DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant’s election without traverse of the invention of Group I (claims 1-10) and the species of mannosylated polyethyleneimine in the reply filed on 04/20/2026 is acknowledged.
Claims 12-21 are withdrawn from further consideration by the Examiner under 37 C.F.R. § 1.142(b) as being drawn to nonelected inventions.
Claims 1-10 are presently under consideration.
3. 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.
4. Claims 1-10 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
(i) Claim 1 is indefinite, because the meaning of the term “CAR macrophage” is unknown. A CAR is a protein, i.e. a product, and a macrophage is a cell, i.e. also a product; the identity of the presumed combination product defined by reference to tow other products is unknown.
(ii) Claim 1 is further indefinite because it is subject to alternative interpretations due to inconsistent use of conjunctions. A complex comprising “(A) a plasmid” and “(B) a carrier” and/or “(C) a CAR macrophage” may be understood as:
Interpretation-1: either (A+B+C) or (A+B) or (C);
Interpretation-2: (A) + any one of (B), (C), and (B+C).
One of the embodiments the claim reads on is a composition or complex comprising “CAR macrophage” alone.
(iii) Claim 1 is further indefinite, because it is unclear whether the “CAR macrophage” is comprised by both the composition and the complex, or by the composition but not the complex.
(iv) Claim 2 is indefinite in the recitation of the phrase “composition according to claim 1, wherein the chimeric antigen receptor is specifically bound to an antigen” because, according to the phrase, the antigen is also a part of the composition, which appears to be inconsistent with the context of the claims.
(v) Claim 5 is indefinite, because the recitation of “the non-viral carrier cationic molecule” lacks proper antecedent basis in the base claim.
(vi) Claim 6 is indefinite in the recitation of “transposase plasmid,” because the meaning of the expression is unknown. For examination purposes, it is provisionally assumed that the expression is intended to indicate a plasmid encoding a transposase, although it is noted that the examiner has not made a determination whether the specification as-filed provides adequate support under 35 U.S.C. 112(s) for such claim limitation.
(vii) Claim 7 is indefinite because of the inconsistency of the constituents of the complex prepared in claim 7 (plasmid DNA, non-viral carrier and transposase plasmid) and the complex of claim 1 on which claim 7 depends (plasmid DNA, non-viral carrier and/or CAR macrophage).
(viii) Claim 9 is indefinite in the recitation of plasmid DNA which “includes” a polypeptide (CD8 hinge region, etc.), where it appears that the intended meaning was plasmid DNA which “encodes” the recited polypeptides.
It is further noted that use of the conjunction “or” in listing CAR domains limits the claim to any single domain and excludes combinations of domains.
(ix) Claim 10 is indefinite in the recitation of a chimeric antigen receptor “is” an scFv, etc., where it appears that the intended meaning was a receptor which “comprises” the recited components.
(x) Claims 2-9 are indefinite, because they encompass the indefinite limitations of the claim(s) on which they depend.
In view of the above, a person of ordinary skill in the art cannot unequivocally interpret the metes and bounds of the claims so as to understand how to avoid infringement. Applicant is reminded that any amendment must point to a basis in the specification so as not to add New Matter. See MPEP 714.02 and 2163.06.
5. 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)(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.
6. Claims 1-2 and 4-10 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Akahoshi et al. (20210246424, of record).
As pointed out in the previous office action, Akahoshi teaches CAR DNA plasmid-encapsulating carrier (e.g. [0224] - [0238]), i.e. a complex of plasmid DNA encoding a CAR and a non-viral carrier, thereby anticipating instant claim 1.
The CAR comprises an scFv specific to CD19, CD22, CD30, CD33, CEA, Her2/neu, MUC1 or VEGFR2 (e.g. [0084]-[0085]), thereby anticipating instant claim 2.
The carrier comprises lipid particles (i.e. liposomes) containing PEG-cholesterol (e.g. [0225] ), thereby anticipating instant claims 4 and 8.
The DNA further encodes a transposase gene (e.g. [0025]), thereby anticipating instant claims 6 and 7.
The CAR contains CD28 transmembrane domain, CD28 costimulatory domain, and CD3 zeta signaling domain (e.g. [0088]-[0090]), thereby anticipating instant claims 9-10.
Claim 5 is included in the rejection, because it recites a broad range of N/P ratios, and Akahoshi teaches a variety of ratios of complex components (e.g. the Examples), i.e. the values within the recited range are present in, or would be at once envisaged in view of, Akahoshi’s teachings.
7. 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 of this title, 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.
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.
8. Claims 1 and 3 are rejected under 35 U.S.C. 103 as being unpatentable over Akahoshi et al. (20210246424, of record) in view of Xiao et al. (US 20210060069).
As addressed in section 6 above, Akahoshi teaches a composition within the scope of instant claim 1. Akahoshi further teaches including additional ingredients in the carrier complex, in particular cytokines (e.g. [0118]).
Although Akahoshi does not specifically exemplify including IFNγ-coding sequences, it was appreciated by those of ordinary skill in the art before the effective filing date of the claimed invention that introducing cytokine-encoding sequences, particularly IFNγ, together with CAR-encoding sequences into immune cells increases their therapeutic potency, as taught, for example, by Xiao at [0213]. This would have provided both the motivation and the expectation of success to those of ordinary skill in the art before the effective filing date of the claimed invention to combine IFNγ-coding sequence with Akahoshi’s CAR-encoding sequence.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
9. The following prior art references, which teach various aspects of the claimed invention, are cited of record but not presently relied upon. Collectively, the teachings highlight the knowledge in the art before the effective filing date of the claimed invention that CAR-expressing macrophages represent a promising modality of cancer therapy, and that mannose-containing non-viral transfection reagents such as mannosylated polyethyleneimine can be used for selective in vivo transfection of macrophages, which offers multiple advantages.
US Pat Pub. No. 20170151281
US Pat Pub. No. 20210128485
US Patent No.6420176
Diebold et al. (1999) Mannose Polyethylenimine Conjugates for Targeted DNA Delivery into Dendritic Cells. The Journal of Biological Chemistry, 274: 19087-19094.
Chen et al. (2021) Harnessing and Enhancing Macrophage Phagocytosis for Cancer Therapy. Front. Immunol. 12:635173, 1-16.
Hu et al. (2014) Synthesis of Mannosylated Polyethylenimine and Its Potential Application as Cell-Targeting Non-Viral Vector for Gene Therapy. Polymers 6: 2573-2587.
Jiang et al. (2009) Mannosylated chitosan-graft-polyethylenimine as a gene carrier for Raw 264.7 cell targeting. International Journal of Pharmaceutics 375 (2009) 133–139.
Klichinsky et al. (2020) Human chimeric antigen receptor macrophages for cancer immunotherapy. Nature Biotechnology 38: 947–953.
Sylvestre et al. (2020) Progress on Modulating Tumor-Associated Macrophages with Biomaterials. Adv. Mater. 32: 1902007, 1-19.
Zhang et al. (2019) Genetic programming of macrophages to perform anti-tumor functions using targeted mRNA nanocarriers. Nature Communications 10: 3974, 1-16.
Zhang et al. (2020) Pluripotent stem cell‑derived CAR‑macrophage cells with antigen‑dependent anti‑cancer cell functions. J Hematol Oncol. 13:153, 1-5.
10. Conclusion: no claim is allowed.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to ILIA I OUSPENSKI whose telephone number is (571)272-2920. The examiner can normally be reached 9 AM - 5:30 PM.
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/ILIA I OUSPENSKI/ Primary Examiner, Art Unit 1644
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