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 .
The claims dated 6/5/2026 are under consideration.
The amendments and arguments presented in the papers filed 6/5/2026 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 3/10/2026 listed below have been reconsidered as indicated.
a) The amendments to the specification are acknowledged.
b) The rejections of claims 1, 13, 14, 15, 16, 18, 20, 21 and 39 under 35 U.S.C. 101 because the claimed invention is directed to judicial exceptions without significantly more are rendered moot in view of the cancellation of the claims and are withdrawn.
c) The rejections of claims 14, 18, 21, 32 and 36 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, are withdrawn as being render moot in view of cancellation of the claim or in view of the amendment to the claim.
d) The rejections of claim(s) 1, 13, 14, 15, 16, 18, 20, 21, 24, 25, 26, 27, 28, 29, 30, 31, 32, 36 and 39 under 35 U.S.C. 103 as being unpatentable over Liu (Nature Communications. 2020. 11:5902, 14 pages) in view of Bell (Frontiers in Immunology. 2021. 12:Article 684642, 16 pages) are withdrawn as being rendered moot in view of the cancellation of the claims.
The Examiner’s responses to the Remarks regarding issues not listed above are detailed below in this Office action.
New and Modified grounds of rejection necessitated by amendment are detailed below and this action is made FINAL.
Priority
The present application claims benefit to US provisional applications: 63/386,411 (filed 12/7/2022); and 63/381,435 (filed 10/28/2022).
Priority is recognized.
Information Disclosure Statement
The listing of references in the specification or the citation of references throughout the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892 or on a submitted IDS, they have not been considered.
Claim Objections
Claim 36 is objected to because of the following informalities: the claim recites some elements multiple times, either directly or indirectly. For example, the term “CS-1” and “SLAMF7” and “human telomerase reverse transcriptase” and “telomerase” each refer to the same molecule, respectively. The term “BCMA” and “GD2” are each recited multiple times. 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 24-32 and 36 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 claim 24, the claim recites “the control value” in the second to last line. The recitation lacks proper antecedent basis in view of the amendments to the claims.
Claims 25-32 and 36 depend from claim 24 and are rejected for the same reason.
Regarding claims 30 and 31, it is unclear based on the use of the passive voice if the claim is intended to require an alternative conditional active method step of “administering the cell therapy product without the combination therapy” if the conditions specified in the claims are satisfied.
Regarding claim 36, the claim recites “e.g., plasma cell dyscrasia, solitary myeloma, solitary plasmacytoma, extramedullary plasmacytoma, and multiple plasmacytoma”. the phrase “e.g.”, which is equivalent to "for example", renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Response to the traversal of the 112(b) rejections
The Remarks argue the amendments address the prior 112(b) rejections (p. 8-9).
The claims remain rejected for the reasons provided above. The arguments are moot in regards to the above rejections.
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.
Claim(s) 24-32 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Liu (Nature Communications. 2020. 11:5902, 14 pages).
The following are new rejections necessitated by the amendments to the claims and in view of the following claim interpretation for claim 24.
Amended claim 24 is drawn to a method for determining whether a patient with a malignancy should be administered an effective dose of a cell therapy product and a combination therapy; however, the active method steps do not explicitly require making any determination regarding the patient. MPEP 2111.02 states:
If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention's limitations, then the preamble is not considered a limitation and is of no significance to claim construction.
Accordingly, the claim language of "a method for determining whether a patient with a malignancy should be administered an effective dose of a cell therapy product and a combination therapy" merely sets forth the intended use or purpose of the claimed methods, but does not limit the scope of the claims. The claims are given the broadest reasonable interpretation as explicitly requiring:
measuring a gene expression level of at least one gene selected from the group consisting of Interlukin-4 (IL-4) and HLA-DQB1 in the cell therapy product.
Claim 24 further includes a step of “administering the effective dose of the cell therapy product and the combination therapy”; however, the step is conditioned on the premise “if the gene expression level of the at least one gene is above the control value for the at least one gene”. Thus, the “administering” step is not required in all embodiments in particular in those in which gene expression level of the at least one gene is measured as not being above the control level, as it is noted the claim does not require measuring or observing any particular level of gene expression relative to a control level.
Regarding claim 24, Liu teaches measuring gene expression of IL-4 in a “cell therapy products” identified T9 CAR-T cells and/or T1 CAR-T cells (Fig. 1e).
Liu teaches the T9 CAR-T cells secrete fewer IL4 molecules than T1 CAR-T cells (p. 2 of 14, right column; and Fig. 1e). Liu further teaches that T9 CAR-T cells have decreased apoptosis with hyperproliferative capacity (p. 2 of 14, right column), demonstrate less exhaustion (p. 4 of 14, left column; and p. 6 of 14, left column) and have strong antitumor activity in vivo (p. 4 of 14, right column).
Thus, Liu teaches a step in which IL-4 gene expression is measured and observed to be below a control level represented by the T1 CAR-T cells. Liu anticipates embodiments in which the “administering” step is not performed because the condition of observing “the gene expression level of the at least one gene is above the control value for the at least one gene” is not satisfied.
Regarding claim 25, Liu teaches measuring the expression of IL4 prior to administration (p. 2 of 14, right column; Fig. 1e; p. 2 of 14, right column; p. 6 of 14, left column; and p. 4 of 14, right column).
Regarding claims 26 and 27, the claims further describe an embodiment when a cell therapy product and combination therapy are administered. The claims broadly encompass embodiments in which the “administering” step is not performed because the condition of observing “the gene expression level of the at least one gene is above the control value for the at least one gene” is not satisfied. Thus, claims 26 and 27 are anticipated for the same reason as claim 24. It is noted the claim 27 does not limit the claim to measuring the gene expression of HLA-DQB1 and broadly provides relevant information.
Regarding claims 28 and 29, the claim further limits the combination therapy but the “administering” remains dependent on observing “the gene expression level of the at least one gene is above the control value for the at least one gene”. Thus, claims 28 and 29 anticipated for the same reason as claim 24.
Regarding claims 30 and 31, the claims further describe when a cell therapy product and combination therapy are administered. The claims broadly encompass embodiments in which the “administering” step is not performed because the condition of observing “the gene expression level of the at least one gene is above the control value for the at least one gene” is not satisfied. Thus, claims 30 and 31 are anticipated for the same reason as claim 24. It is noted the claim 31 does not limit the claim to measuring the gene expression of HLA-DQB1 and broadly provides relevant information.
Regarding claim 32, Liu teaches the CAR-T cells recognize CD19 (p. 2, Human IL9-secreting CAR-T cells display distinct cytokine expression profiles).
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) 24, 25, 26, 27, 28, 29, 30, 31, 32 and 36 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liu (Nature Communications. 2020. 11:5902, 14 pages; previously cited) in view of Bell (Frontiers in Immunology. 2021. 12:Article 684642, 16 pages; previously cited) and Lindo (Frontiers in Immunology. 2021. 11:618387, 14 pages).
The following are new rejections necessitated by the amendments to the claims and in view of the following claim interpretation for claim 24.
Amended claim 24 is drawn to a method for determining whether a patient with a malignancy should be administered an effective dose of a cell therapy product and a combination therapy; however, the active method steps do not explicitly require making any determination regarding the patient. MPEP 2111.02 states:
If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention's limitations, then the preamble is not considered a limitation and is of no significance to claim construction.
Accordingly, the claim language of "a method for determining whether a patient with a malignancy should be administered an effective dose of a cell therapy product and a combination therapy" merely sets forth the intended use or purpose of the claimed methods, but does not limit the scope of the claims. The claims are given the broadest reasonable interpretation as requiring:
measuring a gene expression level of at least one gene selected from the group consisting of Interlukin-4 (IL-4) and HLA-DQB1 in the cell therapy product.
Claim 24 further includes a step of “administering the effective dose of the cell therapy product and the combination therapy”; however, the step is conditioned on “if the gene expression level of the at least one gene is above the control value for the at least one gene”. Thus, the “administering” step is not required in all embodiments in particular in those in which gene expression level of the at least one gene is measured as not being above the control level, as it is noted the claim does not require measuring or observing any particular level of gene expression relative to a control level.
Regarding claims 24, 28 and 29, Liu teaches measuring gene expression of IL-4 in a “cell therapy products” identified as T9 CAR-T cells and T1 CAR-T cells (Fig. 1e).
Liu teaches the T9 CAR-T cells secrete fewer IL4 molecules than T1 CAR-T cells (p. 2 of 14, right column; and Fig. 1e). Thus, relative to T9 CAR-T cells, T1 CAR-T cells secrete more IL4 molecules.
Liu further teaches that T9 CAR-T cells have decreased apoptosis with hyperproliferative capacity (p. 2 of 14, right column), demonstrate less exhaustion (p. 4 of 14, left column; and p. 6 of 14, left column) and have strong antitumor activity in vivo (p. 4 of 14, right column). Thus, relative to T9 CAR-T cells, T1 CAR-T have more apoptosis, hypoproliferative capacity, more exhaustion and less antitumor activity in vivo.
Bell teaches in the context of cancer and CAR T cells, IL-4 i is largely immunosuppressive (p. 3 of 16, left column). Bell further describes is it known that IL-4 producing T cells are less effective in controlling tumor growth (p. 3 of 16, left column).
Lindo teaches that it was known that in solid tumors IL-4 is a major contributor towards immunosuppression and neutralization of IL-4 using monoclonal antibodies has been shown to improve T-cell trafficking to tumors and T-cell-mediated antitumor functions (p. 9).
It would have been prima facie obvious at the time of filing to have administered T1 CAR-T cells with an IL-4 monoclonal antibody in order to neutralize IL-4 in order to improve T-cell trafficking to tumors and T-cell-mediated antitumor functions in view of Bell and Lindo.
Regarding claim 25, Liu teaches measuring the expression of IL4 prior to administration (p. 2 of 14, right column; Fig. 1e; p. 2 of 14, right column; p. 6 of 14, left column; and p. 4 of 14, right column).
Regarding claim 26, the claim sets forth gene expression levels relative to the control value. It would have been prima facie obvious to the ordinary artisan to have optimized the relationship between the measured gene expression level of IL-4 and the control value. Thus, the condition of claim 26 is rendered obvious as being a condition that may be achieved via routine optimization.
Regarding claim 27, the claim provides information regarding HLA-DQB1, but not specifically require measuring the expression level of HLA-DQB1. Claim 27 is rendered obvious for the same reason as claim 24 above.
Regarding claim 30, it would have been prima facie obvious to have administered the T9 CAR-T cells alone, without an IL-4 antibody, because the T9 CAR-T cells secrete lower levels of IL-4 and have decreased apoptosis with hyperproliferative capacity (p. 2 of 14, right column), demonstrate less exhaustion (p. 4 of 14, left column; and p. 6 of 14, left column) and have strong antitumor activity in vivo (p. 4 of 14, right column) .
Regarding claim 31, the claim provides information regarding HLA-DQB1, but not specifically require measuring the expression level of HLA-DQB1. Claim 31 is rendered obvious for the same reason as claim 24 above.
Regarding claim 32, Liu teaches the CAR-T cells recognize CD19 (p. 2, Human IL9-secreting CAR-T cells display distinct cytokine expression profiles).
Regarding claim 36, it would have been prima obvious to the ordinary artisan that CAR-T cells, which is a therapy for cancer, would be administered to subjects diagnosed as having cancer. In particular the CAR-T cells of Liu are specific for Acute Lymphoblastic Leukemia (ALL) cells, e.g., NALM6 tumor cells.
Claim 32 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984).
The following is a new rejection necessitated by the amendments to the claim. Previously the claim recited “the target antigen is a tumor antigen, preferably selected from a tumor associated surface antigen, such as 5T4…”. The previous exemplary language was interpreted as not setting forth a list of specific “tumor antigens” but rather a collection of “target antigens”. The claim now specifies the collection of targets are “tumor antigens”.
A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of claim 32 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: the Markush is in regards to a “tumor antigen” selected from the recited list. The list includes CD8, HIV-1 gp41, Lassa Virus-specific antigen HIV-specific antigen and Influenza Virus-specific antigen as “tumor antigens”. There is no evidence that tumors express any of these molecules as “tumor antigens”. Thus, these species do not share a common structure or use with the other species of the “tumor antigen” Markush grouping.
It is also noted that the claim includes the term “and” in multiple places, e.g., “survivin and telomerase, (EDA) and extra domain B”, “fibronectin and the A1 domain” and “HIV-specific antigen and GPC3”. It is suggested the claim be amended to clarify where species is represented by a group of molecules versus when the last two members of the Markush are being recited.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Conclusion
No claims allowed.
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 JOSEPH G DAUNER whose telephone number is (571)270-3574. The examiner can normally be reached 7 am EST to 4:30 EST with second Fridays Off.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston Shen can be reached at 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOSEPH G. DAUNER/Primary Examiner, Art Unit 1682
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