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 .
Election/Restrictions
Applicant’s election without traverse of Group 1, claims 1-6, 8-11, 17-20, 23-25, and 28 in the reply filed on 02 February 2026 is acknowledged.
Claims 32-33 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 02 February 2026.
Priority
This application is a 371 of PCT/US22/21156, filed 21 March 2022 which claims benefit of 63/163,528, filed 19 March 2021.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/163,528, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
The disclosure of Application No. 63/163,528 fails to provide support for the full disclosure of claims 6, 8, 9, 24, and 25, therefore, the effective filing date for these claims is 21 March 2022.
Specifically, claim 6 does not find support for an AAV viral vector. Claim 8 does not find support for a PMEPA1 promoter, a FGF1 promoter, a SNORA70 promoter, a IGSF9B promoter, a NR4A2 promoter, a NR4A1 promoter, a INHBA promoter, a CSRNP2 promoter, a PHLDA1 promoter, a GAN promoter, a SLC25A25 promoter, a SLC35E4 promoter, a CAND2 promoter, a SNCAIP promoter, a WNT9A promoter, a EGR1 promoter, a DUSP2 promoter, a SPRY4 promoter, or combinations comprising these promoters. Claim 9 does not find support for an anti-catabolic polypeptide, a pro-anabolic polypeptide, a pro-regenerative polypeptide, an anti- microbial polypeptide, an anti-pain polypeptide, a morphogen, a growth factor, an anti-cancer nucleic acid or an anti-cancer polypeptide. Claim 24 does not find support for a NR4A2 promoter, a NR4A1 promoter, a WNT9A promoter, a SPRY4 promoter, and combinations thereof. Claim 25 does not find support for sTNFR1/2, IL-10 IL-4, a growth factor from the TGF superfamily, IGF, CTGF, FGF, PDGF, a kappa opioid ligand pro-peptide (e.g., prodynorphin), a mu/delta opioid ligand pro-peptide (e.g., proenkephalin), a delta/mu opioid ligand pro-peptide (proopiomelanocortin), an endocannabinoid ligand synthesis drivers TNF, IL-7, IL-15, IL-12, IL-2, IFN, NOS, PTGIS, Decorin, TGF - receptor, MMP, ALDH2, NR3C1 and any combination thereof.
Claims 1-5, 10-11, 17-20, 23, and 28 find support in the disclosure of Application No. 63/163,528, therefore, the effective filing date for these claims is 19 March 2021.
Claim Status
Claims 7, 12-16, 21-22, 26-27, and 29-31 were previously canceled, claims 3-4, 8-11, 17, 25, 28, and 32-33 are currently amended, claims 32-33 have been withdrawn as being directed to a non-elected invention, and claims 1-6, 8-11, 17-20, 23-25, and 28 have been considered on their merits.
Claim Objections
Claim 2 is objected to because of the following informalities: In the second line of the claim, the term “nucleic acid sequence” is stated twice in a row.
Claims 8, 23, 24, and 25 are objected to because of the following informalities: these claims use abbreviations which have not been spelled out upon first use. Although claims are allowed abbreviations, if an abbreviation is not spelled out upon first use in a claim, MPEP § 2429 states that Applicant only use abbreviations that are specifically defined in "WIPO Standard ST.25 (1998)" or that are well known and would be clear to someone who had not read the invention description.
Claim 8 is objected to because of the following informalities: In the first line of the claim there should be an “of” in front of “claim 2”.
Claim 9 is objected to because of the following informalities: In the second and third line of the claim, “an anti microbial polypeptide” should read “an anti-microbial polypeptide” and “an anti cancer nucleic acid” should read “an anti-cancer nucleic acid. Additionally, in the last line of the claim, “anti-cancer polypeptides” should be “anti-cancer polypeptide”.
Claim 25 is objected to because of the following informalities: In the third line of the claim, between IL-10 and IL-4, there should be a comma.
Appropriate correction 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 24 and 25 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 24 recites the limitation "the promoter" in the first line of the claim. There is insufficient antecedent basis for this limitation in the claim. Claim 24 ultimately depends from claim 11, which comprises the nucleic acid sequence of claim 1. Claim 1 requires a transcriptional regulatory nucleic acid sequence, not a promoter.
Claim 25 recites the phrases “a kappa opioid ligand pro-peptide (e.g., prodynorphin), a mu/delta opioid ligand pro-peptide (e.g., proenkephalin), a delta/mu opioid ligand pro-peptide (proopiomelanocortin)…” which renders the claim indefinite because it is unclear whether the limitation in parenthesis are part of the claimed invention. MPEP § 2173.05(d) states, description of examples or preferences is properly set forth in the specification rather than the claims. If stated in the claims, examples and preferences may lead to confusion over the intended scope of a claim. Therefore, it is unclear whether the information in parentheses is exemplary or a limitation of the claim.
Claim 25 appears to recite several groups and subgroups of the therapeutic biologic nucleic acid molecule, it is unclear if the “any combination thereof” at the end of the claim is referring to an endocannabinoid ligand synthesis driver or any of the therapeutic biologic nucleic acid molecules. It is also unclear if TNF is meant to be a part of an endocannabinoid ligand synthesis driver or a separate limitation. The language of a claim must make it clear what subject matter the claim encompasses to adequately delineate its "metes and bounds". See, e.g., the following decisions: In re Hammack, 427 F 2d. 1378, 1382, 166 USPQ 204, 208 (CCPA 1970); In re Venezia 530 F 2d. 956, 958, 189 USPQ 149, 151 (CCPA 1976); In re Goffe, 526 F 2d. 1393, 1397, 188 USPQ 131, 135 (CCPA 1975); In re Watson, 517 F 2d. 465, 477, 186 USPQ 11, 20 (CCPA 1975); In re Knowlton 481 F 2d. 1357, 1366, 178 USPQ 486, 492 (CCPA 1973).
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-6, 8-11, 17-20, 23-25, and 28 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nims et al. (Sci. Adv. 2021; 7, published 27 January 2021, IDS ref.).
Although the Nims reference cited above lists the inventors as three of the thirteen authors of the reference, it is still applicable as prior art under 35 U.S.C. 102(a)(1).
Applicant may rely on the exception under 35 U.S.C. 102(b)(1)(A) to overcome this rejection under 35 U.S.C. 102(a)(1) by a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application, and is therefore not prior art under 35 U.S.C. 102(a)(1). Alternatively, applicant may rely on the exception under 35 U.S.C. 102(b)(1)(B) by providing evidence of a prior public disclosure via an affidavit or declaration under 37 CFR 1.130(b).
Regarding claims 1 and 2, Nims teaches a mechanically responsive bioartificial tissue construct for therapeutic drug delivery by using the signaling pathways downstream of the mechano/osmosensitive ion channel TRPV4 to drive synthetic mechanogenetic gene circuits (p. 1, 2nd column). Nims teaches synthetic gene circuits to respond to mechanical TRPV4 activation for driving transgene production of an anti-inflammatory molecule, interleukin-I receptor antagonist (IL-1Ra) (therapeutic biologic, claim 1) (p. 2, 1st column). Nims teaches the TRPV4-responsive gene circuit comprises the PTGS2 promoter (transcriptional regulatory nucleic acid sequence, claims 1 and 2) (Fig. 1 and p. 4, Synthetic mechanogenetic circuits respond to TRPV4 activation to drive transgene expression).
Regarding claim 3, Nims teaches a TATA box derived from the minimal CMV promoter was cloned between the synthetic promoter and downstream target genes (p. 11, NFKBr circuit design).
Regarding claims 4-6 and 8, Nims teaches a synthetic human PTGS2 promoter (claim 8) was cloned into the NFKBr-IL1Ra lentiviral transfer vectors (claims 4-6) in place of the NF-KB-inducible promoter (p. 11, PTGS2r circuit design). The lentiviral vector reads as a viral vector.
Regarding claim 9, the IL-1Ra transgene of Nims (p. 2, 1st column) reads as an anti-inflammatory polypeptide.
Regarding claim 10, the lentiviral vector comprising the PTGS2 promoter and IL-1Ra transgene of Nims read on the limitations of the claim.
Regarding claim 11, Nims teaches transduction of chondrocytes with the PTGS2r-IL1Ra lentiviral vectors (p. 11, Lentivirus production and chondrocyte transduction).
Regarding claims 17-20 and 23, Nims teaches chondrocytes comprise TRPV4 (claims 18-19) and PIEZ01 and PIEZ02 (claim 23), which are mechanically sensitive ion channels (claim 17) (p. 2, 2nd column).
Regarding claim 24, Nims teaches synthetic NF-KB-inducible promoter was designed to incorporate multiple NF-KB response elements, wherein, a synthetic promoter was developed containing five consensus sequences approximating the NF-KB canonical recognition motif based on genes up-regulated through inflammatory challenge to include Adamts5 (p. 11, NFKBr circuit design). This reads as the promoter of the mechanically-responsive gene is an ADAMTS1 promoter.
Regarding claims 25 and 28, Nims teaches transduction of chondrocytes with the PTGS2r-Il1Ra lentiviral vectors (p. 11, Lentivirus production and chondrocyte transduction). This reads as the therapeutic biologic nucleic acid molecule encodes IL-1Ra (claim 25). The vector described by Nims reads as the therapeutic biologic (IL-1Ra) expression period is modulated through the transcriptional regulatory nucleic acid molecule of a mechanically responsive gene (PTGS2 promoter). Therefore, the chondrocytes of Nims read on the limitations of claim 28.
Thus, the reference anticipates the subject matter of claims 1-6, 8-11, 17-20, 23-25, and 28.
Claims 1-6, 8-9, 11, 17-20, 23-25, and 28 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pferdehirt et al. (Tissue Engineering: Part A, Volume 25, Numbers 9 and 10, 2019, IDS ref.) as evidenced by Nims et al. (Sci. Adv. 2021; 7, published 27 January 2021, IDS ref.).
Regarding claims 1 and 2, Pferdehirt teaches an artificial gene circuit for controlled, cell-based delivery of biologic drugs (therapeutic biologic), based on a nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-responsive synthetic promoter (claim 2) (Abstract). The NFkB-responsive synthetic promoter of Pferdehirt reads as a transcriptional regulatory nucleic acid sequence of a mechanically-responsive gene.
Regarding claim 3, Pferdehirt teaches a TATA box derived from the minimal CMV promoter was cloned between the synthetic promoter and downstream target genes; and an NF-κB negative regulatory element was cloned upstream of the promoter (p. 810, Vector design).
Regarding claims 4-6, 9, and 11, Pferdehirt teaches lentivirus-based gene therapy (claims 4-6), wherein engineered murine induced pluripotent stem cells (iPSCs) capable of attenuating inflammation through controlled release of an anti-inflammatory drug, interleukin-1 receptor antagonist (IL-1Ra) (Abstract). Pferdehirt teaches in response to IL-1α, cells produced high levels of IL-1Ra, which inhibited inflammatory signaling and protected tissue-engineered cartilage from proteoglycan degradation (Abstract). The IL-1Ra of Pferdehirt reads as an anti-inflammatory polypeptide (claim 9). The engineered iPSCs of Pferdehirt read as a genetically modified cell comprising the nucleic acid sequence of claim 1, as the lentiviral vector of Pferdehirt would incorporate the sequence into the cell’s genome (claim 11).
Regarding claim 8, Pferdehirt teaches an artificial gene circuit for controlled, cell-based delivery of biologic drugs, based on a nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-responsive synthetic promoter (Abstract).
Regarding claims 17-20 and 23, Pferdehirt teaches the development of self-regulating iPSCs that are capable of forming engineered cartilage for the replacement of diseased tissue and mitigating the inflammatory effects of IL-1α (p. 816). Cartilage cells express both TRPV4, PIEV01, and PIEV02 as evidenced by Nims. Nims teaches chondrocytes comprise TRPV4 (claims 18-19) and PIEZ01 and PIEZ02 (claim 23), which are mechanically sensitive ion channels (claim 17) (Nims, p. 2, 2nd column). Therefore, the cartilage cells of Pferdehirt would necessarily comprise the mechanically sensitive ion channels TRPV4, PIEV01, and PIEV02.
Regarding claim 24, Pferdehirt teaches the synthetic NF-kB-inducible promoter was designed to incorporate multiple NF-kB response elements that drive a target gene of interest, wherein, the synthetic promoter was developed containing five consensus sequences approximating the NF-kB canonical recognition motif based on genes that are upregulated by inflammatory challenge, to include Adamts5 (p. 810, Vector design). This reads as the promoter of the mechanically-responsive gene is an ADAMTS1 promoter.
Regarding claims 25 and 28, Pferdehirt teaches lentivirus-based gene therapy, wherein engineered murine induced pluripotent stem cells (iPSCs) capable of attenuating inflammation through controlled release of an anti-inflammatory drug, IL-1Ra (Abstract). The iPSCs of Pferdehirt read as genetically modified cell, wherein the therapeutic biologic nucleic acid molecule encodes for IL-1Ra (claim 25). The cells of Pferdehirt read as a genetically modified cell wherein the period of the therapeutic biologic (IL-1Ra) expression is modulated through the transcriptional regulatory nucleic acid molecule of a mechanically responsive gene (NF-kB) (claim 28).
Thus, the reference anticipates the subject matter of claims 1-6, 8-9, 11, 17-20, 23-25, and 28.
Claims 1-2, 4-6, and 8-10 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Van Der Sanden et al. (WO 2021/009684 A1, published 21 January 2021).
Regarding claims 1, 2, 8, and 10, Van Der Sanden teaches recombinant AAV (rAAV) virions for gene therapy for the treatment of arthritic disease, such as rheumatoid arthritis (RA) an inflammatory disease (Abstract and p. 1, lines 21-25 ). Van Der Sanden teaches an rAAV virion (viral vector) comprising a promoter operably linked to a nucleotide sequence encoding a gene product of interest, wherein the gene product of interest is an IL-1 inhibitor (therapeutic biologic) (p. 1, lines 37-38 and p. 2, lines 25-26). Van Der Sanden teaches wherein the IL-1 inhibitor is preferably the human IL-1 receptor antagonist (IL-1Ra), anakinra (p. 3, lines 1-5). Van Der Sanden teaches the rAAV virion wherein the promoter is an inducible promoter, preferably a NFkB responsive promoter or a COX2 (PTGS2) promoter (claims 2, 8, 10), among others (p. 22, lines 1-13). The PTGS2 promoter reads as a transcriptional regulatory nucleic acid sequence of a mechanically-responsive gene (claim 1).
Regarding claims 4-6, Van Der Sanden teaches an rAAV virion (viral vector) comprising a promoter operably linked to a nucleotide sequence encoding a gene product of interest, wherein the gene product of interest is an IL-1 inhibitor.
Regarding claim 9, Van Der Sanden teaches wherein the IL-1 inhibitor is preferably the human IL-1 receptor antagonist, anakinra (p. 3, lines 1-5). The human IL-1Ra reads as an anti-inflammatory polypeptide.
Thus, the reference anticipates the subject matter of claims 1-2, 4-6, and 8-10.
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.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Pferdehirt et al. (Tissue Engineering: Part A, Volume 25, Numbers 9 and 10, 2019, IDS ref.) as evidenced by Nims et al. (Sci. Adv. 2021; 7, published 27 January 2021, IDS ref.) as applied to claims 1-6, 8-9, 11, 17-20, 23-25, and 28 above, and further in view of Van Der Sanden et al. (WO 2021/009684 A1, published 21 January 2021).
Pferdehirt anticipate the subject matter of claims 1-6, 8-9, 11, 17-20, 23-25, and 28, and thus also, render them obvious.
Regarding claim 10, Pferdehirt do not teach wherein the promoter is the PTGS2 promoter.
However, Van Der Sanden teaches recombinant AAV (rAAV) virions for gene therapy for the treatment of arthritic disease, such as rheumatoid arthritis (RA) an inflammatory disease (Abstract and p. 1, lines 21-25 ). Van Der Sanden teaches an rAAV virion comprising a promoter operably linked to a nucleotide sequence encoding a gene product of interest, wherein the gene product of interest is an IL-1 inhibitor (p. 1, lines 37-38 and p. 2, lines 25-26). Van Der Sanden teaches wherein the IL-1 inhibitor is preferably the human IL-1 receptor antagonist, anakinra (p. 3, lines 1-5). Van Der Sanden teaches the rAAV virion wherein the promoter is an inducible promoter, preferably a NFkB responsive promoter or a COX2 (PTGS2) promoter, among others (p. 22, lines 1-13).
Therefore, it would have been obvious to one or ordinary skill in the art to utilize the PTGS2 promoter of Van Der Sanden with the vector of Pferdehirt with a reasonable expectation of success because Van Der Sanden and Pferdehirt both teach viral vector delivering the IL-1Ra therapeutic for treatment of inflammation and both teach the NFkB promoter for transgene expression. One would be motivated to utilize the PTGS2 promoter of Van Der Sanden with the vector of Pferdehirt because Van Der Sanden teaches both the NFkB and PTGS2 promoters for expression of the therapeutic transgene, which suggests the promoters would possess an equivalent function for transgene expression. Additionally, Van Der Sanden teaches expression of the transgene is controlled by a promoter which confers expression in cells of the joint, specifically connective tissue cells to include chondrocytes (p. 22, lines 36-39).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Relevant prior art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Rai et al. (PLoS ONE, October 2011, Volume 6, Issue 10)
Rai teaches regulated expression of therapeutic candidate gene(s) coupled with suitable scaffold(s) could potentially serve as a useful tissue-engineering tool to devise future treatment strategies for osteoarthritis. Rai teaches vectors expressing IL-4 utilizing the cytokine-responsive COX-2 promoter for transfecting chondrocytes.
Conclusion
No claims are allowed.
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/N.A.H./Examiner, Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631
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