DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s response and amendments received September 14, 2026 are acknowledged.
Claims 2, 15, and 18 have been canceled.
Claims 1, 3-14, 16, and 17 have been amended.
Claims 1, 3-14, 16, 17, 19, and 20 are pending in the instant application.
Claims 19 and 20 stand withdrawn from consideration as being drawn to a nonelected invention. See 37 CFR 1.142(b) and MPEP § 821.03, for reasons of record set forth in the Office Action mailed February 26, 2026.
Claims 1, 3-14, 16, and 17 are under examination in this office action.
Claim Objections
The objection to claim 1 for the recitation of an abbreviation of a term not defined in the claim has been withdrawn in view of applicant’s claim amendments received September 14, 2026.
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.
The rejection of claims 4-6, 8, 9, 11, 12, and 14-18 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite has been withdrawn in view of applicant’s claim amendments received September 14, 2026 which reasonably address the issues raised in the prior office action.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
The rejection of claims 1-18 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement has been withdrawn in view of applicant’s claim amendments received September 14, 2026.
The rejection of claims 1-18 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement has been withdrawn in view of applicant’s claim amendments received September 14, 2026.
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.
The rejection of claims 1-3, 7-12, 15-18 under 35 U.S.C. 102(a)(1) as being anticipated by Epstein et al. (WO 2019/067425) has been withdrawn in view of applicant’s claim amendments received September 14, 2026.
The rejection of claims 1-18 under 35 U.S.C. 102(a)(1) as being anticipated by June et al. (US 9,365,641) has been withdrawn in view of applicant’s claim amendments received September 14, 2026.
The following are new grounds of rejection necessitated by applicant’s claim amendments received September 14, 2026
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.
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, 3-14, 16, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over June et al. (US 9,365,641, of record) in view of Gill et al. (WO 2017/019848).
June et al. disclose chimeric antigen receptors that bind fibroblast activation protein (FAP) as well as cells expression such constructs (see entire document, particularly the abstract and claims). Notably such constructs are disclosed as comprising a scFv that binds FAP, a CD8 Hinge, a CD8 transmembrane, intracellular CD28 and intracellular CD3zeta domains (see particularly Figure 11D as well as lines 27-32 of column 4 and example 3). June et al. disclose anti-FAP CAR which comprise the VH of instant SEQ ID NO:10 and the VL of instant SEQ ID NO:11 (see sequence alignments previously provided and note that the ‘641 patent originally published as US 2014/0099340). CAR constructs are disclosed as being lentivirally transduced into the cells of June et al. (see particularly columns 38-40 and examples 1 and 3). These teachings differ from what is presently claimed in that the cells expressing the FAP binding CAR of June et al. are not disclosed as being macrophages, monocytes or dendritic cells.
Gill et al. disclose that by expressing a chimeric antigen receptor in a monocyte, macrophage or dendritic cell, the modified cell is recruited to the tumor microenvironment where it acts as a potent immune effector by infiltrating the tumor and killing the target cells (see entire document, particularly the abstract, claims and page 2). Notably, FAP is disclosed as a target of the CAR expressed on the cells of Gil et al. (see most particularly page 34). The cells of Gill et al. are disclosed as offering the advantageous properties of phagocytosis, targeted cellular toxicity, antigen presentation, and cytokine secretion (see particularly page 56).
Therefore, it would have been obvious to a person of ordinary skill in the art to transduce macrophages with the anti-FAP CAR constructs of June et al. Artisans would have been motivated to do so in order to gain the advantages of phagocytosis, targeted cellular toxicity, antigen presentation, and cytokine secretion as compared to T cells as was taught by Gill et al.
Claims 1, 3-14, 16, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over June et al. (US 9,365,641, of record) in view of O’Neill et al. (WO 2017/025944).
June et al. disclose chimeric antigen receptors that bind fibroblast activation protein (FAP) as well as cells expression such constructs (see entire document, particularly the abstract and claims). Notably such constructs are disclosed as comprising a scFv that binds FAP, a CD8 Hinge, a CD8 transmembrane, intracellular CD28 and intracellular CD3zeta domains (see particularly Figure 11D as well as lines 27-32 of column 4 and example 3). June et al. disclose anti-FAP CAR which comprise the VH of instant SEQ ID NO:10 and the VL of instant SEQ ID NO:11 (see sequence alignments previously provided and note that the ‘641 patent originally published as US 2014/0099340). CAR constructs are disclosed as being lentivirally transduced into the cells of June et al. (see particularly columns 38-40 and examples 1 and 3). These teachings differ from what is presently claimed in that the cells expressing the FAP binding CAR of June et al. are not disclosed as being macrophages, monocytes or dendritic cells.
O’Neill et al. disclose the generation of macrophages that express chimeric antigen receptors, and their administration to treat cancer (see entire document, particularly the abstract, claims and page 22). They disclose that macrophages expressing CARs are advantageous as compared to T cells expressing CARs as they lack persistence which reduced chronic activation the in the presence of low concentration of the antigenic target and since macrophages do not participate in cytokine storms they do not have that serious side effect seen in CAR-T therapies (see page 23).
Therefore, it would have been obvious to a person of ordinary skill in the art to transduce macrophages with the anti-FAP CAR constructs of June et al. Artisans would have been motivated to do so in order to gain the advantages of reduced cytokine storm side effects when used for therapy as compared to CAR T cells as was taught by O’Neill et al.
Claims 1, 3, 7-14, 16, and 18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Epstein et al. (WO 2019/067425, of record) in view of Gill et al. (WO 2017/019848).
Epstein et al. disclose chimeric antigen receptors that bind fibroblast activation protein (FAP) as well as cells expression such constructs (see entire document, particularly the abstract and claims). The FAP binding domain is disclosed as being a scFv that binds FAP (see for example page 22). Further, such constructs are disclosed as comprising CD8 transmembrane domains as well as CD28 and CD3zeta cytoplasmic domains (see for example pages 23-26 and the paragraph spanning pages 35 and 36 in working example 1). Such FAP constructs are disclosed as being delivered by lentiviruses (see for example pages 13 and 36). These teachings differ from what is presently claimed in that the cells expressing the FAP binding CAR of Epstein et al. are not disclosed as being macrophages, monocytes or dendritic cells.
Gill et al. disclose that by expressing a chimeric antigen receptor in a monocyte, macrophage or dendritic cell, the modified cell is recruited to the tumor microenvironment where it acts as a potent immune effector by infiltrating the tumor and killing the target cells (see entire document, particularly the abstract, claims and page 2). Notably, FAP is disclosed as a target of the CAR expressed on the cells of Gil et al. (see most particularly page 34). The cells of Gill et al. are disclosed as offering the advantageous properties of phagocytosis, targeted cellular toxicity, antigen presentation, and cytokine secretion (see particularly page 56).
Therefore, it would have been obvious to a person of ordinary skill in the art to transduce macrophages with the anti-FAP CAR constructs of Epstein et al. Artisans would have been motivated to do so in order to gain the advantages of phagocytosis, targeted cellular toxicity, antigen presentation, and cytokine secretion as compared to T cells as was taught by Gill et al.
Claims 1, 3, 7-14, 16, and 18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Epstein et al. (WO 2019/067425, of record) in view of O’Neill et al. (WO 2017/025944).
Epstein et al. disclose chimeric antigen receptors that bind fibroblast activation protein (FAP) as well as cells expression such constructs (see entire document, particularly the abstract and claims). The FAP binding domain is disclosed as being a scFv that binds FAP (see for example page 22). Further, such constructs are disclosed as comprising CD8 transmembrane domains as well as CD28 and CD3zeta cytoplasmic domains (see for example pages 23-26 and the paragraph spanning pages 35 and 36 in working example 1). Such FAP constructs are disclosed as being delivered by lentiviruses (see for example pages 13 and 36). These teachings differ from what is presently claimed in that the cells expressing the FAP binding CAR of Epstein et al. are not disclosed as being macrophages, monocytes or dendritic cells.
O’Neill et al. disclose the generation of macrophages that express chimeric antigen receptors, and their administration to treat cancer (see entire document, particularly the abstract, claims and page 22). They disclose that macrophages expressing CARs are advantageous as compared to T cells expressing CARs as they lack persistence which reduced chronic activation the in the presence of low concentration of the antigenic target and since macrophages do not participate in cytokine storms they do not have that serious side effect seen in CAR-T therapies (see page 23).
Therefore, it would have been obvious to a person of ordinary skill in the art to transduce macrophages with the anti-FAP CAR constructs of Epstein et al. Artisans would have been motivated to do so in order to gain the advantages of reduced cytokine storm side effects when used for therapy as compared to CAR T cells as was taught by O’Neill et al.
Claims 9, 11, 12, and 14 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.
Dependent claims 9, 11, 12, and 14 all ultimately refer back to independent claim 1, which recites a cell expressing a chimeric antigen receptor (CAR) and thus the claims read upon cells that express a non-naturally occurring polypeptide fusion protein. Claim 9 recites that the CAR comprises a CD28 intracellular domain that has the amino acid sequence of SEQ ID NO:14 or the CD28 intracellular domain has a nucleic acid sequence shown in SEQ ID NO:15. Thus, what is applicant claiming via the recitation of a polynucleotide sequence as part of receptor that very clearly is a fusion protein? Is applicant claiming a protein-nucleic acid hybrid molecule or is applicant simply trying to say that the polypeptide sequence present in the claimed protein is encoded by the recited polynucleotide sequence? Claims 11, 12, and 14 are directed to different subsequences but present the same issue of a fusion construct having both an attached polypeptide sequence and an attached polynucleotide sequence. Given that instant claim 6 was amended to recite “encoded by” language, it appears that such an interpretation is also applicable to the instant recited nucleic acid SEQ ID numbers, but applicant is reminded that the claims are limited by what they actually recite, not what artisans might guess they mean. Appropriate amendments to clarify what is being claimed, perhaps similar to the language presented in instant claim 6, are likely to be beneficial in removing this rejection.
No claims are allowable.
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 Michael Szperka whose telephone number is (571)272-2934. The examiner can normally be reached Monday-Friday 8:30-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Michael Szperka
Primary Examiner
Art Unit 1641
/MICHAEL SZPERKA/Primary Examiner, Art Unit 1641
