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
Claims 1 and 47 – 66 were pending. Claims 1, 47 – 61, and 64 – 66 have been amended. Claims 1 and 47 – 66 are currently pending and are the subject of this Office Action.
Specification
Previous objection, withdrawn: the disclosure is objected to because of informalities.
In view of the amendments to the specification in the reply of 09/02/2025, this objection is withdrawn.
Claim Objections
Previous objection, withdrawn: claim 47 is objected to because of informalities.
In view of the amendments to claim 47 in the reply of 09/02/2025, this objection is withdrawn.
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.
Previous rejection, withdrawn: claims 47 – 61 and 64 – 65 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly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.
In view of the claim amendments in the reply of 09/02/2025, this rejection is withdrawn.
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.
Previous rejection, maintained: claims 1, 48 – 49, 52, and 60 – 66 are rejected under 35 U.S.C. 103 as being unpatentable over ADDIS (WO 2018/234319 A1, published 12/27/2018, on IDS submitted 05/02/2025) in view of CONROY (WO 2020/157211 A1, published 08/06/2020, on IDS submitted 05/02/2025).
The present application is directed to multi-domain, single-chain binding molecule comprising: i) a peptide-major histocompatibility complex (pMHC) binding domain which binds to a SLLQHLIGL (SEQ ID NO: 1)-HLA-A*02 complex, the pMHC binding domain comprising a first variable region linked to a constant region (VC1) and a second variable region linked to a constant region (VC2), wherein VC1 and VC2 dimerize to form the pMHC binding domain, wherein VC1 comprises a TCRβ variable region comprising CDR1 having the sequence of SEQ ID NO: 9 (LNHDA), CDR2 having the sequence of SEQ ID NO: 10 (SQIMGDE), and CDR3 having the sequence of SEQ ID NO:11 (CASSWWTGGASPIRF) and VC2 comprises a TCRα variable region comprising CDR1 having the sequence of SEQ ID NO: 3 (TISGTDY), CDR2 having the sequence of SEQ ID NO: 4 (GLTSN), and CDR3 having the sequence of SEQ ID NO: 5 (CILILGHSRLGNYIATF); ii) a CD3 immune effector (TCE) domain comprising an antibody light chain variable region (TCE-VL) and an antibody heavy chain variable region (TCE-VH); and iii) a half-life extending domain comprising a first IgG Fc region (FC1) and a second IgG Fc region (FC2), wherein the FC1 region and theFC2 region dimerize to form an Fc domain, wherein the CD3 immune effector domain is linked to the N terminus of VC1, VC1 is linked via its C terminus to the N terminus of the FC1 region, the FC1 region is linked via its C terminus to the N terminus of VC2, and VC2 is linked via its C terminus to the N terminus of the FC2 region; and wherein the pMHC binding domain and the CD3 immune effector domain are capable of binding to a pMHC complex and a T cell respectively.
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It is understood that the overall structure of the multidomain, single-chain binding molecule of claim 1 is represented by FIGs. 1A and 1B of the Drawings:
ADDIS is directed to T cell receptors (TCRs) that bind the HLA-A*02 restricted peptide SLLQHLIGL (SEQ ID NO: 1) derived from the germline cancer antigen PRAME. See abstract. ADDIS discloses that these TCRs may be in single chain format. See claim 20 and p. 19, line 18. ADDIS discloses the CDRs of SEQ ID NOs: 9 – 11 and 3 – 5. ADDIS’ SEQ ID NO: 17 discloses the present SEQ ID NOs: 9 – 11 with 100% identity, and ADDIS’ SEQ ID NO: 7 discloses the present SEQ ID NOs: 3 -5 with 100% identity. See Appendix of record.
ADDIS teaches that the TCRs may be in a single chain format. See p. 19, lines 18-29.
ADDIS teaches that the TCRs of the invention may be fused to anti-CD3 antibodies. See p. 21, line 25 – p. 22, line 30.
Thus ADDIS discloses a multi-domain, single-chain binding molecule with a pMHC binding domain which binds to a SLLQHLIGL (SEQ ID NO: 1) HLA-A*02 complex with a VC1 having a TCRβ variable region with CDR1 of SEQ ID NO:9 (LNHDA), CDR2 of SEQ ID NO: 10 (SQIMGDE), and CDR3 of SEQ ID NO:11 (CASSWWTGGASPIRF) and a VC2 having TCRα variable region comprising CDR1 of SEQ ID NO: 3 (TISGTDY), CDR2 of SEQ ID NO: 4 (GLTSN), and CDR3 of SEQ ID NO: 5 (CILILGHSRLGNYIATF) and ii) a CD3 immune effector domain comprising an antibody light chain variable region (TCE-VL) and an antibody heavy chain variable region (TCE-VH).
However, ADDIS does not disclose the addition to the binding molecule of an FC1 and an FC2, wherein the FC1 region and FC2 region dimerize to form an Fc domain. Nonetheless, CONROY discloses this domain.
CONROY is directed to soluble multi-domain binding molecules comprising T cell receptors (TCR) having specificity for an antigen, an immunoglobulin Fc domain or an albumin-binding moiety; and an immune effector domain. See abstract. CONROY discloses a multi-domain binding molecule similar to that of present claim 1, with the exception that CONROY’s structure is composed of two single chains:
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CONROY’s Figure 1.
CONROY teaches that the preferred Fc domains are the Fc domains from IgG1 or IgG4. See p. 4-lines 5-7 and line 25.
Thus, the main difference between the overall structure of the present invention and CONROY’s is that the structure of present claim 1 consists of a linker between FC1 and the variable domain of the VC, which results in one single chain instead of CONROY’s two chains. However, it would have been obvious to one having ordinary skill in the art to add an additional linker in order to produce one single chain construct because of the advantages of single chain binding molecules, such as expression/production efficiency. Furthermore, there would have been a reasonable expectation of success of the single-chain binding molecule of claim 1, given that the domains have been known to be engineered (and connected via peptide linkers) into binding molecules that successfully treat disorders such as cancer as evidenced by the applied prior art.
Regarding claim 48, CONROY discloses that the CD3 effector domain comprises an antibody scFv. See claim 6.
Regarding claim 49, ADDIS discloses the TCR is an alpha-beta heterodimer, having an alpha chain TRAC constant domain sequence and a beta chain TRBC1 or TRBC2 constant domain sequence. (The constant, or C, regions of TCR alpha and beta chains are referred to as TRAC and TRBC respectively). See claim 17 and p. 3, lines 7 – 8.
Regarding claim 52, ADDIS discloses that an anti-CD3 antibody is covalently linked to the C- or N-terminus of the alpha or beta chain of the TCR optionally via a linker sequence and that the linker may be GGGGS. See claims 22 – 23.
Regarding claims 60 – 64, ADDIS discloses nucleic acid encoding the binding molecule (TCR), an expression vector, and host cell, which all may be utilized in a method to produce the binding molecule. See claims 27 – 29.
Regarding claim 65, ADDIS discloses the pharmaceutical composition comprising the binding molecule (TCR). See claims 31 – 32.
Regarding claim 66, ADDIS discloses a method of treating cancer expressing PRAME, comprising administering the pharmaceutical composition. See claims 33 and 34.
Additionally regrading claim 66 ADDIS discloses the peptide SLLQHLIGL (SEQ ID NO: 1) corresponds to amino acids 425-433 of the full length 40 PRAME protein and is presented on the cell surface in complex with HLA-A*02. This peptide-HLA complex provides a useful target for TCR-based immunotherapeutic intervention. See paragraph bridging pp. 1-2.
Response to Arguments
On page 13, third paragraph – p. 14, second paragraph, Applicant argues that “[t]he Office has failed to identify all claimed elements in the cited combination of references” and that “claim 1 requires that these individual domains be linked together to form a single-chain binding molecule in a specific orientation.”
Applicant’s arguments have been fully considered but not found persuasive because as discussed above, the structure of CONROY includes the binding domain, TCR variable domains, TCR constant domains, and the FC regions in a similar orientation as the structure of present claim 1. The main difference between the structure of CONROY and that of present claim 1 is the linking of the domains to form a single chain of present claim 1 instead of the two chains of CONROY’s structure. Furthermore, both ADDIS and CONROY teach that the engineered binding molecules may be in single chain format as discussed above, rendering such a format obvious. In addition, CONROY teaches the knob-into-hole (KiH) engineering, which facilitates proper dimerization and assembly of the binding molecule, and which also appears on the structure of present claim 1. The only difference between the structure of present claim 1 and that of CONROY is the linker between FC1 (Fc domain) and VC2 (TCRα domain) on the structure of present claim 1. However, CONROY teaches that “Fc may be fused to the other domains (i.e., the TCR or immune effector) via a linker” (see p. 4, line 11).
On page 15, last paragraph - p. 19, second paragraph of the reply, Applicant argues “the Office has not articulated a finding why the skilled artisan would have pursued the claimed binding molecule with a reasonable expectation of success”. In particular, Applicant argues that over 37 different molecular formats of single-chain and multi-chain molecular formats for activating T cells in vitro and that only the claimed structure, mol093, was able to activate both antigen-pulsed T2 cells and Mel624 cells (p. 17, last paragraph – p. 18 first paragraph of the reply).
Applicant’s arguments have been fully considered but not found persuasive because the testing of multidomain binding molecules rendered obvious by the cited references to arrive to the binding molecule with advantageous properties only requires optimization within prior art conditions or through routine experimentation. ADDIS and CONROY render the claimed multi-domain, single-chain binding molecule obvious for the reasons above and teach how to assay for T-cell activation (see Example 6, p. 30 of ADDIS and Example 1, part c, top of p. 18 of CONROY).
On page 18, last paragraph – p. 19, first paragraph, Applicant argues that the claimed binding molecule exhibits superior and unexpected properties that could not be predicted from the teachings of the cited combination of references and points to mol093 as having greater than 4-fold increase in T cell activation compared to the structure taught by CONROY (mol014).
Applicant’s arguments have been fully considered but not found persuasive because the figure on p. 18 of the reply shows Mol093 with an IFNγ release of about 1000 no. spots +/- SEM by antigen-pulsed T2 cells, and ADDIS’ binding molecule shows an IFNγ release of about 1000 no. spots +/- SEM by antigen-positive cells (within error; see Figure 7a at the end of the ADDIS document). Thus, ADDIS renders the T-cell activation of the claimed binding molecule obvious.
Furthermore, Applicant’s argument regarding FIG. 2 of the present specification is not found persuasive because the example is not commensurate in scope. Although CONROY renders the overall structure of the present binding molecule obvious, CONROY does not appear to have the same specific target or CDRs as the binding molecule of present claim 1 and thus may not function exactly in the same manner as the binding molecule of present claim 1. Nonetheless, as discussed above, ADDIS’ binding molecule does have the same target and same CDRs and activate T cells to similar levels as the claimed binding molecule, rendering the T-cell activation of the claimed binding molecule obvious.
Previous rejection, maintained: claim 47 is rejected under 35 U.S.C. 103 as being unpatentable over ADDIS in view of CONROY as applied to claims 1, 48 – 49, 52, and 60 – 66 above, and further in view of VOGELSTEIN (WO 2021/127184 A1, published 06/24/2021; see PTO-892: Notice of References Cited of 06/02/2025).
The teachings of ADDIS and CONROY are discussed above and are fully incorporated here.
VOGELSTEIN is directed to molecules including one or more antigen-binding domains (e.g., a single-chain variable fragment (scFv)) that can bind to a modified peptide (e.g., a tumor antigen) for assessing a mammal having or suspected of having cancer and/or for treating a mammal having cancer. See abstract. VOGELSTEIN discloses a molecule comprising an antigen-binding domain that can bind to a peptide-HLA complex (see claim 1) and the CDRs of present claim 47. VOGELSTEIN’s SEQ ID NO: 251 discloses present VL region’s CDR1, CDR2, and CDR3 of present claim 47 with 100% identity, and VOGELSTEIN’s SEQ ID NO: 305 discloses present VH region’s CDR1, CDR2, and CDR3 of present claim 47 with 100% identity. See Appendix of record.
Because ADDIS and CONROY renders a multi-domain, single chain binding molecule obvious as discussed above and VOGELSTEIN discloses an anti-CD3 scFV that was successful in treating cancer, it would have been obvious to modify ADDIS and CONROY’s binding molecule with VOGELSTEIN’s anti-CD3 CDRs to arrive to the invention of claim 47.
Response to Arguments
Page 19, fourth paragraph, of the reply of 09/02/2025 states that “Applicant submits that Vogelstein does not cure the deficiencies in the combination of Addis and Conroy described above. That is, Vogelstein does not teach or suggest the orientation of domains recited in claim 1. As such, all arguments advanced above with respect to claim 1 are equally applicable to claim 47.”
Applicant’s argument is not persuasive because ADDIS in view of CONROY renders the orientation of domains of the claimed binding molecule obvious as discussed above, and VOGELSTEIN teaches binding molecules having the anti-CD3 CDRs of present claim 47. Thus, because VOGELSTEIN’s binding molecule is effective at treating cancer, it would have been obvious to use VOGELSTEIN’s CDRs in ADDIS and CONROY’s multidomain binding molecule.
Previous rejection, maintained: claims 50 – 52 and 54 are rejected under 35 U.S.C. 103 as being unpatentable over ADDIS in view of CONROY as applied to claims 1, 48 – 49, 52, and 60 – 66 above, and further in view of POMA (WO 2022/020588 A1, published 01/27/2022; see PTO-892 of 06/02/2025).
The teachings of ADDIS and CONROY are discussed above and are fully incorporated here.
POMA is directed to methods for treating or preventing cancer comprising administering to a subject in need thereof an effective amount of a HER2 binding molecule. See abstract. POMA discloses that the six CDRs of the antigen binding domain are contributed by a VH and VL in an scFv format, the VH and VL are covalently attached, generally through the use of a linker as outlined herein, into a single polypeptide sequence, which can be either (starting from the N-terminus) VH-linker-VL or VL-linker- VH (See paragraph 0049), which renders present claim 50 obvious. POMA’s linker 1 differs from SEQ ID NO: 39 of present claim 51 by one G at the penultimate position of the linker. See Table 7, paragraph 0136. However, POMA renders the linker of present claim 51 obvious by teaching that “[f]lexible proteinaceous linkers can be chosen to increase the spatial separation between components and/or to allow for intramolecular interactions between components. For example, various "GS" linkers are known to the skilled worker and are composed of multiple glycines and/or serines, sometimes in repeating units, such as, e.g., (GxS)n, (SEQ ID NO: 203), (SxG)n (SEQ ID NO: 204), (GGGGS)n (SEQ ID NO: 205), and (G)n (SEQ ID NO: 206), in which x is 1 to 6 and n is 1 to 30” (see paragraph 0131).
Because the linkers of present SEQ ID NO: 39 of claim 51, SEQ ID NO: 18 of claim 52, and SEQ ID NO: 47 of claims 53 – 55 each falls within the conditions taught by POMA, POMA renders them obvious.
Response to Arguments
Page 19, last paragraph – p. 20, first paragraph of the reply of 09/02/2025 states that “Applicant submits that Poma does not cure the deficiencies in the combination of Addis and Conroy described above. That is, Poma does not teach or suggest the orientation of domains recited in claim 1. Claims 50-52 and 54 depend from claim 1. As such, all arguments advanced above with respect to claim 1 are equally applicable to claims 50-52 and 54.”
Applicant’s argument is not persuasive because ADDIS in view of CONROY renders the orientation of domains of the claimed binding molecule obvious as discussed above, and POMA teaches binding molecules having the limitations of claims 50 – 52 and 54. Thus, ADDIS in view of CONROY and in further view of POMA renders the inventions of claims 50 – 52 and 54 obvious for the reasons discussed above.
Previous rejection, maintained: claims 53 – 55 are rejected under 35 U.S.C. 103 as being unpatentable over ADDIS in view of CONROY as applied to claims 1, 48 – 49, 52, and 60 – 66 above, and further in view of CHANG (US 2020/0010566 A1, published 01/09/2020; see PTO-892).
The teachings of ADDIS and CONROY are discussed above and are fully incorporated here.
CHANG is directed to novel antibodies that specifically bind to GUCY2c and uses thereof in the treatment of cancer and novel bispecific antibodies comprising such antibodies and uses thereof in the treatment of cancer. See abstract. CHANG discloses antibodies with an Fc chain optimized to associate via a “knob-in-hole” association, where the Fc chain is connected to a VH via a linker. See paragraph 0066 and FIGS.1A, 1B, 1C and 1D. CHANG further discloses that the variable regions and constant domains may be either directly linked to one another or may be linked by a full or partial hinge or linker region.
Regarding claims 53 – 55, CHANG discloses present SEQ ID NOs: 47 and 44 . See TABLE 38 (SEQ ID NO: 190 and 195, respectively).
Because ADDIS and CONROY renders a multi-domain, single chain binding molecule obvious as discussed above and CHANG discloses linkers useful in linking Fc domains, especially those involving knob-in-hole technology, in binding molecules that treat cancer, it would have been obvious to modify ADDIS and CONROY’s binding molecule with CHANG’s linkers to arrive to the inventions of claims 53 – 55.
Response to Arguments
Page 20, fourth paragraph, of the reply of 09/02/2025 states that “Applicant submits that Chang does not cure the deficiencies in the combination of Addis and Conroy described above. That is, Chang does not teach or suggest the orientation of domains recited in claim 1. Claims 53-55 depend from claim 1. As such, all arguments advanced above with respect to claim 1 are equally applicable to claims 53-55.”
Applicant’s argument is not persuasive because ADDIS in view of CONROY renders the orientation of domains of the claimed binding molecule obvious as discussed above, and CHANG teaches binding molecules having the limitations of claims 53 – 55. Thus, ADDIS in view of CONROY and in further view of CHANG renders the inventions of claims 53 – 55 obvious for the reasons discussed above.
Previous rejection, maintained: claim 57 is rejected under 35 U.S.C. 103 as being unpatentable ADDIS in view of CONROY as applied to claims 1, 48 – 49, 52, and 60 – 66 above, and further in view of CAMPBELL (WO 2020/247867 A2, published 12/10/2020; see PTO-892).
The teachings of ADDIS and CONROY are discussed above and are fully incorporated here.
CAMPBELL is directed to modified T cell engagers, which are modified with a peptide and a half-life extending molecule and target tumor cell antigens. See abstract and paragraph 0004. CAMPBELL discloses a soluble, single chain TCR comprising a variable region of a TCR alpha extracellular domain, or fragment thereof, and a variable region of a TCR beta extracellular domain, or fragment thereof. See paragraph 0099. Furthermore, CAMPBELL discloses that an scFv is linked to the soluble TCR wherein the scFv comprises a light chain variable domain and heavy chain variable domain and the scFv binds to an effector cell antigen such as CD3. See p. 2, first sentence and p. 3, top paragraph.
Regarding claim 57, CAMPBELL discloses the sequences of SEQ ID NOs: 31 and 32 with 100% identity. See Appendix of record.
Because ADDIS and CONROY renders a multi-domain, single chain binding molecule obvious as discussed above and CAMPBELL discloses a CD3 immune effector domain that was successful in treating cancer, it would have been obvious to modify ADDIS and CONROY’s binding molecule with CAMPBELL’s CD3 immune effector domain to arrive to the invention of claim 57.
Response to Arguments
Page 20, last paragraph – p. 21, first paragraph, of the reply of 09/02/2025 states that “Applicant submits that Campbell does not cure the deficiencies in the combination of Addis and Conroy described above. That is, Campbell does not teach or suggest the orientation of domains recited in claim 1. Claim 57 depends from claim 1. As such, all arguments advanced above with respect to claim 1 are equally applicable to claim 57.”
Applicant’s argument is not persuasive because ADDIS in view of CONROY renders the orientation of domains of the claimed binding molecule obvious as discussed above, and CAMPBELL teaches binding molecules having the VL and VH of present claim 57. Thus, because CAMPBELL’s binding molecule is effective at treating cancer, it would have been obvious to use CAMPBELL’s VL and VH in ADDIS and CONROY’s multidomain binding molecule.
Previous rejection, maintained: claim 58 is rejected under 35 U.S.C. 103 as being unpatentable ADDIS in view of CONROY as applied to claims 1, 48 – 49, 52, and 60 – 66 above, and further in view of WELLS (WO 2021/087338 A1, published 05/06/2021; see PTO-892).
The teachings of ADDIS and CONROY are discussed above and are fully incorporated here.
WELLS is directed to bispecific binding agents and engineered transmembrane proteins, immunoconjugates, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating an activity of a cell and/or for the treatment of various diseases such as cancers. See abstract.
Regarding claim 58, WELLS discloses the sequences of SEQ ID NOs: 42 and 43 with 100% identity. See Appendix of record.
Because ADDIS in view of CONROY renders a multi-domain, single chain binding molecule obvious as discussed above and WELLS discloses an Fc domain that was successful in treating cancer, it would have been obvious to modify ADDIS and CONROY’s binding molecule with WELLS’ Fc domain to arrive to the invention of claim 58.
Response to Arguments
Page 21, fourth paragraph, of the reply of 09/02/2025 states that “Applicant submits that Wells does not cure the deficiencies in the combination of Addis and Conroy described above. That is, Wells does not teach or suggest the orientation of domains recited in claim 1. Claim 58 depends from claim 1. As such, all arguments advanced above with respect to claim 1 are equally applicable to claim 58.”
Applicant’s argument is not persuasive because ADDIS in view of CONROY renders the orientation of domains of the claimed binding molecule obvious as discussed above, and WELLS teaches binding moleculeS having the Fc sequences of present claim 58. Thus, because WELLS’ binding molecule is effective at treating cancer, it would have been obvious to use WELLS’ sequence in ADDIS and CONROY’s multidomain binding molecule.
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.
Previous rejection, maintained: claims 1, 47 – 55, 57 – 58, and 60 - rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 17 of U.S. Patent No. 11,718,657 in view of ADDIS, CONVOY, VOGELSTEIN, POMA, CHANG, CAMPBELL, and WELLS.
Patented claim 1 recites a soluble T cell receptor (TCR), comprising: a TCR alpha chain variable domain and a TCR beta chain variable domain, wherein each variable domain comprises FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4 where FR is a framework region and CDR is a complementarity determining region, wherein the soluble TCR has one of the following combinations of alpha chain and beta chain CDRs:
Alpha CDR1 CDR2 CDR3: . . . 7 TISGTDY (SEQ ID NO: 39) GLTSN (SEQ ID NO: 40) CILILGHSRLGNYIATF (SEQ ID NO: 40) . . .
nd wherein the soluble TCR has the property of binding to SLLQHLIGL (SEQ ID NO: 1) HLA-A*02 complex.
The main difference between the present claims and patented claims is that the present claims recite a CD3 immune effector domain, an Fc domain, and some of the sequences of the present claims. However, ADDIS, CONVOY, VOGELSTEIN, POMA, CHANG, CAMPBELL, and WELLS disclose this difference. The teachings of ADDIS, CONVOY, VOGELSTEIN, POMA, CHANG, CAMPBELL, and WELLS and how they relate to the claims, are set forth in the rejections under 35 U.S.C. 103 above.
Because the patented claims recite modified binding molecule (TCR domain) that binds to SLLQHLIGL of present claim 1, ADDIS and CONVOY and teach the addition of the CD immune effector and FC domains to form a multi-domain, single-chain binding molecule, and VOGELSTEIN, POMA, CHANG, CAMPBELL, and WELLS disclose some the sequences of the dependent claims above, it would have been obvious to one having ordinary skill in the art to use the patented claims’ modified TCR in the multi-domain, single-chain binding molecule of the present claims.
Previous rejection, maintained: claims 1, 47 – 55, 57 – 58, and 60 - rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 22 of U.S. Patent No. 12,018,062 in view of ADDIS, CONVOY, VOGELSTEIN, POMA, CHANG, CAMPBELL, and WELLS.
Patented claim 1 recites a heterodimeric TCR-anti-CD3 antibody fusion molecule, comprising a first polypeptide chain that comprises a TCR alpha chain variable domain and a second polypeptide chain that comprises a TCR beta chain variable domain, wherein: . . . the alpha chain variable domain has the amino acid sequence set forth in SEQ ID NO: 7 and the beta chain variable domain has the amino acid sequence set forth in SEQ ID NO: 17; . . .
Patented claim 11 recites that the heterodimeric TCR-anti-CD3 antibody fusion molecule of claim 10, wherein the anti-CD3 antibody is an scFv having the amino acid sequence of residues 1-253 of SEQ ID NO: 26, residues 1-253 of SEQ ID NO: 28, or residues 1-253 of SEQ ID NO: 30.
Patented SEQ ID NO: 7 discloses the CDRs of present SEQ ID NOs: 3 – 5 of present claim 1. Patented SEQ ID NO: 17 discloses the CDRs of present SEQ ID NO: 9 – 11 of present claim 1. Patented SEQ ID NO: 26, 28, and 30 each discloses the CDRs of present claim 47. See Appendix of record.
The main difference between the present claims and patented claims is that the present claims recite the binding to SLLQHLIGL (SEQ ID NO: 1) and the addition of an Fc domain, and some of the sequences of the present claims. However, ADDIS, CONVOY, VOGELSTEIN, POMA, CHANG, CAMPBELL, and WELLS disclose this difference. The teachings of ADDIS, CONVOY, VOGELSTEIN, POMA, CHANG, CAMPBELL, and WELLS and how they relate to the claims, are set forth in the rejections under 35 U.S.C. 103 above.
Because the patented claims recite a heterodimeric TCR-anti-CD3 antibody fusion molecule, ADDIS and CONVOY teach the binding of the fusion molecule to SLLQHLIGL (SEQ ID NO: 1) and the addition of an Fc domain to the fusion molecule, and VOGELSTEIN, POMA, CHANG, CAMPBELL, and WELLS disclose some the sequences of the dependent claims above, it would have been obvious to one having ordinary skill in the art to use the patented claims’ modified TCR in the multi-domain, single-chain binding molecule of the present claims.
Previous rejection, maintained: claims 1, 47 – 55, 57 – 58, and 60 – 66 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 42 – 69 of copending Application No. 18/664,825 in view of ADDIS, CONVOY, VOGELSTEIN, POMA, CHANG, CAMPBELL, and WELLS.
Copending claim 1 recites a heterodimeric T cell receptor (TCR)-anti-CD3 fusion molecule comprising a first polypeptide chain that comprises a TCR alpha chain variable domain.
Copending claim 48 recites a heterodimeric T cell receptor (TCR)-anti-CD3 antibody fusion molecule, comprising:a first polypeptide chain that has the amino acid sequence set forth in SEQ ID NO: 25 and a second polypeptide chain that has the amino acid sequence set forth in SEQ ID NO: 26; or a first polypeptide chain that has the amino acid sequence set forth in SEQ ID NO: 27 and a second polypeptide chain that has the amino acid sequence set forth in SEQ ID NO: 28.
Copending claim 51 recites pharmaceutical composition comprising a T cell receptor (TCR)-anti-CD3 fusion molecule comprising a soluble heterodimeric TCR and an anti-CD3 antibody or anti-CD3 binding, together with one or more pharmaceutically acceptable excipients, wherein the heterodimeric TCR comprises:(a) a first polypeptide chain comprising a TCR alpha variable domain having the amino acid sequence of SEQ ID NO: 7; and (b) a second polypeptide chain comprising a TCR beta variable domain having the amino acid sequence of SEQ ID NO: 17.
Copending SEQ ID NO: 26, 28, and 30 each discloses the CDRs of present claim 47. Copending SEQ ID NO: 7 discloses the CDRs of present SEQ ID NOs: 3 – 5 of present claim 1. Copending SEQ ID NO: 17 discloses the CDRs of present SEQ ID NO: 9 – 11 of present claim 1. See Appendix of record.
The main difference between the present claims and copending claims is that the present claims recite the binding to SLLQHLIGL (SEQ ID NO: 1) and the addition of an Fc domain, and some of the sequences of the present claims. However, ADDIS, CONVOY, VOGELSTEIN, POMA, CHANG, CAMPBELL, and WELLS disclose this difference. The teachings of ADDIS, CONVOY, VOGELSTEIN, POMA, CHANG, CAMPBELL, and WELLS and how they relate to the claims, are set forth in the rejections under 35 U.S.C. 103 above.
Because the copending claims recite a heterodimeric T cell receptor (TCR)-anti-CD3 fusion molecule, ADDIS and CONVOY teach the binding of the molecule to SLLQHLIGL (SEQ ID NO: 1) and the addition of an Fc domain, and VOGELSTEIN, POMA, CHANG, CAMPBELL, and WELLS disclose some the sequences of the dependent claims above, it would have been obvious to one having ordinary skill in the art to use the copending claims’ heterodimeric TCR-anti-CD3 fusion molecule in the multi-domain, single-chain binding molecule of the present claims.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
On page – of the reply of 09/02/2025, “Applicant respectfully requests that the nonstatutory double patenting rejections be reconsidered in view of the arguments presented herein.” All of Applicant’s arguments have been fully considered as discussed above but not found persuasive. Thus, the double patenting rejections are maintained.
Conclusion
Claims 1 and 47 – 66 are rejected.
THIS ACTION IS MADE FINAL. 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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/ESTELLA M. GUSTILO/Examiner, Art Unit 1646 /PETER J REDDIG/Primary Examiner, Art Unit 1646