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 .
Detailed Action
This action is in response to the papers filed May 11, 2026.
Claim Amendments
Applicant’s amendment to the claims filed 05/11/2026 is acknowledged.
Claims 1-2 and 73 are amended.
Claims 6-21, 23-28, 31-53, 55-65, 67-72, 78-79, 82-87, 94-104, 107-119 have been cancelled.
Claims 1-5, 22, 29-30, 54, 66, 73-77, 80-81, 88-93, 105-106, 120-121 are pending.
Claims 91-93, and 121 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Claims 1-5, 22, 29-30, 54, 66, 73-77, 80-81, 88-90, 105-106, and 120 are under examination.
Election/Restrictions
The following is a summary of the restriction/election requirements in the present application. See, the Restriction/Election mailed 07/30/2025.
In the reply filed 10/29/2025, Applicant elected without traverse the invention of Group 1, drawn to a method of treating multiple myeloma in a subject in need thereof, and the antigen-binding domain according to SEQ ID NO: 114.
The elected antigen-binding domain according to SEQ ID NO: 114 comprises the variable heavy chain according to SEQ ID NO: 116, the variable light chain according to SEQ ID NO: 119, and the CDR-H1 of SEQ ID NO: 97, the CDR-H2 of SEQ ID NO: 101, the CDR-H3 of SEQ ID NO: 103, the CDR-L1 of SEQ ID NO: 105, the CDR-L2 of SEQ ID NO: 107 and the CDR-L3 of SEQ ID NO: 108, and the CAR polypeptide according to SEQ ID NO: 19 comprises the elected antigen-binding domain according to SEQ ID NO: 114. The nonelected antigen-binding domains according to SEQ ID NOs: 126 and 128 each comprise the variable heavy chain according to SEQ ID NO: 125 and the variable light chain according to SEQ ID NO: 127.
Claims 91-93, and 121 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 10/29/2025.
Priority
The instant application 17/799,239 was filed on 08/11/2022. This application is a national stage of international application PCT/US2021/017737 filed 02/11/2021, claiming priority based on U.S. Provisional Application 62/975,731 filed 02/12/2020.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 05/11/2026 has been considered.
Withdrawal of Prior Rejections/Objections
Rejections and/or objections not reiterated from the previous Office action mailed 02/10/2026 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application. Applicant’s remarks filed 05/11/2026 have been carefully considered, but are moot in view of the new grounds of rejection, necessitated by amendment.
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 1-5, 22, 29-30, 54, 66, 73-77, 80-81, 88-90, 105-106, and 120 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.
This rejection is newly applied, necessitated by amendment.
Claims 1 and 2 recite a process of treating multiple myeloma (MM) comprising: “administering to a subject having MM a composition comprising engineered T cells expressing a chimeric antigen receptor (CAR) that targets B cell maturation antigen (BCMA)” and “the harvesting of the engineered T cells is carried out at a time when integrated vector can be detected in the genome but prior to achieving a stable integrated vector copy number (iVCN) per diploid genome.”
The process as claimed is found to be indefinite for the following reasons:
The limitation “the harvesting of the engineered T cells” lacks antecedent basis. No harvesting step is previously recited by the claims. Moreover, it is unclear from where the engineered T cells are harvested. For example, it is unclear if the engineered T cells are harvested from a previous cell culture not recited by the claims, or, considering that the antecedent basis of “the engineered T cells” is found in the administration step (i.e., “administering to a subject having MM a composition comprising engineered T cells”), if the engineered T cells are harvested from the subject having MM at a time following the administration step.
The claims recite harvesting at a time “when integrated vector can be detected in the genome but prior to achieving a stable integrated vector copy number (iVCN) per diploid genome.” However, the limitation of an “integrated vector” lacks antecedent basis. No integrating vector is previously recited by the claims, nor are the engineered T cells previously described as being transformed by an integrating vector. Moreover, it is unclear if the integrating vector encodes the CAR molecule recited in the administration step, or if the integrating vector encodes another polypeptide or any polypeptide at all.
The claims recite achieved a “stable” integrated vector copy number. The term “stable,” as claimed in claims 1-2, is a relative term which renders the claim indefinite. The term is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. In this case, the specification describes a “stable” integrated vector copy number as a term of degree without a defined standard for ascertaining the requisite degree. For example, the specification contemplates that, in some embodiments, the integration may be considered “stable” when the measured iVCN of a cell population is within about 20%, 15%, 10% or 5% of the total vector copy number (VCN) in the population. In other embodiments, a “stable” iVCN per diploid genome may be achieved when the iVCN peaks and/or remains unchanged for a period of time or unchanged within a tolerated error of about ±40%, ±35%, ±30%, ±25%, ±20%, ±15%, ±10%, ±5%, ±2%, ±1% or less than ±1% for a period of time. See, paragraphs 411 and 581. Accordingly, lacking a defined standard for ascertaining the requisite degree in both the claims and specification, one of ordinary skill in the art would not have been reasonably apprised of the metes and bounds as to the requirements for a “stable” integrated vector copy number in claims 1-2. For example, based on the evidence of record, it would be unclear whether infringement occurs when the measured iVCN of a cell population is within about 25% of the total VCN in the population.
For these reasons, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Dependent claims are included in the basis of the rejection because they do not correct the deficiencies of the claim upon which they depend.
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.
Claims 1-5, 22, 29-30, 54, 66, 73-77, 80-81, 88-90, 105-106, and 120 are rejected 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. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
This rejection is newly applied, necessitated by amendment.
Claims 1 and 2 recite a process of treating multiple myeloma (MM) comprising: “administering to a subject having MM a composition comprising engineered T cells expressing a chimeric antigen receptor (CAR) that targets B cell maturation antigen (BCMA)” and “the harvesting of the engineered T cells is carried out at a time when integrated vector can be detected in the genome but prior to achieving a stable integrated vector copy number (iVCN) per diploid genome.”
The antecedent basis for the limitation “the engineered T cells” in the harvesting step is found in the previously-recited administration step (i.e., “administering to a subject having MM a composition comprising engineered T cells”). Accordingly, claims 1-2 includes harvesting engineered T cells from the subject at a time when integrated vector can be detected in the genome but prior to achieving a stable integrated vector copy number (iVCN) per diploid genome. Sufficient written support for said limitation is not found in the specification as originally filed, and, thus, claims 1-2 are rejected under 35 U.S.C. 112(a) for reciting new matter, absent evidence to the contrary. Dependent claims are included in the basis of the rejection because they do not correct the deficiencies of the claim upon which they depend.
Claims 1-5, 22, 29-30, 54, 66, 73-77, 80-81, 88-90, 105-106, and 120 are rejected 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. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
This rejection is newly applied, necessitated by amendment.
Claims 1 and 2 recite a step of harvesting a population of engineered T cells “at a time when integrated vector can be detected in the genome but prior to achieving a stable integrated vector copy number (iVCN) per diploid genome.” The claims do not include a step of detecting the integrated vector or a step of measuring the iVCN in the cell population. Rather, the claims broadly embrace a harvesting step that is performed at a time after an integrated vector can be detected and before a stable iVCN per diploid genome is achieved, without performing the prerequisite steps of detecting the integrated vector or measuring the iVCN in the cell population. Accordingly, the claims are directed to an undisclosed genus of harvesting times functionally-described as being not too early (i.e., not prior to the time when integrated vector can be detected) and not too late (i.e., not after the time a stable iVCN per diploid genome is achieved).
An adequate written description of a genus of harvesting times, functionally-described as after an integrated vector can be detected and before a stable iVCN per diploid genome is achieved, requires more than a mere statement that it is part of the invention and reference to a potential method for determining it. What is required is a description of the prerequisite reagents and actions required to determine such a harvesting time satisfying the functional description. It is not sufficient to describe a genus of harvesting times solely by its desired biological property, i.e., after an integrated vector can be detected and before a stable iVCN per diploid genome is achieved, because disclosure of no more than that, as in the instant case, is simply a wish to know a priori the harvesting time, in any context within the metes and bounds of the claims, that satisfies the functional description. Thus, claiming any harvesting time that satisfies the functional description, without defining what means will do, or without performing the prerequisite detection and measurement steps, is not in compliance with the written description requirement.
The specification nominally discloses that the “harvesting is carried out at a time when integrated vector is detected in the genome but prior to achieving a stable integrated vector copy number (iVCN) per diploid genome.” See, e.g., par. 70. However, the specification contemplates a broad range of harvesting times that may or may not satisfy the functional description, e.g., from, at least, 2 hours to 3 days. See, paragraphs 411 and 581. This description indicates that the functionally-described harvesting time is not known a priori but rather may be variable across different cell cultures. Indeed, the working examples describe steps of measuring the iVCN and VCN only between a non-expanded cell population and an expanded cell population. See, paragraphs 723-726 and Figure 5A. Accordingly, the specification is not found to provide sufficient description for the claimed genus of harvesting times without performing the prerequisite detection and measurement steps, as instantly claimed.
Processes of harvesting engineered T cells which express an integrated vector encoding a CAR molecule are known in the art. For example, WO 2019/113557 A1 to Mujacic et al. describes a process of producing a population of engineered T cells comprising: introducing a CAR that targets BCMA into T cells, incubating the engineered T cells for 120 hours or less, and harvesting expanded population of engineered T cells. See, e.g., paragraphs 14, 34, 99, 264, 268, 291, 312. Another example, Yang et al. (2022) “Next-day manufacture of a novel anti-CD19 CAR-T therapy for B-cell acute lymphoblastic leukemia: first-in-human clinical study” Blood Cancer J. 12:104, 9 pages, describes a process of producing a population of engineered T cells comprising: introducing a CAR that targets CD19 into T cells, and harvesting the population of engineered T cells the next day without an expansion step. However, neither Mujacic nor Yang disclose whether or not their harvesting times satisfy the functional description in claims 1 and 2, and, based on applicant’s specification, one of ordinary skill in the art would not have known whether the references’ harvesting times meet the requirements of the instantly claimed invention in the absence of performing the prerequisite detection and measurement steps.
Accordingly, this limited information is not deemed sufficient to reasonably convey to one skilled in the art that the applicant is in possession of the undisclosed genus of harvesting times functionally-described as being not too early (i.e., not prior to the time when integrated vector can be detected) and not too late (i.e., not after the time a stable iVCN per diploid genome is achieved), without having to perform the prerequisite steps of detecting the integrated vector and measuring the iVCN in the cell population, at time the application was filed. Dependent claims are included in the basis of the rejection because they do not correct the deficiencies of the claim upon which they depend.
Conclusion
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 JAMES J GRABER whose telephone number is (571)270-3988. The examiner can normally be reached Monday-Thursday: 9:00 am - 4:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James D Schultz can be reached at (571)272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JAMES JOSEPH GRABER/Examiner, Art Unit 1631
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