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 .
Claims Status
Claim(s) 1-4, 6-8, 11-17, 19-30, and 32-34 is/are currently pending.
Applicant’s election of the Invention of Group I (claims 1, 4, 6-8, and 11-12) and Species election of: (1) a combination of 3 antibodies comprising: (a) a bNAb targeting V1/V2 loop of HIV-1 envelope glycoprotein comprising clone PG9, (b) a bNAb targeting V3 loop of the HIV-1 envelope glycoprotein comprising clone 10-1074, and (c) a bNAb targeting CD4-binding site (CD4bs) of the HIV-1 envelope glycoprotein comprising clone 3BNC117; and (2) a VL of SEQ ID NO: 11 and a VH of SEQ ID NO: 12, in the reply filed on 16Oct2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The species election of a VL of SEQ ID NO: 11 and a VH of SEQ ID NO: 12 is withdrawn. In view of the withdrawal of the restriction requirement as to the rejoined inventions, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claim(s) 2-3, 13-17, 19-30, and 32-34 is/are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.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 16Oct2025.
Claim(s) 1, 4, 6-8, and 11-12 is/are currently presented for examination on the merits.
Specification
The use of trade name(s) or mark(s) used in commerce (e.g., ATCC, ThermoFisher, Takara Biosciences, NanoDrop, BD Biosciences, FlowJo, GraphPad Prism, Sigma Aldrich, Millipore, GE healthcare, BioRad, Eagle Biosciences), has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Interpretation
Claim 12 recites “...comprising the VL having a polypeptide sequence of SEQ ID NO: 11, 15, or 19, the VH having a polypeptide sequence of SEQ ID NO: 12, 16, or 20, respectively...”. The term “respectively” is considered to mean that the VL and VH SEQ ID NOs are paired as follows: 11 and 12; 15 and 16; and 19 and 20.
Claim Objections
Claim 1 is objected to because of the following informalities: line 6 recites “……B cells and modified with a DNP moiety…” but should say “…B cells and is modified with a DNP moiety…”. Appropriate correction is required.
Claim 6 is objected to because of the following informalities: line 3 recites “…envelop glycoprotein gp160, gp 120, or gp41, or…” but should say “…envelope glycoprotein selected from gp160, gp[[ ]]120, and gp41[[,]]; or…”. Appropriate correction is required.
Claim 8 is objected to because of the following informalities: line 3 recites “…three or more bNAbs selected from the group.” but should say “…three or more bNAbs. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 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.
Claim(s) 1, 4, 6-8, and 11-12 is/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.
Regarding instant claim(s) 1 (and dependent claims 4, 6-8, 11-12), the phrase "…recognizes the at least one DNP-modified" lacks antecedent basis and renders the claim indefinite because it is unclear (1) whether the limitation(s) following the phrase “recognizes at least one DNP-modified ,” are part of the claimed invention and (2) it is unclear if the instant invention involves a CAR specific for DNP antigen, DNP-Ab antigen, or DNP-cell antigen (See MPEP § 2173). For the purposes of compact prosecution, the limitations are considered to mean “recognizes DNP antigen” and the “so as to target a cell expressing the marker associated with HIV or the malignant B cells” is not considered a part of the invention. This rejection may be overcome by amending claim 1 to clearly recite the limitations of the claimed invention; for example “…recognizes at least one DNP-modified antibody or cell, wherein the modified antibody or cell recognizes a marker on a target cell…”. Dependent claims 4, 6-8, and 11-12 can overcome this rejection by amending claim 1 as specified above.
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.
Claim(s) 1, 4 and 11 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2018/148224 A1 (hereinafter “WO224”).
Regarding instant claim(s) 1, 4, WO224 teaches a (1) CAR T cell specific for dinitrophenol (DNP), and (2) a DNP-modified antibody that binds to a marker on HIV, wherein the CAR specifically recognizes the DNP moiety of the DNP-modified anti-HIV marker antibody [e.g., title; abstract; background; ¶ 0034, 0037, 0039, 0067, 0107].
Regarding instant claim(s) 11, WO224 further teaches the CAR comprises an scFv (e.g., having both a VH and VL), a transmembrane domain, and an intracellular signaling domain [e.g., ¶ 0003, 0031-0032, 0035, 0085].
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(s) 6-8 is/are rejected under 35 U.S.C. 103 as being unpatentable over by WO 2018/148224 A1 (hereinafter “WO224”) as applied to claim 1 above, and further in view of US 2019/0381141 A1 (hereinafter “US141”).
The teachings of WO224 as recited above apply for claim 1.
WO224 does not expressly teach (1) the DNP-modified antibody binds HIV envelope glycoprotein gp160, gp120 or gp41, (2) that DNP-modified antibody is a broadly-neutralizing HIV-1 antibody (bNAb), wherein the bNAb is a PG9, 10-1074, or 3BNC117 antibody, or (3) that the combination therapy comprises three or more bNAbs.
Regarding instant claim(s) 6-8, US141 teaches HIV treatment compositions and methods comprising broadly neutralizing antibodies (bNAbs), and further teaches anti-HIV bNAbs including PG9, 10-1074, and 3BNC117 [e.g., title; abstract; ¶ 0026, 0047, 0051, 0053-0059, 0061, 0063, 0065, 0074-0075; claim 13]. US141 teaches bNAbs that bind gp160, gp120, or gp41 [e.g., ¶ 0012, 0014, 0060-0061, 0071-0072, 0074; claim 13]. US141 further teaches that given the potential escape of any single bNAb, it is likely that any clinical intervention would require combinations of multiple bNAbs to be effective [e.g., ¶ 0055-0058].
It would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to substitute the antibody of the DNP-modified antibody of the combination therapy as taught by WO224, with the anti-gp160, anti-gp120, anti-gp41, PG9 (clone), 10-1074 (clone), and/or 3BNC117 (clone) bNAbs as taught by US141, in the context of designing a combination therapy that targets HIV antigen(s). A PHOSITA would have been motivated to substitute antibody of the DNP-modified antibody of the combination therapy as taught by WO224, with the anti-gp160, anti-gp120, anti-gp41, PG9 (clone), 10-1074 (clone), and/or 3BNC117 (clone) bNAbs as taught by US141, because WO224 teaches the base combination therapy which comprises a DNP-modified antibody that targets HIV antigen, and US141 teaches bNAbs that are well known in the art to target specific HIV antigen(s). There would have been a reasonable expectation of success for a PHOSITA to substitute antibody of the DNP-modified antibody of the combination therapy as taught by WO224, with the anti-gp160, anti-gp120, anti-gp41, PG9 (clone), 10-1074 (clone), and/or 3BNC117 (clone) bNAbs as taught by US141 because WO224 teaches the base combination therapy which comprises a DNP-modified antibody that targets HIV antigen, and US141 teaches bNAbs that are well known in the art to target specific HIV antigen(s). This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
Further, it would have been obvious to a PHOSITA to modify the modified combination therapy comprising DNP-modified anti-HIV antigen bNAbs of WO224 and US141 (see above) to include the (1) that the combination therapy comprises multiple bNAbs as taught by US141, because WO224 and US141 teach the combination therapy comprising a DNP directed CAR and DNP-modified anti-HIV antigen bNAbs, and US141 further teaches that given the potential escape of any single bNAb, it is likely that any clinical intervention would require combinations of multiple bNAbs to be effective, which necessarily teaches three or more bNAbs. There is an expectation of success for a PHOPSITA to substitute the number of a DNP-modified anti-HIV antigen bNAb in the combination therapy as taught by WO224 and US141 with the multiple (e.g., includes 3 or more) bNAbs that target HIV, because WO224 and US141 teach the combination therapy comprising a DNP directed CAR and a DNP-modified anti-HIV antigen bNAb, and US141 further teaches that given the potential escape of any single bNAb, it is likely that any clinical intervention would require combinations of multiple bNAbs to be effective. This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Claim(s) 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over by WO 2018/148224 A1 (hereinafter “WO224”) as applied to claims 1 and 11 above, and further in view of US 2023/0068879 A1 (hereinafter “US879”).
The teachings of WO224 as recited above apply for claims 1 and 11.
WO224 does not expressly teach that the DNP binding domain of the CAR comprises a VL of instant SEQ ID NO: 19 and a VH of instant SEQ ID NO: 20.
Regarding instant claim(s) 12, US879 teaches an anti-DNP CAR comprising an scFv of SEQ ID NO: 9 which binds to DNP and comprises a VH and a VL that are the same as the instant claimed anti-DNP VH and VL of SEQ ID NOs: 20 and 19, respectively (see alignment below) [e.g., title; abstract; ¶ 0007, 0096, 0103; table 2; claim 66].
Alignment of instant claimed VL of SEQ ID NO: 19 and VH of SEQ ID NO: 20 with (Cancer treating CAR constructing anti-DNP scFv 1BAF VH-linker-VL, SEQ 9):
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It would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to substitute the DNP binding domain of the anti-DNP CAR T cell in the combination therapy taught by WO224, with the anti-DNP scFv binding domain of a CAR as taught by US879, in the context of designing or developing a universal CAR T cell that binds a DNP moiety. A PHOSITA would have been motivated to substitute the DNP binding domain of the anti-DNP CAR T in the combination therapy cell taught by WO224, with the anti-DNP scFv binding domain of a CAR as taught by US879, because both WO224 and US879 teach DNP directed CAR T cells, and US879 teaches the sequence for the antigen binding portion of the CAR that binds to DNP. There would have been a reasonable expectation of success for a PHOSITA to substitute the DNP binding domain of the anti-DNP CAR T of the combination therapy cell as taught by WO224, with the anti-DNP scFv binding domain of a CAR as taught by US879, because WO224 teaches combination therapy comprising an anti-DNP CAR, both WO224 and US879 teach DNP directed CAR T cells, and US879 teaches the sequence for the antigen binding portion of the CAR that binds to DNP. This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Free From the Prior Art
During the course of examination, the anti-DNP CAR T cell antigen binding domain comprising (1) a VL of SEQ ID NO: 11 and a VH of SEQ ID NO: 12; or (2) a VL of SEQ ID NO: 15 and a VH of SEQ ID NO: 16, were found to nonobvious over the prior art. Briefly, a sequence search of the prior art returned no 100% matches to either of the instant claimed VH and VL pairs (see closest prior art alignments below).
Alignment of anti-DNP VH (SEQ ID NO: 12) and VL (SEQ ID NO: 11) with WO2020205579-A1 (Anti-alpha CLL-1-alpha CD3 ScFv construct, SEQ ID 46):
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Alignment of anti-DNP VH (SEQ ID NO: 16) and VL (SEQ ID NO: 15) with WO2021148681-A1 (Anti-PP2Ac monovalent scFv antibody, SEQ ID 42):
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Conclusion
No claims are currently allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY M CHATTIN whose telephone number is (571)270-0646. The examiner can normally be reached T-F 0600-1600 PST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Wu can be reached at (571) 272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AMY M. CHATTIN/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643