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 .
Status of the Claims
Applicant’s submissions filed 06 February 2026 has been entered. Claims 51, 54-55, 59, and 79-87 are pending. Claims 51 and 59 have been amended, while claims 1, 3-6, 8, 10-13, 28, 30-31, 35, 37, and 53 have been cancelled without prejudice or disclaimer and claims 79-87 have been newly added. Therefore, prosecution on the merits continues for claims 51, 54-55, 59, and 79-87.
Status of Prior Rejections/Response to Arguments
RE: Nucleotide/amino acid sequence disclosure
The addition of an Incorporation by Reference paragraph and sequence identifiers to the primer sequences within Page 82 of the substitute Specification filed 06 February 2026 obviates the objections of record.
Therefore, the objections are withdrawn.
RE: Objection to the Specification
The substitute Specification filed 06 February 2026 is acknowledged and entered into the application filed. With that, Applicant has removed reference to colored drawings within Pages 14-16.
However, the substitute Specification has not removed the browser-executable code limited to the top-level domain name within Page 84. For reference, the top-level domain name of the instant browser-executable code is “n2t.net”.
Therefore, the objection regarding the reference to colored drawings is withdrawn but the objected regarding browser-executable code is maintained.
RE: Objection to claims 5, 11, and 51
The cancellation of claims 5 and 11 renders the objections moot for those claims. For the remaining claim, Applicant’s amendments to instant claim 51 obviate the objection of record.
Therefore, the objection is withdrawn.
RE: Rejection of claim 12 under 35 USC 112(b)
The cancellation of claim 12 renders the rejection moot. Therefore, the rejection is withdrawn.
RE: Rejection of claims 1, 3-6, 8, 10-13, 28, 30-31, 35, 37, 51, 53-55, and 59 under 35 USC 103 over Powell et al
The cancellation of claims 1, 3-6, 8, 10-13, 28, 30-31, 35, 37, and 53 renders the rejection moot for those claims. For the remaining claims, Applicant’s arguments filed 06 February 2026 have been fully considered but they are not persuasive.
Applicant has traversed the rejection, asserting in Pages 8-10 of the Remarks filed 06 February 2026 that SpyCatcher T cells comprising a 4-1BB intracellular domain unexpectedly exhibit a greater specificity for high target antigen-expressing cells and display a more titratable response to the administered targeting agent when compared to equivalent CD28 intracellular domain-containing constructs. Applicant cites Pages 38, 70, 91, 93 and Figures 3F, 8A-B of the instant disclosure to support these assertions. In response, the Examiner respectfully submits that the “unexpected results” are not commensurate in scope with the instant claims, as the cited sections within the instant disclosure require the cell to be a T cell, the extracellular domain to be a SpyCatcher extracellular domain, and the agent linked to a reciprocal adaptor molecule to be a SpyTag-DARPin. It is also of note that the 4-1BB-containing cells comprise a CD8α hinge and CD8α transmembrane domain, while the CD28-containing cells comprise a CD8α hinge and CD28 transmembrane domain. See Page 90 and Figure 2A of the instant disclosure.
Furthermore, the Examiner respectfully reminds Applicant that when submitting evidence asserted to establish unobvious results, there is a burden on Applicant to indicate how the examples asserted to represent the claimed invention are considered to relate to the examples intended to represent the prior art and, particularly, to indicate how those latter examples do represent the closest prior art. The evidence relied upon should also be reasonably commensurate in scope with the subject matter claimed and illustrate the claimed subject matter relative to the prior art subject matter. See MPEP § 2145. It should also be established that the differences in the results are in fact unexpected and unobvious and of both statistical and practical significance. See MPEP § 716.02(b). In the instant case, Applicant has failed to indicate how the alleged unexpected results differ from the closest prior art.
Therefore, the rejection is maintained and amended to encompass the claims as currently written.
RE: Rejection of claims 1, 3-6, 8, 10-13, 28, 30-31, 35, 37, 51, 53-55, and 59 under 35 USC 103 over claims 2-4, 9-16, and 19 of US 11,377,481 B2 in view of Powell et al
The cancellation of claims 1, 3-6, 8, 10-13, 28, 30-31, 35, 37, and 53 renders the rejection moot for those claims. For the remaining claims, Applicant’s arguments filed 06 February 2026 have been fully considered but they are not persuasive.
Applicant has traversed the rejection, asserting in Page 10 of the Remarks filed 06 February 2026 that the amendments to independent claim 51, “wherein the antigen is expressed by the tumor and a healthy cell in the mammal, wherein expression of the antigen by the tumor is greater than expression of the antigen by the healthy cell, and wherein the effective amount of the agent is an amount sufficient for the cell genetically modified to express the immune receptor to induce the immune response to the tumor, but not to the healthy cell”, are not taught by Powell et al. In response, the Examiner respectfully submits that Powell et al disclose agents that are specific for tumor-associated antigens that are pre-determined to have increased expression by a tumor when compared to expression in a healthy cell (Pages 16, 58-59, 63-64). Powell et al further disclose that the agents are screened to determine the time of maximal binding to the antigen in target tissue without having any residual agent in the healthy tissue (Pages 10, 59). Accordingly, Powell et al teach the limitations of the instant claim such that the ordinary artisan would have been reasonably able to perform the method as claimed.
Therefore, the rejection is maintained and amended to encompass the claims as currently written.
Maintained Grounds of Rejection
Claim Interpretation
Applicant recites in Page 26 of the instant Specification that the terms "SpyTag" and "SpyCatcher" refer to a convenient protein coupling tool that overcomes the generally weak protein-protein interaction (with "Spy" referring to the bacterium Streptococcus pyogenes). Applicant notes that SpyTag is a genetically encoded peptide that forms a spontaneous amide bond upon binding its genetically encoded partner SpyCatcher.
Applicant defines "universal immune receptor" in Page 28 of the instant Specification as a receptor having two split but interactive parts, (i) one or more intracellular T cell signaling domains attached to an extracellular adaptor molecule and (ii) a targeting ligand that is able to bind the adaptor molecule via a reciprocal adaptor molecule and also able to specifically bind a target (e.g., an antigen on a target cell, such as an antigen expressed by a tumor cell).
Applicant also recites in Page 28 of the instant Specification that an "adaptor molecule" and a "reciprocal adaptor molecule" (or "tag" and "reciprocal tag") refer to a pair of components in a binding pair system, where each component specifically binds to the other. Applicant elaborates that the "adaptor molecule" refers to one of the pair, and the "reciprocal adaptor molecule" refers to the binding partner of the adaptor molecule.
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.
Claims 51, 54-55, 59, and 79-87 remain rejected under 35 U.S.C. 103 as being unpatentable over Powell et al (WO 2017/112784 A1, of record on the IDS filed 18 September 2024).
Powell et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2), with a publication date of 29 June 2017.
Regarding claims 51, 54-55, 59, 79, 83, and 86: Powell et al disclose methods for adoptive T cell therapy in treating cancer, wherein a T cell genetically modified to express a universal immune receptor that comprises a SpyCatcher extracellular domain bound to an extracellular hinge region, a transmembrane domain, and a TCR intracellular signaling domain comprising a 4-1BB costimulatory intracellular domain is administered into a mammal suffering from cancer (Abstract; Pages 2-6, 21-22, 27-28, 39, 50-52, 56, 62-64).
Powell et al further disclose that agents linked to SpyTag – the reciprocal adaptor molecule to SpyCatcher – are also administered to the mammal, wherein the agents are antigen-specific antibodies (Pages 22, 29-30, 51-52). Powell et al further disclose that the agents may be specific for antigens expressed by tumors, and that the agents can be specific for a plurality of different tumor-associated antigens (Pages 25-26, 52-54).
Powell et al further disclose that the agents are specific for tumor-associated antigens that are pre-determined to have increased expression by a tumor when compared to expression in a healthy cell (Pages 16, 58-59, 63-64). Powell et al further disclose that the agents are screened to determine the time of maximal binding to the antigen in a target tissue – or tumor – without having any residual agent in the healthy tissue (Pages 10, 59).
However, Powell et al do not exemplify or reduce to practice a method of stimulating a universal immune receptor-mediated immune response to a tumor in a mammal, wherein a cell genetically modified to express an immune receptor comprising a T cell receptor intracellular signaling domain, an intracellular domain of 4-1BB, a transmembrane domain, and an extracellular domain comprising an adaptor molecule is administered to the mammal, as well as a first agent and second agent each linked to a reciprocal adaptor molecule, wherein the first agent and second agent each specifically bind a first antigen and a second antigen that are overexpressed by the tumor when compared to expression in a healthy tissue, and the first antigen and the second antigen are different antigens, as required by instant claims 51 and 86.
Therefore, it would have been prima facie obvious to have modified the methods of Powell et al such that the genetically modified cell and agents are administered to the mammal. One of ordinary skill in the art before the effective filing date of the invention would have recognized that the cells and agents can be administered in vivo, as Powell et al disclose corresponding treatments to in vitro tumor models, and thereby would have had a reasonable expectation of success in adapting the protocols from in vitro to in vivo (Pages 59-65). See MPEP § 2143(I)(G).
Consequently, Powell et al render obvious a method of stimulating a universal immune receptor-mediated immune response to a tumor in a mammal, wherein a T cell (claims 59, 83) genetically modified to express an immune receptor that comprises a SpyCatcher extracellular domain (claim 54) bound to an extracellular hinge region, a transmembrane domain, and a TCR intracellular signaling domain comprising a 4-1BB costimulatory domain is administered to the mammal, as well as antigen-specific antibodies that are each linked to SpyTag (claims 55, 79), wherein the antigen-specific antibodies bind a plurality of different antigens that are overexpressed by the tumor when compared to expression in a healthy tissue (claim 86) and cause the genetically modified T cell to induce an immune response to the tumor but not to the healthy tissue. This therefore renders obvious the method of instant claim 51.
Regarding claims 80-81: Following the discussion of claim 51, Powell et al further disclose that antigen-specific antibodies that are each linked to SpyTag can be scFvs (Pages 3-6, 10, 21, 29). This therefore reads on the method of the instant claims.
Regarding claim 82: Following the discussion of claim 51, Powell et al further disclose that the T cell genetically modified to express an immune receptor is an autologous T cell (Pages 7, 12, 55). This therefore reads on the method of the instant claim.
Regarding claims 84-85: Following the discussion of claim 51, Powell et al further disclose that the genetically modified T cells can be administered to the mammal before the antigen-specific antibodies (claim 85), or that the antigen specific-antibodies can be contacted with the genetically modified T cells prior to administration (claim 84) such that the genetically modified T cells and antigen-specific antibodies are administered to the mammal pre-bound via the SpyCatcher/SpyTag covalent pairing (Page 51). This therefore reads on the methods of the instant claims.
Regarding claim 87: Following the discussion of claim 51, Powell et al further disclose that the mammal is a human (Pages 16-17, 33, 55). This therefore reads on the method of the instant claim.
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.
Claims 51, 54-55, 59, and 79-87 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-4, 9-17, and 19-20 of U.S. Patent No. 11,377,481 B2 in view of Powell et al (WO 2017/112784 A1, of record on the IDS filed 18 September 2024).
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims render obvious the instant claims. More specifically, the patented claims are not identical because no single patented claim discloses all of the limitations of any of the instant claims; however, each of the limitations of the instant claims are disclosed by separate patented claims, or rendered obvious by the accompanying prior art. The fact that each of the elements were claimed in the patent, just not in a single claim, still renders obvious the instant invention because each of the features, though separately claimed, can be physically combined into a single embodiment.
Patent claim 2 is directed to a universal immune receptor fusion protein comprising, in order, a SpyCatcher extracellular binding domain, a CD8α extracellular hinge region, a CD8α transmembrane domain, a 4-1BB costimulatory molecule and a CD3-zeta intracellular signaling domain.
Patent claims 3-4 are directed to an immune cell comprising a nucleic acid molecule encoding the universal immune receptor fusion protein of claim 2.
Patent claim 9 is directed to a method for stimulating a universal immune receptor-mediated immune response in a mammal, the method comprising administering to a mammal an effective amount of the cells of claim 4.
Patent claim 10 further limits the method of patent claim 9, wherein the universal immune receptor-mediated immune response is stimulated when the isolated universal immune receptor fusion protein forms a covalent bond with a fusion protein comprising SpyTag and a targeting ligand.
Patent claims 14-16 further limit the method of patent claim 9, wherein the method either comprises administering the fusion protein comprising SpyTag to the mammal prior to administering the cells, or binding the universal immune receptor fusion protein with the fusion protein comprising SpyTag prior to administering the cells to the mammal.
Patent claim 19 further limits the method of patent claim 9, wherein the mammal is treated for cancer.
The combination of patent claims 2-4, 9-10, 14-16, and 19 fail to teach that the fusion protein comprising SpyTag specifically binds antigens that are overexpressed in tumors when compared to healthy tissue, and that the effective amount of the agent is an amount sufficient for the cell genetically modified to express the immune receptor to induce the immune response to the tumor, but not to the healthy tissue.
Powell et al, however, teach a method of stimulating a universal immune receptor-mediated immune response to a tumor in a mammal, wherein an immune cell genetically modified to express an immune receptor that comprises a SpyCatcher extracellular domain bound to an extracellular hinge region, a transmembrane domain, and a TCR intracellular signaling domain comprising a 4-1BB costimulatory domain is administered to the mammal, as well as antigen-specific antibodies that are each linked to SpyTag, wherein the antigen-specific antibodies bind a plurality of different antigens that are overexpressed by the tumor (Abstract; Pages 2-6, 16, 21-22, 25-30, 39, 50-54, 56, 58-59, 62-64).
Powell et al further disclose that the agents are specific for tumor-associated antigens that are pre-determined to have increased expression by a tumor when compared to expression in a healthy cell (Pages 16, 58-59, 63-64). Powell et al further disclose that the agents are screened to determine the time of maximal binding to the antigen in a target tissue – or tumor – without having any residual agent in the healthy tissue (Pages 10, 59).
Therefore, it would have been prima facie obvious to have modified the claims of the patent such that the fusion protein comprising SpyTag specifically binds tumor antigen(s) that are pre-determined to be overexpressed by tumors within the mammal, and allow for the induction of an immune response to the tumor but not healthy tissue. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to generate fusion proteins that specifically target the tumor antigens, and would have had a reasonable expectation of success based on the disclosure of Powell et al.
Consequently, patent claims 2-4, 9-10, 14-16, and 19 as modified by Powell et al render obvious instant claims 51, 54-55, 79, and 84-86.
With that, instant claims 59, 80-83, and 87 are known from the patent claims and can be further incorporated into the methods rendered obvious by patent claims 2-4, 9-10, 14-16, and 19 as modified by Powell et al:
Patent claims 11-13, 17, and 20 teach the limitation recited in instants claim 59, 80-83, and 87.
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 ALYSSA G WESTON whose telephone number is (571)272-0337. The examiner can normally be reached Monday-Thursday 8AM - 4PM (CT); Friday 8AM - 11AM (CT).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALYSSA G WESTON/Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
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