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 .
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The present application is drawn from PCT/US2020/036464, filed 6/5/2020; and claims benefit under 35 U.S.C. 119(e) to U.S. Provisional applications 62/858509, filed 6/7/2019, and 62/858630, filed 6/7/2019.
Election/Restrictions
Applicant’s election without traverse of Group I, encompassing claims 1-23, in the reply filed on 10/24/2025 is acknowledged. Claims 24-25 and 27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Groups II-IV, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/21/2024. Applicant’s election of species, whereby the linker L3 is at least 10 amino acids, whereby the VH1 and VL1 comprise SEQ ID NOs: 44 and 45, respectively, whereby linkers L1, L2 and L3 are different lengths, and whereby L1 and L3 are the same length, is acknowledged. Claims 1-8, 11, 14-23 and 26 read on the elected species. Claim 13 does not read on the elected species because it requires L3 to be at least 15 amino acids in length and therefore is an alternate species from the elected species, whereby L3 is at least 10 amino acids. See election of species requirement of 4/25/2025, whereby the elected L3 corresponds to either claims 1-2 or claim 13. Applicants elected the species of claims 1-2.
Status of Claims
Claims 1-27 are pending; claims 9-10, 12-13, 24-25 and 27 are withdrawn; claims 1-8, 11, 14-23 and 26 are being examined on the merits.
Claim Objections
Claims 5 and 17 are objected to because of the following informalities: Claims 5 and 17 lack a period at the end of the claim. Appropriate correction is required.
Claim 21 is objected to because of the following informalities: Claim 21, lines 3-4, recite “nucleic acids encoding bispecific binding construct”. The phrase is missing an identifier (i.e., the, a) before the noun, which is the “bispecific binding construct”. Appropriate correction is required.
Claims 21-22 and 26 are objected to because of the following informalities: In the last line of amended claims 21-22 and 26, it reads “… construct of any of claim 1”. The phrase suggests reference to a plurality of claims, but only “claim 1” is recited. Applicants should delete the “any of” language in the cited claims, and any other claims that recite “any of” in reference to singular “claim 1”. Appropriate correction is required.
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.
Claims 1-2, 8, 11, 14-23 and 26 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Ghayur et al., (from IDS of 6/9/2025, FOR Cite No. 1; WO 2014/106015; published 7/3/2014).
Ghayur teaches multivalent binding proteins that specifically bind to one or more target antigens, as well as nucleic acids, vectors and host cells encoding the binding proteins and methods of using the binding proteins (abstract). Ghayur teaches making single-chain dual variable domain immunoglobulin molecules, termed scDVD, which have the general formula of VH1-X1-VH2-X2-VL1-X3-VL2; whereby X1, X2 and X3 are linkers (pg. 12, last paragraph – pg. 13, top). In example 17 (pg. 98), Ghayur teaches the design of an exemplary scDVD molecule, which is schematically depicted in FIG. 4. Ghayur teaches the X2 linker, which links the VH1/VH2 to the VL1/VL2, is a (G4S)n peptide linker of 30, 35, 40 or 45 amino acids in length (pg. 98, para. 1). Ghayur teaches the X1 and X3 linkers were selected from those presented in FIG. 5; whereby the SL linkers correspond to the first 6-14 amino acids of the IgG1 constant region and/or the first 6-14 amino acids of the IgK constant region (pg. 98, para. 2). Figure 5 displays the format of the binding protein being a VH1/VH2 polypeptide linked to a VL1/VL2 polypeptide by a (G4S)n linker; and wherein the SL 12_VH linker (ASTKGPSVFPLA) connects the VH1 to VH2; and the SL 12_VL linker (TVAAPSVFIFPP) connects the VL1 to VL2. Ghayur teaches two embodiments of the bispecific binding protein, whereby the first is a DLL4/VEGF scDVD and the second is a TNF/SOST scDVD (Example 19, pg. 99, para. 3).
Regarding claim 1-2, 8, 11 and 14-17; Ghayur teaches a TNF/SOST scDVD, whereby the binding protein targets TNF, which is expressed on the surface of T cells, and thus constitutes an immune effector cell target, and SOST (i.e. Sclerostin), which is expressed on target cells. Ghayur teaches the construct comprises a L1 that is 12 amino acids, a L2 that is 30 amino acids, and a L3 that is 12 amino acids. Thus, the scDVD of Ghayur anticipates the binding construct of instant claims 1-2, 8 and 11. Further, as the scDVD format of Ghayur anticipates the format of the instant binding constructs of claim 1-2, it necessarily possesses the inherent properties of instant claims 14-15. Further, as the TNF binding domain of the TNF/SOST can target transmembrane TNF expressed on T cells, and mature T cells necessarily express a T cell receptor (TCR), which necessarily includes expression of CD3ε, the TNF/SOST scDVD of Ghayur, by virtue of targeting TNF on T cells, anticipates instant claims 16-17.
Regarding claims 18-21 and 26; Ghayur teaches polynucleotides encoding the binding protein, expression vectors comprising the polynucleotides, host cells expressing the binding protein, and methods of manufacturing the binding protein (pg. 211, claims 37-40; see also pg. 49, section IV). Therefore, Ghayur anticipates instant claims 18-21. Ghayur also teaches pharmaceutical compositions comprising the binding protein (pg. 211, claim 35; see also pg. 58, section VI); thus Ghayur anticipates instant claim 26.
Regarding claims 22-23; Ghayur teaches methods of treatment comprising administering the binding protein (pg. 50, section V), whereby the antibody can be used for treating oncological disorders, including various types of cancers (pg. 58, paras. 1-2). Thus, Ghayur anticipates instant claim 22. Further, Ghayur teaches combination therapy (pg. 60, section VII), whereby the binding protein is administered with one or more additional therapeutic agents including antineoplastic agents or radiotherapy (pg. 60, para. 3). Thus, Ghayur anticipates instant claim 23.
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.
Claims 1-8, 11, 14-23 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Ghayur et al., (from IDS of 6/9/2025, FOR Cite No. 1; WO 2014/106015; published 7/3/2014) and Raum et al., (US Patent 10294300; issued 5/21/2019).
The reasons why Ghayur et al. anticipates instant claims 1-2, 8, 11, 14-23 and 26 are described above. However, Ghayur does not teach whereby the binding construct further comprises a half-life extending moiety following VL2, or wherein the half-life extending moiety comprises a single chain Fc domain and an additional linker (i.e. claims 3-4); nor does Ghayur teach a binding domain comprising the VH and VL of instant claim 7.
Raum teaches antibody constructs for DLL3 and CD3 (title). Raum teaches the CD3 binding domain is denominated as I2C (col. 68, lines 39-40). Raum teaches a DLL3 scFv construct of SEQ ID NO: 437 (col. 147), which comprises the VH of SEQ ID NO: 435 and the VL of SEQ ID NO: 436. The VH of Raum SEQ ID NO: 435 is 100% identical to the VH of instant SEQ ID NO: 44, and the VL of Raum SEQ ID NO: 436 is 100% identical to the VL of instant SEQ ID NO: 45. Further, Raum teaches the bispecific construct of SEQ ID NO: 438 is a DLL3 x I2C bispecific molecule (i.e. DLL3 x CD3). Raum SEQ ID NO: 438 comprises the DLL3 VH and VL of instant SEQ ID NOs: 44-45, and further comprises the I2C VH and VL of instant SEQ ID NOs: 50-51, respectively, with 100% sequence identity. Therefore the bispecific construct of Raum SEQ ID NO: 438 comprises a DLL3 scFv and a CD3 scFv, however in the (scFv)2 format of VH1-L1-VL1-L2-VH2-L3-VL2; whereby L1 and L3 are (G4S)3 linkers which are each 15 amino acids in length. The L2 is a (G4S)1 which is 5 amino acids in length.
It would have been obvious to one of skill in the art to modify the TNF/SOST scDVD binding protein format of Ghayur to instead comprise the DLL3/CD3 variable domains of Raum et al. One would have been motivated to do so given that each combination results in a bispecific binding protein that targets an immune effector cell and a target cell for the purpose of treating cancer; and that scDVD format, VH1-L1-VH2-L2-VL1-L3-VL2, provides an improved multispecific binding protein format, as taught by Ghayur et al. There would have been a reasonable expectation of success given that various corresponding VH/VL domains may be used in the scDVD format, and that the linkers, specifically the longer L2 linker, are what imparts the ability of the corresponding VH1/VL1 and VH2/VL2 pairs to form their functional binding domains at the level of the target antigen, as taught by Ghayur et al. Ghayur demonstrates the success of the scDVD format with 2 separate embodiments, one a TNF/SOST bispecific molecule, the other a DLL4/VEGF bispecific molecule, thus providing a reasonable expectation for success of scDVD formats when incorporating VH/VL domains with distinct target specificity. Thus, the invention was prima facie obvious to one of skill in the art at the time the invention was made.
Regarding claims 1 and 6-7; the combination bispecific binding protein of Ghayur and Raum comprises the anti-DLL3 VH1 and VL1 of Raum and the anti-CD3 VH2 and VL2 of Raum, in the VH1-L1-VH2-L2-VL1-L3-VL2 scDVD format of Ghayur. Wherein the L1 is the SL 12_VH linker (ASTKGPSVFPLA); the L3 is the SL 12_VL linker (TVAAPSVFIFPP); and the L2 is the (G4S)n peptide linker of 30, 35, 40 or 45 amino acids in length, as taught by Ghayur et al. Therefore the combination binding protein of Ghayur and Raum makes obvious the bispecific binding construct of instant claim 1; and wherein the VH1, VH2, VL1 and VL2 all have different sequences of instant claim 6; and wherein the VH1 and VL1 are SEQ ID NOs: 44-45 and the VH2 and VL2 are SEQ ID NOs: 50-51, of instant claim 7.
Regarding claims 3-5. The instant specifications teach that the half-life extending moiety is an Fc region, which can be located at the C-terminal end of the HHLL bispecific binding construct, and that the Fc utilized for half-life extension can be a single chain Fc (instant specs., paras. 0072-0073); which may be a single chain polypeptide extending from the N-terminal hinge region to the native C-terminus of the Fc region of a human IgG1 antibody (para. 0078). Further, that sequences of IgG1 that can be used include SEQ ID NO: 36 (para. 0075; Table 2), which includes the CH2 and CH3 regions (i.e. excluding the hinge region) from position 231-447 (para. 0076). Thus, the instant specs teach that suitable half-life extending moiety includes a single chain IgG1 Fc polypeptide encompassing residues 231-447 of instant SEQ ID NO: 36. Raum et al. teaches a “mono Fc” polypeptide of SEQ ID NO: 341 (col. 137), which is 100% identical in amino acid sequence to residues 231-447 of instant SEQ ID NO: 36. Regarding the “mono Fc” of Raum SEQ ID NO: 341, Raum teaches in a preferred embodiment, the bispecific antibody constructs may be linked with a polypeptide for the purpose of extending the construct’s serum half-life (Raum, col. 26, lines 1-6). Further, that the polypeptides may comprise an antibody derived Fc region, whereby exemplary sequences include SEQ ID NO: 341, whereby the polypeptide may be linked to the C-terminus of the bispecific antibody construct, and whereby it is linked through a peptide linker such as (G4S)n (col. 26, lines 9-16).
Thus, Raum teaches a “single chain Fc” (i.e. mono Fc) polypeptide of IgG1 may be linked to the C-terminus of the bispecific binding construct, by a linker, for the purpose of extending the half-life of the binding construct. Therefore, the combination bispecific construct of Ghayur and Raum make obvious instant claims 3-4. Regarding claim 5, Raum also teaches methods of extending the half-life of the antibody constructs includes linking variants of the Fc domains, which may be optimized or modified in order to, for example, abolish Fc receptor binding, such as binding to the Fcγ receptor (Raum, col. 25, lines 60-64). Raum teaches an exemplary species of the polypeptide that may be linked to the bispecific antibody construct, alternative to SEQ ID NO: 341, is SEQ ID NO: 340 (col. 26, lines 9-12; col. 137). The polypeptide of SEQ ID NO: 340 is identical to the mono Fc of SEQ ID NO: 341, except that it includes the hinge region (i.e. residues 216-230 of instant SEQ ID NO: 36, specs., pg. 19-20, para. 0076), and it has 3 residue substitutions, including LALA mutations at residues 234-235 (residues according to the full IgG1; corresponding to residues 4-5 of SEQ ID NO: 341). This modification is consistent with the modifications taught in the instant specifications, (see pg. 22, para. 0082, L234A/L235A). Therefore, Raum teaches a mono Fc polypeptide, with LALA mutations, which may be attached to the bispecific molecule for the purposes of extending half-life; and thus the combination of Ghayur and Raum make obvious instant claim 5.
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.
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Claims 1-6, 8, 11, 14-23 and 26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 and 14-32 of copending Application No. 17/616,575 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the scope of the claims of application ‘575 anticipate that of the instant claims.
Application ‘575 claims a bispecific construct with the format of VH1-L1-VH2-L2-VL1-L3-VL2, with linkers L1, L2 and L3, whereby L1 is 10 aa, L2 is at least 15 aa, and L3 is at least 10 aa, wherein L1 or L3 comprises a protease cleavage site (claim 1), or wherein the protein also comprises a scFc subdomain (claim 2), wherein L1 and L3 each comprise a protease cleavage site (claim 3), whereby the protein further comprises a half-life extending moiety (claim 8), which is a single chain Fc from IgG1, and an additional linker (claim 9), whereby the additional linker comprises a cleavage site (claim 10), wherein the scFc polypeptide comprises an alteration (claim 11), whereby the VH1, VH2, VL1 and VL2 have different sequences (claim 12), whereby the linkers are of different length (claim 17), wherein the L1 and L3 linkers are the same length (claim 20), whereby the effector cell expresses a protein that is part of a TCR (claim 23), wherein the protein is CD3ε (claim 24), including nucleic acids, vectors and host cells (claims 25-27), as well as a method for manufacturing the protein (claim 28) and a method for treating cancer (claim 29), including an additional chemotherapeutic agent (claim 30); as well as a pharmaceutical composition comprising the protein (claim 31). Application ‘575 dependent claims 4-7, 14-16, 18-19, 21-22 and 32 also encompass the limitations cited above, and thus also read on the instant claims.
Specifically, the bispecific binding construct of app ‘575 claims 1-3 anticipates instant claims 1-2 and the inherent properties of instant claims 14-15; app ‘575 claim claims 8-11 anticipate instant claims 3-5; app ‘575 claim 12 anticipates instant claim 6; app ‘575 claims 17 and 20 anticipate instant claims 8 and 11; app ‘575 claims 23-24 anticipate instant claims 16-17; app ‘575 claims 25-28 anticipate instant claims 18-21; and app ‘575 claims 29-31 anticipate instant claims 22-23 and 26.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-8, 11, 14-23 and 26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 and 14-32 of copending Application No. 17/616,575 in view of Raum et al., (US Patent 10294300; issued 5/21/2019).
The reasons why claims 1-6, 8, 11, 14-23 and 26 are anticipated by claims 1-3, 8-12, 17, 20 and 23-31, and dependent claims 4-7, 14-16, 18-19, 21-22 and 32, of application ‘575 are described above. However, app ‘575 does not teach wherein the VH1 and VL1 are of SEQ ID NOs: 44-45, respectively, and the VH2 and VL2 are of SEQ ID NOs: 50-51, respectively (i.e., claim 7).
Raum et al. teaches bispecific binding proteins with the (scFv)2 format, as described above. Raum teaches one such format is SEQ ID NO: 438, which is a DLL3/CD3 bispecific binding construct. SEQ ID NO: 438 of Raum comprises the DLL3 VH and VL domains of instant SEQ ID NOs: 44-45, respectively, and also comprises the CD3 VH and VL domains of instant SEQ ID NOs: 50-51, respectively, with 100% sequence identity, as described above.
It would have been obvious to one of skill in the art to utilize the DLL3 VH1 and VL1, and the CD3 VH2 and VL2, of Raum et al., in the binding construct format of app ‘575. One would be motivated to do so in order to target the binding construct to CD3 on an immune effector cell and to DLL3 on a target cell, as taught by Raum et al. There would have been a reasonable expectation for success given that the linkers, L1-L3, and specifically the long L2 linker, allows the corresponding VH1/VL1 and VH2/VL2 domains to form a functional binding domain at the level of the target antigen, and that variable domains, with different target specificities, are substitutable in a bispecific construct with the VH1-L1-VH2-L2-VL1-L3-VL2 format. Thus the invention was prima facie obvious to one of skill in the art at the time the invention was made.
As such, the VH1, VL1, VH2, VL2 binding domains of Raum, in the format of the bispecific binding protein of app ‘575 claim 1, makes obvious instant claim 7.
This is a provisional nonstatutory double patenting rejection.
Claims 1-6, 8, 11, 14-18, 21-23 and 26 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, 4-6, 8, 11, 14-17, 21-23 and 26 of copending Application No. 18/038,886 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the scope of the claims of application ‘886 anticipate that of the instant claims.
Application ‘886 claims a molecule having the structure VH1-L1-VH2-L2-VL1-L3-VL2-L4-Half-Life Extending moiety-L5-VH3-L1-VH4-L2-VL3-L3-VL4; wherein each linker (L1-L3) are at least 10 amino acids and total at least 35 amino acids, and wherein the half-life extending moiety is a single chain Fc (scFc) region (claim 2); wherein the half-life moiety is an scFc from IgG1 (claim 4); wherein the scFc comprises alterations that inhibit Fcγ binding (claim 5); wherein the VH1, VH2, VL1 and VL2 all have different sequences (claim 6); wherein the L1, L2 and L3 are different lengths (claim 8); wherein the L1 and L3 are the same length (claim 11); whereby the molecule exhibits enhanced stability (claim 14), and exhibits enhanced in vitro expression (claim 15); whereby the effector cell expresses a TCR (claim 16); wherein the effector cell protein is CD3ε (claim 17). App ‘886 also claims a method of manufacturing comprising nucleic acids encoding the molecule in a host cell expressing the molecule (claim 21), a method of treating a cancer patient (claim 22); whereby a additional chemotherapeutic agent is administered (claim 23); and a pharmaceutical composition comprising the molecule (claim 26).
While the construct of app ‘886 includes additional variable domain moieties beyond what is required in the instant claims, it nonetheless comprises the VH1-L1-VH2-L2-VL1-L3-VL2 format of the instant bispecific binding construct; it comprises the format twice in the same construct (with or without a half-life extending moiety). Therefore, app ‘886 claims 2 and 4-6 anticipate instant claims 1-6; app ‘886 claims 8, 11 and 14-15 anticipate instant claims 8, 11 and 14-15; app ‘886 claims 16-17 anticipate instant claims 16-17; the method of manufacturing of app ‘886 claim 21 anticipates the nucleic acids and the methods of instant claims 18 and 21; the methods of treating cancer of app ‘886 claims 22-23 anticipate the methods of instant claims 22-23; and app ‘886 claim 26 anticipates instant claim 26.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-6, 8, 11, 14-23 and 26 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, 4-6, 8, 11, 14-17, 21-23 and 26 of copending Application No. 18/038,886 in view of Law et al., (US 2011/0311550; published 12/22/2011).
The reasons why the claims of application ‘886 anticipate instant claims 1-6, 8, 11, 14-18, 21-23 and 26 are described above. However, app ‘886 does not claim a vector comprising the nucleic acids encoding the bispecific binding construct (i.e., claims 19-20).
Law et al. teaches the art of engineering antibodies, including methods for producing polypeptides and antibodies (pg. 39, para. 0253). Law teaches generating nucleic acids encoding the polypeptides (pg. 39, para. 0258), as well as methods of selecting the appropriate expression vectors for packaging the nucleic acid (pg. 54, para. 0264). Law also teaches identifying appropriate cell expression systems (pg. 55, para. 0273), whereby the host cells contain the vectors and nucleic acids encoding the polypeptide.
It would have been obvious to one of skill in the art to package the nucleic acids encoding the polypeptide, of app ‘886, into an expression vector and to introduce the expression vector into host cells for the purpose of expressing and manufacturing the polypeptide. One would have been motivated to do so to manufacture the polypeptide consistent with the method of manufacturing the molecule as claimed in app ‘886, claim 21. There would have been a reasonable expectation for success given that packaging nucleic acids in expression vectors and introducing the vectors in host cells are common techniques in the art of generating polypeptides, as taught by Law et al. Thus, the claims were prima facie obvious at the time of the invention.
Specifically, app ‘886, claim 21, in view of Law et al., make obvious instant claims 19-20.
This is a provisional nonstatutory double patenting rejection.
Claims 1- 8, 11, 14-18, 21-23 and 26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, 4-6, 8, 11, 14-17, 21-23 and 26 of copending Application No. 18/038,886 in view of Raum et al., (US Patent 10294300; issued 5/21/2019).
The reasons why the claims of application ‘886 anticipate instant claims 1-6, 8, 11, 14-18, 21-23 and 26 are described above. However, app ‘886 does not teach wherein the VH1 and VL1 are of SEQ ID NOs: 44-45, respectively, and the VH2 and VL2 are of SEQ ID NOs: 50-51, respectively (i.e., claim 7).
Raum et al. teaches bispecific binding proteins with the (scFv)2 format, as described above. Raum teaches one such format is SEQ ID NO: 438, which is a DLL3/CD3 bispecific binding construct. SEQ ID NO: 438 of Raum comprises the DLL3 VH and VL domains of instant SEQ ID NOs: 44-45, respectively, and also comprises the CD3 VH and VL domains of instant SEQ ID NOs: 50-51, respectively, with 100% sequence identity, as described above.
It would have been obvious to one of skill in the art to utilize the DLL3 VH1 and VL1, and the CD3 VH2 and VL2, of Raum et al., in the binding construct format of app ‘886. One would be motivated to do so in order to target the binding construct to CD3 on an immune effector cell and to DLL3 on a target cell, as taught by Raum et al. There would have been a reasonable expectation for success given that the linkers, L1-L3, and specifically the long L2 linker, allows the corresponding VH1/VL1 and VH2/VL2 domains to form a functional binding domain at the level of the target antigen, and that variable domains, with different target specificities, are substitutable in a bispecific construct with the VH1-L1-VH2-L2-VL1-L3-VL2 format. Thus, the invention was prima facie obvious to one of skill in the art at the time the invention was made.
As such, the VH1, VL1, VH2, VL2 binding domains of Raum, in the format of the bispecific binding protein of app ‘886 claim 1, makes obvious instant claim 7.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
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/JAMES RYLAND MELCHIOR/Examiner, Art Unit 1644
/DANIEL E KOLKER/Supervisory Patent Examiner, Art Unit 1644