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 .
Priority
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. Acknowledgment is made of applicants' claim for foreign priority to European application EP 20382792.8 filed on 09/07/2020. Certified copies of the foreign priority document(s) are present in the application file.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 07/13/2023 and 08/13/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claims 5-10, and 12-17 objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim should refer to other claims in the alternative only, and/or, cannot depend from any other multiple dependent claim. See MPEP § 608.01(n). Accordingly, the claims 5-10, 12-17 not been further treated on the 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.
Claims 15-17 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth 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.
Claims 15-17 describe use of a composition of claims 10 or 11 for a specific use, without reciting active steps. It is unclear from the wording of the claims as to what is being claimed besides the composition.
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 1, 3-4, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Soria-Juan et al (Front Immunol. 2019 Jun 4; hereinafter "Soria-Juan;" PTO-892) in view of Delenda et al (J Gene Med. 2004 Feb; hereinafter "Delenda;" See PTO-892).
Regarding claims 1, 3-4, and 11: Soria-Juan was directed to developing and evaluating a cost-effective, safe and personalized cell therapy approach for critical limb ischemia in Type 2 diabetes patients. Soria-Juan taught that “Targeting the CXCL12 and C-X-C chemokine receptor type 4 (CXCR-4) may improve the cell migration capacity of transplanted MSCs, and CXCL12 is also highly expressed in injured tissues and contributes to the recruitment of CXR4-positive cells. As a small proportion of MSCs express CXCR4 in culture, their capacity to migrate, and to respond to homing signals in damaged tissue may be reduced. Therefore, targeting CXCR4 may improve the migratory and therapeutic effects of MSCs. Within this context, we propose using MSCs modified to overexpress CXR4 and IL10 and/or IL7 (Generation 3 MSCs). Expression of the CXCR4 receptor will increase the migration of MSCs toward the inflammatory focus, while coexpression of the anti-inflammatory cytokine interleukin 10 (IL-10) and/or the anti-infectious cytokine interleukin 7 (IL-7) will increase the anti-inflammatory effect (IL-10) and even the anti-infective effect (IL-7).” (See Soria-Juan p. 12, col. 2, para 2). As such Soria-Juan established the desirability of co-expression of CXCR4 and IL-10 in MSC.
Delenda was directed to the use of lentiviral vectors (claim 11) for delivery of transgenes of interest. Delenda taught “co-expressing the transgene of interest with a reporter gene in order to follow the expression in bulk cell population” (Delenda S132, col. 2, last para). Delenda taught that “Transfer vector genomes contain all the cis-active sequences needed for packaging (ψ), reverse transcription (primer binding site, LTRs), integration (attL and attR integration sites) and transcription (5′-LTR or internal heterologous promoter), as well as the transgene of interest.“ (Delenda S128, col. 1, last para – col. 2, first para). It is further noted that Delenda taught codon optimization of transgenes (as required by claim 2) (See Delenda Figure 2). Delenda further taught “The improvement of transgene expression has also been facilitated by the addition of elements that act post-transcriptionally. The insertion of the post-transcriptional regulatory element (PRE) of the woodchuck (WPRE – as required by claims 3 and 4) or human (HPRE) hepatitis B viruses (HBVs) has substantially increased the levels of expression from HIV-1-derived vectors in a transgene-, promoter- and vector-independent manner.” (Delenda S128, col. 2, para 4).
A person of ordinary skill in the art in reading Soria-Juan would have realized importance of co-expression of CXCR4 and IL10 in MSC to improve migration and anti-inflammatory activity and would have been motivated to create a genetic cassette capable of co-expressing these two proteins to achieve the same functional outcome. Delenda taught that lentiviral vectors and other mammalian expression systems routinely included promoters and other elements such as WPRE elements and codon-optimization of transgenes themselves to achieve a stable and high-level transgene expression, as such the construction of two coding sequences is a predictable and well-known practice in the art. It would have been routine for a skilled artisan to employ bicistronic strategies as described in Delenda to co-express CXCR4 and IL-10 in a single vector, given the required therapeutic effect of Soria-Juan. The resulting construct would have been predictable and within routine capabilities of a skilled artisan.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Soria-Juan et al (Front Immunol. 2019 Jun 4; hereinafter "Soria-Juan;" PTO-892) in view of Delenda et al (J Gene Med. 2004 Feb; hereinafter "Delenda;" See PTO-892), and further in view of Inouye et al (Protein Expr Purif. 2015 May; hereinafter "Inouye;" See PTO-892); GenBank U59105, NM_003467; first available 1988; hereinafter "GenBank;" See PTO-892) and Kotenko et al (EMBO J. 1997 Oct 1; hereinafter "Kotenko;" See PTO-892).
Regarding claim 2: The teachings of Soria-Juan in view of Delenda are set forth above. It is submitted that codon optimization for mammalian cell expression was known in the art as taught by Delenda, enumerated above. Further, Inouye taught a technique of codon optimization using “design rule for preparing codon-optimized genes for expression it in mammalian cells by selection of only preferentially used human codons” (See Inouye, p. 47, col. 1, para 1). It is also submitted that the sequences of CXCR4 and IL10 were previously known (See Kotenko and GenBank). The resulting nucleotide sequences (SEQ ID NO: 1 and SEQ ID NO: 3); being codon optimized variants encoding the same known proteins would have been predictable products of routine optimization and therefore obvious, absent evidence of unexpected results.
Conclusion
No claim is free of art.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAGAMYA VIJAYARAGHAVAN whose telephone number is (703)756-5934. The examiner can normally be reached 9:00a-5:00p.
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/JAGAMYA NMN VIJAYARAGHAVAN/Examiner, Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633
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