.
Therefore, it would have been obvious prior to the effective filing date of the instantly claimed invention to induce chondrocytes from induced pluripotent stem cells as taught by Athanasiou, where TGF-β is introduced via vector as taught by Tsumaki, to arrive at the instantly claimed invention. Tsumaki shows that chondrocytes can successfully be produced from induced pluripotent stem cells via vector transduction of reprogramming factor TGF-β. One of ordinary skill would have been motivated to simply substitute one known element [medium containing reprogramming factor TGF-β] for another [vectors containing TGF-β] to obtain the predictable result of advantageously producing induced chondrocytes having increased expression of COL2A1 and SOX9 50-fold or more as taught by the prior art.
Response to Arguments
Applicant’s arguments have been fully considered but they are not persuasive.
On p. 8 of Remarks, Applicant argues that amending claim 1 to incorporate the subject matter of claim 3 renders the rejection moot and should be withdrawn.
While this argument has been considered, it is not persuasive. Claim 1 recites “transducing the OG cells obtained in step ii) with either or both of a minicircle vector that contains . . . BMP2 and . . . TGFβ3.” A minicircle vector containing TGFβ3 is sufficient to meet this limitation given the claim language. Although Applicant has amended claim 1 to require that the vector containing BMP2 have SEQ ID NO: 1 (previously indicated as free of prior art), and since BMP2 is not required by the claim, the vector containing SEQ ID NO: 1 is also not required by the instantly claimed method. Thus, the combination of Athanasiou and Tsumaki still render prima facie obvious the inventions of instant claims 1 and 5.
Allowable Subject Matter
Independent claim 2 recites “A method for producing chondrocytes obtained by differentiation induction from stem cells, comprising: i) culturing induced pluripotent stem cells (iPSCs) to generate embryoid bodies (EBs); ii) culturing the EBs generated in step i) in a gelatin-coated plate, to obtain outgrowth (OG) cells; iii) transducing the OG cells obtained in step ii) with a minicircle vector that contains a base sequence encoding BMP2; iv) transducing the OG cells obtained in step ii) with a minicircle vector that contains a base sequence encoding TGF33; v) performing mixed culture of the OG cells transduced in step iii) and the OG cells transduced in step iv), so that the OG cells are induced to differentiate into chondrocytes; and vi) obtaining the chondrocytes produced by differentiation induction in step v), wherein the OG cells are grown out from the EBs during culturing in step ii), and wherein the minicircle vector that contains a base sequence encoding BMP2 is a non- viral vector, the non-viral vector: (a) containing a gene expression cassette that contains a CMV promoter, a BMP2 gene consisting of the base sequence of SEQ ID NO: 1, and an SV40 polyadenylation sequence; (b) containing an att attachment sequence of bacteriophage lambda, located outside the gene expression cassette of (a); and (c) not containing a replication origin and an antibiotic resistance gene.” Dependent claims 9 and 10 recites “the method according to claim 2, wherein the minicircle vector that contains a base sequence encoding TGFβ3 is a non-viral vector, the nonviral vector, (a1) containing a gene expression cassette that contains a CMV promoter, a TGFβ3 gene consisting of the base sequence of SEQ ID NO:2, and an SV40 polyadenylation sequence; (b1) containing an att attachment sequence of bacteriophage lambda, located outside the gene expression cassette of (a1); and (c1) not containing a replication origin and an antibiotic resistance gene” and “the method according to claim 2, wherein the step of inducing differentiation of the OG cells into chondrocytes is performed by culturing the OG cells in a medium containing no recombinant growth factor for 3 to 30 days”, respectively.
The closest prior art, Athanasiou, teaches chondrocyte differentiation from stem cells (abstract). It teaches a method for inducing differentiation of human embryonic stem cells into chondrocytes comprising aggregating undifferentiated human embryonic stem cells to form embryoid bodies; and culturing the embryoid bodies, or cells dissociated from the embryoid bodies, in a culture medium, wherein the culture medium comprises a growth factor that induces chondrogenic differentiation of the embryoid bodies, or of the cells. Tsumaki (of record) teaches a novel chondrocyte induction method from pluripotent stem cells utilizing reprogramming factors such as TGF-β (see abstract and claim 1 of Tsumaki). Tsumaki continues to teach that the reprogramming factors can be introduced into the cells via viral vectors such as retroviral, lentiviral, adenoviral, and adeno-associated vectors (see para 42 of Tsumaki). However, claim 2 (and its dependents) requires SEQ ID NO: 1, which is not taught or suggested by prior art.
Claim 4 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. SEQ ID NO. 2, which is required by instant claim 4, is free of the prior art.
Conclusion
Claims 1 and 5 are not allowed.
Claim 4 is objected to for being dependent on a rejected claim.
Claims 2 and 9-10 contain allowable subject matter.
THIS ACTION IS MADE FINAL. 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.
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/G.R./Examiner, Art Unit 1632
/MARCIA S NOBLE/Primary Examiner, Art Unit 1632
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