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 .
Application Status
The amended claims filed April 8, 2026 are acknowledged. Claims 1-21, 24, and 29-30 are canceled. Claims 22-23 and 25 are amended. Claims 31-47 are newly added.
Claims 22-23, 25-28, and 31-47 are pending and under examination herein.
WITHDRAWN OBJECTIONS AND REJECTIONS
The objection to the specification is withdrawn in view of Applicant's amendments thereto.
All prior grounds of objection and rejection to claims 24 and 29-30 are rendered moot by the cancelation of the claims.
The prior grounds of rejection of claims 23 and 25-28 are withdrawn in view of Applicant's claim amendments.
The rejection of claims 22-23 under 35 U.S.C. § 102 as being anticipated by Bradner (WO 2019/079569 A1; cited in IDS) is withdrawn in view of Applicant's amendments incorporating the subject matter of claims 24 and 29.
Note on Claim Interpretation
As presently amended, the method of claim 22 comprises a “contacting” step, and claims 22 and 25 recite “administering” steps. The specification defines “administering” as “the placement of a compound as disclosed herein into a subject by a method or route which results in at least partial delivery of the agent at a desired site. (…) In some embodiments of any of the aspects, administration comprises physical human activity, e.g., an injection, act of ingestion, an act of application, and/or manipulation of a delivery device or machine” (¶ 00216). The specification defines “contacting” as “any suitable means for delivering, or exposing, an agent to at least one cell. Exemplary delivery methods include, but are not limited to, direct delivery to cell culture medium, perfusion, injection, or other delivery method well known to one skilled in the art. In some embodiments of any of the aspects, contacting comprises physical human activity, e.g., an injection; an act of dispensing, mixing, and/or decanting; and/or manipulation of a delivery device or machine” (¶ 00217).
The Examiner is treating the terms “administering” and “contacting” as synonymous given the overlap in their meanings (i.e., partial or complete delivery of an agent) as recited in Applicant's disclosure.
NEW OBJECTIONS AND REJECTIONS NECESSITATED BY CLAIM AMENDMENT
Warning: Claim Objections
Applicant is advised that should claims 34-35 be found allowable, claims 36-37, respectively, will be objected to under 37 CFR 1.75 as being substantial duplicates thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 112(b)
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 25 and 46 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.
Claim 25 recites the method of claim 22, further comprising the step of administering a polypeptide comprising (i) at least one of a small molecule acceptor peptide and a small molecule, and (ii) at least one of a binding domain specific for a target, an antibody, and an antibody reagent. Claim 22 previously recites contacting the synthetic signaling system or small molecule-controlled signaling peptide with (a) at least one of a surface-attached polypeptide comprising a small molecule acceptor peptide and a surface-attached polypeptide comprising the small molecule, and (b) at least one of a soluble molecule comprising a small molecule acceptor peptide and a soluble molecule comprising the small molecule. The claim is indefinite because it is not sufficiently clear in claim 25 whether the polypeptide administered in the further administration step is intended to refer to the small molecule acceptor peptide/small molecule peptides that are contacted in the previous step or if they refer to separate entities.
It is generally noted that by virtue of the contacting step, it would logically follow that both of the contacting agents have to be administered to the subject in order to be in contact with one another.
Claim 46 recites the method of claim 24, which is now canceled. Accordingly, the metes and bounds of the claim cannot be determined and the claim is indefinite.
Claim Rejections - 35 USC § 102
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.
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.
Claims 22-23, 25-28, and 31-39 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Young (US 2018/0118808 A1; cited in IDS). This is a maintained rejection that has been updated to reflect Applicant's claim amendments.
Young discloses switchable chimeric receptors and use thereof in methods of treatment (e.g., Abstract). Young teaches that introduction of a switch allows for the control of CAR-T cell activity and associated immune responses, including mitigating cytokine storm (e.g., ¶ 0003-0004). Pertinent to the instantly claimed invention, Young discloses methods of treating a disease or condition (e.g., cancer) in a subject in need thereof that comprise administering a chimeric receptor-effector cell switch of the invention (e.g., ¶ 0015-0016). The switchable chimeric receptor systems of the invention comprise (1) a chimeric receptor comprising (a) a non-antibody extracellular domain that interacts with a chimeric receptor binding partner, (b) a transmembrane domain, and (c) an intracellular signaling domain (e.g., a CD3ζ stimulatory domain), and (2) a switch (or “polypeptide”) comprising the chimeric receptor binding partner (e.g., a small molecule, reading on “a soluble molecule comprising the small molecule”) and a targeting moiety (e.g., an antibody or an antibody fragment; reading on a surface-attached polypeptide comprising the small molecule”) (e.g., Figure 2; claims 1-19, 55-56; ¶ 0005-0010), pertinent to claims 22, 25, 32-33, and 38. Young further provides a chimeric receptor-effector cell switch comprising (a) a chimeric receptor binding partner that interacts with a non-antibody extracellular domain of a chimeric receptor on an effector cell, and (b) a targeting moiety that interacts with a cell surface molecule (e.g., HER2 or CD19, i.e., cancer cell surface-associated markers) on a target cell (e.g., claims 57-67, 92-94; ¶ 0011), further pertinent to claims 22 and 25-28. Upon binding of the antibody that interacts with a cell surface molecule, the chimeric receptor binding partner would become surface-attached. Relevant to claims 23 and 31, the switchable chimeric receptor-effector cells of the invention are generally T cells (e.g., Abstract; ¶ 0010).
Regarding claims 34-37, Young teaches that the chimeric receptors may comprise at least a portion of a cytoplasmic signaling domain comprising CD28 (e.g., ¶ 0051-0052).
Regarding claims 38-39, Young teaches that the small molecule bound by the chimeric receptor binding partner is selected from biotin among others (e.g., ¶ 0104-0105, 0123).
Response to Arguments
Applicant's arguments filed April 8, 2026 have been fully considered but they are not considered persuasive.
Applicant submits that the cited reference of Young “could not teach contacting with both a surface-attached polypeptide and a soluble molecule, as the chimeric receptor binding partner of Young would be one or the other in the presence of the synthetic signaling system or small molecule-controlled signaling peptide”. Remarks at pages 7-8. Applicant further submits that the recited method “exerts control over the ‘small molecule-controlled signaling peptide’ not disclosed in Young”, citing a passage in ¶ 0095 of the instant specification related to a method of controlling signaling or activity of a first cell comprising a cell surface receptor polypeptide comprising an extracellular domain that binds specifically to a small molecule. Remarks at page 8.
In response, it is held that Young still anticipates the broadest reasonable interpretation of the claims as presently amended. Young teaches (1) effector cells comprising a switchable chimeric receptor, comprising an antigen-binding domain that binds to a small molecule, a transmembrane domain, and an intracellular CAR stimulatory domain, reading on a “cell comprising a small molecule-controlled signaling polypeptide” as recited in claim 22, and (2) chimeric receptor-effector cell switches that interacts with a target cell, comprising (a) a chimeric receptor binding partner (e.g., small molecule) and a targeting moiety (e.g., an antibody), reading on “a polypeptide comprising at least one of … a small molecule; and at least one of … an antibody” as recited in claim 25, which further reads on the “at least one of … a surface-attached polypeptide comprising the small molecule; and at least one of …a soluble molecule comprising the molecule” as recited in claim 22, which are present in a single entity comprising both of the claimed elements and come into contact with the small molecule-controlled signaling polypeptide as required by the claimed method. The teachings of Young are believed Applicant's cited passage of ¶ 0095 in the instant specification, which is drawn to a (separate?) method of controlling signaling or activity of a cell comprising a system reading on the small molecule-controlled signaling polypeptide, based on the highlighted interpretation below, where:
The chimeric receptor-effector cell reads on “a first cell…” as set forth below;
The “surface-attached molecule” comprises the targeting moiety of the switch of Young, which interacts a cancer cell (as required in instant claims 25-28); and
“small molecule” comprises the small molecule (e.g., soluble small molecule) which is bound by the chimeric receptor expressed on the effector cell.
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Applicant appears to argue that the claimed synthetic signaling system or small molecule-controlled signaling peptide is contacting both of “the surface-attached polypeptide…” and the “soluble molecule” simultaneously as contrasted with Young. However, claim 22 expressly recites that the synthetic signaling system or small molecule-controlled signaling peptide comprises “a domain that binds specifically to a small molecule”. How can said synthetic signaling system simultaneously be considered as contacting the “surface-attached polypeptide” unless the surface-attached polypeptide and the small molecule (which is what is bound by the synthetic signaling system) are structurally linked (such as is implied by the recitation of “a surface-attached polypeptide comprising the small molecule” in the claim)?
For at least these reasons, the rejection is maintained.
Claim Rejections - 35 USC § 103
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.
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.
(1)
Claims 22-23, 25-28, 31-39, and 47 are rejected under 35 U.S.C. 103 as obvious over Lohmueller (Oncoimmunology (2018) 7(1): e1368604). This is a maintained rejection that has been updated to reflect Applicant's amendments to the claims.
Lohmueller teaches that the creation of CARs that bind to common tag molecules (e.g., FITC or biotin, conjugated to TAA-specific antibodies) seeks to address known challenges with the application of CAR therapy, namely, antigen loss by tumors and tumor heterogeneity (e.g., Introduction). Lohmueller describes anti-tag CARs (“AT-CARs”) that bind to tags on tumor-targeting antibodies (e.g., Abstract). Lohmueller discloses, “So-called anti-tag CAR (AT-CAR) therapy would be designed so that patients are infused with a tagged, TAA-specific antibody that binds to tumor cells, followed by T cells expressing AT-CARs that react with the tagged antibodies on tumor cells (Fig. 1A). This approach has the potential to allow for sequential or simultaneous targeting of multiple tumor antigens with different antibodies. Additionally, the activity of AT-CARs can be regulated by altering the concentration of tagged antibodies or halting antibody administration for better control over potential toxicities” (Introduction, page 1).
Lohmueller generated CAR-T cells expressing an affinity-enhanced monomeric streptavidin (mAS2) protein engineered to have high affinity for biotin (i.e., a domain that binds to a small molecule), a CD28 transmembrane/cytoplasmic domain, and a CD3ζ stimulatory domain (which, as evidenced by the instant specification at page 25, is an exemplary “CAR stimulatory domain”) (e.g., pages 1-2; Figure 1), relevant to the instantly claimed small molecule-controlled signaling peptide, which was co-administered with a biotinylated anti-CD20 antibody (rituximab) or a biotinylated anti-CD19 antibody (FMC63) in vitro to activate the CAR-T cells, inducing cytokine release and tumor lysis (e.g., pages 2-4; Figures 3-4), relevant to claims 22-23, 25-28, 31-39, and 47.
In contrast to the instant claims, Lohmueller does not expressly teach performing an in vivo method that comprises administering the mSA2 CAR-T cells, alone or in combination with a biotinylated anti-TAA antibody. However, Lohmueller does disclose that future experiments will include in vivo testing of mSA2 CAR-T cells with differing biotinylated antibody doses and schedules in mice bearing human tumor xenografts, thereby reading on a treatment method that comprises administering cells comprising a small molecule-controlled signaling peptide (mSA2 CAR, pertinent to claims 22-23) and a polypeptide comprising a small molecule (biotin) conjugated to an antibody against a cancer cell-specific antigen (CD19 or CD20) to a subject in need of an immunotherapy, wherein said antibody would be a surface-attached polypeptide upon binding to the surface of a cancer cell expressing the target antigen (pertinent to claims 24-29).
Accordingly, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to administer a cell comprising a small molecule-controlled signaling polypeptide (i.e., the mSA2 CAR-T cell) in combination with a surface-attaching polypeptide comprising a tumor-targeting antibody (i.e., “at least one of … an antibody”, which “binds specifically to a marker on the surface of a diseased cell”, wherein “the diseased cell is a cancer cell”) that is biotinylated (i.e., comprises a small molecule) in a method of treatment for a subject in need of immunotherapy. The skilled artisan would have been motivated to do so because Lohmueller teaches that the mSA2 CAR T cells possess anti-tumor activity and are specifically activated only when the biotinylated antibody was bound to the surface of a target cell (e.g., a cancer cell) expressing the target antigen (see pages 2-3). Furthermore, Lohmueller teaches that the system can be used to potentially target many different tumor types and can be regulated by adjusting the concentration of biotinylated antibody to reduce potential toxicity (e.g., page 1). There would have been a reasonable expectation of success because it was within the skill of one of ordinary skill in the art at the time of filing to generate and to administer antibodies (with or without a synthetic tag) having specificity for a tumor-associated antigen as well as CAR constructs having specificity for a variety of antigens, including synthetic antigens such as a common tag (e.g., FITC or biotin).
Response to Arguments
Applicant's arguments filed April 8, 2026 have been fully considered but they are not considered persuasive.
Applicant submits that the cited reference of Lohmueller “could not teach contacting with both a surface-attached polypeptide and a soluble molecule, as the polypeptide of Young [sic] would be one or the other in the presence of the synthetic signaling system or small molecule-controlled signaling peptide”. Remarks at page 9. Applicant further submits that the recited method “exerts control over the ‘small molecule-controlled signaling peptide’ not disclosed in Lohmueller, citing a passage in ¶ 0095 of the instant specification related to a method of controlling signaling or activity of a first cell comprising a cell surface receptor polypeptide comprising an extracellular domain that binds specifically to a small molecule. Remarks at page 9.
In response, it is held that Lohmueller still renders obvious the instantly claimed invention when considering the broadest reasonable interpretation of the claims. Specifically, Lohmueller teaches (1) T cells expressing a CAR comprising a domain that specifically binds to a small molecule (i.e., an affinity-enhanced mSA2 protein engineered to bind to biotin), a transmembrane domain, and an intracellular signaling domain, reading on a cell comprising a small molecule-controlled signaling polypeptide, and (2) a polypeptide comprising a biotinylated antibody that binds to a cell-surface molecule such as CD19 or CD20 (i.e., a surface-attached polypeptide comprising the soluble small molecule biotin), and conceives of the administration thereof in a subject in need of an immunotherapy. These elements can be similarly applied to the cited portion of Applicant's disclosure (¶ 0095).
Accordingly, the rejection is maintained.
(2)
Claims 22 and 40-43 are rejected under 35 U.S.C. 103 as obvious over Lohmueller (Oncoimmunology (2018) 7(1): e1368604) as applied to claims 22-23, 25-28, 31-39, and 47 above, further in view of Irvine (US 2020/0230221 A1; published July 23, 2020; earliest priority date: September 19, 2017) and Brinkmann (U.S. Patent No. 9,765,153). This is a new rejection necessitated by claim amendment.
The teachings of Lohmueller are recited in the 35 U.S.C. § 103 rejection above.
However, Lohmueller does not expressly teach that the binding domain that binds specifically to biotin is an antibody or antibody reagent comprising light chain and heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 4-9, respectively.
Irvine teaches amphiphilic ligand conjugates comprising a CAR ligand (e.g., a tag such as biotin), which activate and induce proliferation of T cells expressing a CAR comprising an antigen-binding domain against said tag (i.e., AT-CAR) and increase their anti-tumor activity (e.g., Abstract; ¶ 0004-0012, 0149-0178). Irvine teaches that the CARs of the invention comprise an antigen-binding domain that is selected from scFv, scFab, and others, containing three heavy chain CDRs and three light chain CDRs (e.g., ¶ 0190-0196), relevant to claims 40-42.
Brinkmann discloses anti-biotin antibodies. Brinkmann discloses an exemplary murine anti-biotin antibody comprising a light chain variable region (VL) of SEQ ID NO: 8, which comprises three CDRs comprising the amino acid sequences of SEQ ID NOs: 5-7, respectively (which share 100% sequence identity to instant SEQ ID NOs: 4-6, respectively), and a heavy chain variable region (VH) of SEQ ID NO: 4 comprising three CDRs comprising the amino acid sequences of SEQ ID NOs: 1-3, respectively (which share 100% sequence identity to instant SEQ ID NOs: 7-9, respectively) (e.g., col 10-14, 30-31, 43-48), relevant to claim 43.
Based on the further teachings of Irvine and Brinkmann, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to modify the anti-tag CAR taught by Lohmueller by substituting as the antigen-binding domain an scFv or scFab-based antigen-binding domain comprising a combination of the heavy chain and light chain CDRs such as that set forth by Brinkmann, for use in treating a subject in need of immunotherapy. The skilled artisan would have been motivated to do so because antibody-based antigen-binding domains likewise display high affinity for their respective antigen, and one of ordinary skill in the art would recognize the antibodies of Brinkmann as being suitable for the desired purpose of specifically binding to biotin. There would have been a reasonable expectation of success because it is routine and conventional in the art to use antibody-based reagents (e.g., scFv or scFab) as an antigen-binding domain in CAR constructs.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
(1)
Claims 22-23, 25-28, 31-39 and 47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 11,672,828 in view of Young (US 2018/0118808 A1; supra) or, in the alternative, Lohmueller (Oncoimmunology (2018) 7(1): e1368604; supra). This is a maintained rejection that has been updated to reflect Applicant's claim amendments.
The reference patent claims a combination comprising (I) a cell or set of cells comprising one or more nucleic acids encoding a small molecule-controlled polypeptide comprising at least a first signaling domain and a polypeptide comprising a domain that binds specifically to a small molecule, and (II) a surface-attached molecule comprising a binding domain specific for a target, and a small molecule acceptor peptide (e.g., patented claims 15-18), relevant to claims 22, 25, and 32. Patented claims 16-18 further recite that the domain that specifically binds to a small molecule binds to biotin, is extracellular, relevant to claims 38-39.
The reference patent also claims a synthetic signaling system comprising (1) a small molecule-controlled signaling polypeptide comprising a small molecule acceptor peptide, a transmembrane domain, and a CAR stimulatory domain; (2) a polypeptide comprising a domain that binds specifically to the small molecule (e.g., biotin); and (3) a surface-attached molecule comprising a binding domain specific for a target and a small molecule acceptor peptide; and further comprising a soluble molecule comprising a small molecule (e.g., patented claims 1-14), further relevant to claims 22 and 25. Patented claims 21-23 recite a method of treating a subject in need of immunotherapy by administering an immune cell (T cell) comprising a synthetic signaling system, said system comprising (1) a small molecule-controlled signaling polypeptide comprising a small molecule acceptor peptide and at least a first signaling domain and (2) a polypeptide comprising a domain that binds specifically to a small molecule, pertinent to claims 22-23 and 31.
However, the reference patent does not teach a small molecule-controlled polypeptide comprising all three of a small molecule-binding domain, a transmembrane domain, and a CAR stimulatory domain, which is administered in a treatment method for a subject in need of immunotherapy, nor that a co-administered surface-attached molecule comprises an antibody specific for a cancer cell surface antigen.
The teachings of Young and Lohmueller, with respect to regulatable (switchable) CAR-T cell systems that may be used in methods of treating a subject in need of an immunotherapy, are discussed in the rejections under 35 U.S.C. § 102 and 103 above.
It would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to modify the synthetic signaling system described in the reference patent to arrive at a cell comprising a small molecule-controlled signaling peptide comprising a polypeptide having a domain that binds to a small molecule (e.g., biotin), a transmembrane domain, and an intracellular signaling domain, wherein said small molecule-controlled signaling peptide is co-administered with a surface-attaching molecule comprising a tumor-targeting antibody and the small molecule to which the signaling peptide binds, and use of such a construct in a method of treatment. The skilled artisan would have been motivated to do so because, as demonstrated by both Young and Lohmueller, such a system would allow for administration of a disease-treating therapeutic cell (e.g., a CAR-T cell) whose activity could be modulated in vivo to minimize toxic effects. There would have been a reasonable expectation of success because it was within the skill of one of ordinary skill in the art at the time of filing to generate and to administer antibodies (alone or conjugated to a small molecule) having specificity for a tumor-associated antigen as well as CAR constructs having specificity for a variety of antigens, including small molecule-based synthetic tags (e.g., biotin).
Response to Arguments
Applicant's arguments filed April 8, 2026 have been fully considered but they are not considered persuasive.
Applicant submits that “Young and Lohmueller do not teach or suggest the presently claimed methods for at least the foregoing reasons and that the claims are not obvious over the cited combinations of art”. Remarks at pages 9-10.
In response, it is noted that comments regarding the applicability of Young and Lohmueller to the instantly claimed invention are summarized in the Responses above.
The rejection is maintained.
(2)
Claims 22 and 40-43 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 11,672,828 in view of Lohmueller (Oncoimmunology (2018) 7(1): e1368604; supra) as applied to claims 22-23, 25-28, 31-39, and 47 above, further in view of Irvine (US 2020/0230221 A1; supra) and Brinkmann (U.S. Patent No. 9,765,153; supra). This is a new rejection necessitated by claim amendment.
The teachings of the reference patent are recited in the non-statutory double patenting rejection above.
However, the reference patent does not expressly claim that the binding domain that binds specifically to biotin is an antibody or antibody reagent comprising light chain and heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 4-9, respectively.
The teachings of Lohmueller, Irvine, and Brinkmann are recited in the 35 U.S.C. § 103 rejections above.
In view of the above, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to modify an anti-biotin CAR such as that collectively taught by the reference patent and Lohmueller by substituting as the antigen-binding domain an scFv or scFab-based antigen-binding domain comprising a combination of the heavy chain and light chain CDRs such as that set forth by Brinkmann. The skilled artisan would have been motivated to do so because antibody-based antigen-binding domains likewise display high affinity for their respective antigen, and one of ordinary skill in the art would recognize the antibodies of Brinkmann as being suitable for the desired purpose of specifically binding to biotin. There would have been a reasonable expectation of success because it is routine and conventional in the art to use antibody-based reagents (e.g., scFv or scFab) as an antigen-binding domain in CAR constructs.
Allowable Subject Matter
Claims 44-45 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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.
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/ELIZABETH A SHUPE/Examiner, Art Unit 1643
/Brad Duffy/Primary Examiner, Art Unit 1643
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