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 .
Applicant’s remarks, filed 9/26/2025, are acknowledged and entered into the record.
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 a continuation of PCT/US2024/045722, filed 9/6/2024; and claims benefit under 35 U.S.C. 119(e) to U.S. Provisional application 63/536921, filed 9/6/2023.
Election/Restrictions
Applicant's election with traverse of Group I, encompassing claims 1-17 and 22, in the reply filed on 9/26/2025 is acknowledged. The traversal is on the ground(s) that the search of the product polypeptides will necessarily uncover the art related to the methods of treatment set forth in Group II (remarks, pg. 7), and that the classification of the molecules in Group I into class C07K is inappropriate because they could be classified in class A61K. Applicants point out that A61K covers both compositions and treatments, and that A61K relates to medicinal preparations containing antibodies and other compounds as active ingredients (remarks, pg. 7, bottom). This is not found persuasive because class A61K is drawn to compositions, including antibodies and “other active ingredients”; the invention of Group I is a product (i.e. a construct), not a composition, and not medicinal composition comprising other active ingredients. Methods claims must be examined based on the active steps of the methods, not just the limitations of the product used in the methods, and requires a different search strategy compared to product claims; this includes considerations regarding whether the methods are sufficiently described and properly enabled for one to make and use the invention. That is, while an antibody structure may be free of the art for a corresponding structure, use of that antibody for treating a viral infection versus cancer, or for any type of cancer, or for any type of disease or disorder, or for in vitro diagnostic, screening, isolating or labeling assays, must be enabled in view of the state of the art. These aspects of search and examination of methods claims or how compositions are formulated, are significantly different than searching and examining a product’s structural limitations. Search burden is both the time and cost associated with examination of products versus compositions versus methods of use as medicinal preparations. The product of Group I is properly classified in C07K, while the methods are properly classified in A61K. Applicant’s arguments are not found persuasive and the requirement for restriction is maintained. Applicants are reminded that if the product of Group I is found to be allowable, the examiner will rejoin the methods claims of Group II, and will subsequently search and consider the invention of Group II. However, if the product of Group I is not deemed allowable, the invention of non-elected Group II will not be examined.
The requirement is still deemed proper and is therefore made FINAL. Claims 18 and 23, drawn to methods of treating cancer classified in A61K 39/00, are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group II , there being no allowable generic or linking claim. Applicant’s election of the species of TSB being for EGFR and the ICB being for CD3, in the remarks of 9/26/2025 is acknowledged. Claim 15 is withdrawn as being directed to a non-elected species.
Status of Claims
Claims 1-18 and 22-23 are pending, claims 1-14, 16-17 and 22 are being examined on the merits.
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.
Claims 6, 17 and 22 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 6 contains the trademark/trade name “Nanobody” in line 2. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe an alternative antibody binding domain format such as a single domain antibody (sdAb) and, accordingly, the identification/description is indefinite.
Claims 17 and 22 recite “free of detectable pyrogens” in line 3 of each claim. Determination of whether or not a solution is free of detectable pyrogens depends on the assay being used to measure detectable pyrogens. An insensitive assay may not detect pyrogens that are present but are below the threshold of detection, whereas a more sensitive assay might detect pyrogens in the same solution; and the threshold for detection is not a defined unit in the claim. That is, whether or not something is free of detectable pyrogens depends on the method of detection. Neither the method of detection, nor a defined limit on the concentration of pyrogens which would be considered “detectable” across all assays, is recited in the claims. Therefore, the person with ordinary skill in the art could not be sure whether or not they were free of infringement because the term “detectable” is relative. As the limits of the claim are unclear, the claim is rendered indefinite.
Claims 17 and 22 recite “an acceptable limit” in the last line of each claim. It is unclear what the defined limit of acceptable pyrogens is. What one person may consider unacceptable, another person may consider acceptable. Thus the term “acceptable” is relative, and the limit on what concentration of pyrogens in the solution would be “acceptable” is not defined. Thus, the person of ordinary skill in the art could not be sure whether or not they were free of infringement. As the metes and bounds of the claim are unclear, the claim is rendered indefinite.
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 1 and 8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 6-7, 10-12 and 14 of U.S. Patent No. 12,180,297; issued 12/31/2024. Although the claims at issue are not identical, they are not patentably distinct from each other because the scope of the claims of US Patent ‘297 anticipate that of the instant claims.
Instant claim 1 is drawn to a construct comprising a first HC constant region polypeptide sequence, which comprises a NBD joined by a linker, and a second HC constant polypeptide sequence, whereby the first and second HC constant polypeptides form an IgFc. Under the broadest reasonable interpretation, claim 1 encompasses an antibody Fc with an NBD joined, directly or indirectly via a linker, to the N-terminus or the C-terminus of one HC constant domain of the antibody. See instant Fig. 1B, left, whereby the NBD is linked to the C-terminal of an antibody HC Fc domain, or Fig 1C, whereby the NBD is linked to the N-terminal of an antibody HC Fc domain.
US Patent ‘297 claims a polypeptide construct comprising a NBD and a tumor specific binder (TSB), wherein the NBD comprises an ATP binding site and can dimerize with a cognate non-identical NBD sequence in the presence of ATP, and the TSB comprises a sequence of an antibody or antigen binding fragment thereof, and has affinity for a tumor associated antigen (TAA) expressed on the surface of a tumor cell (claim 1). US ‘297 also claims wherein the polypeptide construct comprises a scaffold sequence (claim 2), and a composition comprising the first polypeptide construct (claim 3); and whereby the first polypeptide sequence, in the composition, comprises a TSB which is an anti-EGFR antibody (claim 5); whereby the scaffold comprises an immunoglobulin sequence (claim 6), whereby the scaffold is an IgFc sequence (claim 7), whereby the NBD comprises a TAP1 amino acid sequence of SEQ ID NOs: 10 or 88 (claims 10-12). US ‘297 also claims the polypeptide construct as a monomer or dimer, and whereby the construct also comprises an immune cell engager (ICE) domain having affinity for CD3 (claim 14).
The NBD of ‘297 SEQ ID NOs: 10 and 88 are 100% identical to the NBD of instant SEQ ID NOs: 16 and 294, respectively, wherein the X688 residue is N; and thereby possess the inherent properties of binding ATP and dimerizing around ATP of the NBD of the first polypeptide of the composition of US ‘297.
Therefore, US ‘297 claims a first polypeptide construct that may comprise an NBD, a scaffold, a TSB and an ICE domain (claims 1 and 14). In an embodiment the TSB is a full length anti-EGFR antibody, with the NBD linked to a heavy chain N- or C-terminal of the anti-EGFR antibody. Such an embodiment comprises a first polypeptide encoding a first HC Fc scaffold domain and a second polypeptide encoding a second HC Fc scaffold domain, and whereby the first and second Ig HC constant regions form an IgFc (e.g., of the full length anti-EGFR antibody). Thus, US ‘297 claims 1-3, 6-7 and 10-12 anticipate instant claim 1, and US ‘297 claims 1-3, 6-7, 10-12 and 14 anticipate instant claim 8.
Claims 1-14, 16-17 and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 6-7, 10-12 and 14 of U.S. Patent No. 12,180,297; issued 12/31/2024 in view of Kontermann et al., (US 2022/0396635; published 12/15/2022).
The reasons why the polypeptides of US Patent ‘297 anticipate that of instant claims 1 and 8 are described above. Briefly, US ‘297 claims a first polypeptide that may have an NBD amino acid sequence, a TSB domain, and a ICE domain, and whereby the TSB domain may be a full anti-TAA antibody comprising an Ig Fc domain as a scaffold, whereby the Fc domain is a functional Fc domain. For example, an anti-EGFR antibody with a NBD sequence linked to the C-terminal of one Fc domain anticipates the construct of instant claim 1 (see instant Fig. 1B, left). However, US ‘297 does not claim whereby the scaffold comprises an KiH sequence pair, or whereby the polypeptide comprises a payload or label (i.e., claims 2, 4, 10-11, and dependents thereof).
Kontermann et al teaches trivalent binding molecules comprising a first polypeptide comprising two binding domains and a second polypeptide comprising a third binding domain (abstract). Kontermann teaches one binding domain is targeted to a tumor associated antigen, such as HER2, HER3 or EGFR (pg. 3, para. 0026), and the other binding domain targets the trigger molecule of the immune effector cell, for example, CD3 (pg. 2, para. 0025). Konetermann teaches that the binding molecules may also comprise one or more molecules that aid in purification, preferably a hexahistidyl-tag or FLAG-tag, and one or more co-stimulatory molecules, (pg. 3, paras. 0029-0030), including 4-1BBL (pg. 18, para. 0121), or one or more checkpoint inhibitors, including PD-L1 (pg. 18, para. 0121). Kontermann teaches the construct has heterodimerizing Fc, which includes “knob-into-hole” technology (pg. 15, para. 0092). Kontermann teaches the binding domains may be single-chain diabodies (scDb), which are 4 variable domains of two antibodies connected by 3 linkers, which can be employed for T-cell retargeting to tumor cells but also cells of the tumor microenvironment (pg. 18, para. 0122). Kontermann teaches one embodiment is a trivalent, bispecific anti-HER3 x anti-CD3 antibody (termed a scDb/scFv-Fc; Fig. 6), comprising a scDb molecule bispecific for HER3 (3-43) and CD3 (huU3, humanized version of UCHT1), and further comprising a scFv (or Fab) fragment specific for HER3 or CD3, and which utilized a heterodimerizing Fc part with knob-in-hole technology, of Fig. 6 (pg. 23, Example 5, para. 0205). Figure 6B displays the alternative formats of the two polypeptides of the construct; whereby one polypeptide comprises an Fc (hole) and the other polypeptide comprise an Fc (knob), such that the two polypeptides heterodimerize. The polypeptide with the Fc(hole) comprises a scDb with bispecific affinity for HER3 and CD3, while the polypeptide with the Fc(knob) comprises a N-terminal scFv directed at HER3. Kontermann teaches a similar embodiment which is an anti-EGFR x CD3 construct, whereby the EGFR-targeting antibody is centuximab, and follows the same format of the anti-HER3 x CD3 scDb/scFv-Fc construct; such that it comprises a scDb with binding affinity for EGFR and CD3 on one polypeptide with the Fc(hole), and an anti-EFGR scFv on the second polypeptide with the Fc(knob) mutation (pg. 24, Example 9, para. 0209). Kontermann teaches alternative formats including a trivalent, bispecific Fc fusion protein targeting EGFR, whereby the scDb may be monospecific for EGFR and the scFv (or Fab) for CD3 binding may be alternatively positioned as the scFv of the second polypeptide with the Fc(knob) mutation; with reference to Fig. 6 for an overview of formats (pg. 27, Example 11, para. 0217).
It would have been obvious to one of skill in the art to utilize the anti-EGFR/anti-CD3 construct of Kontermann as the TSB antibody domain of the first polypeptide construct of US ‘297. One would have been motivated to do so given that the anti-EGFR/anti-CD3 antibody targets the tumor associated antigen EGFR for the purpose of targeting the construct to the tumor or tumor microenvironment, as taught by Kontermann, where the NBD would bind (and dimerize around) the excessive ATP in the tumor microenvironment, as taught by US ‘297. There would have been a reasonable expectation for success given that US ‘297 teaches that the polypeptide comprising the NBD may also comprise the TSB amino acid sequence of an EGFR antibody, and that Kontermann teaches the anti-EGFR/anti-CD3 antibody construct successfully targets EGFR-expressing tumor cells. Thus, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made.
The combination construct of US ‘297 and Kontermann would comprise a first polypeptide comprising a Fc (knob) and the NBD of US ‘297 linked, directly or via a linker, to the C-terminal or N-terminal of the Fc (knob), and a second polypeptide comprising an Fc (hole) and an anti-EGFR/anti-CD3 bispecific scDb at the N-terminus, whereby the Fc domains form a heterodimer IgFc as a single construct. The construct comprising two polypeptides includes the interspecific amino acid sequence pair of knob-in-hole (KiH) sequences (re. claims 2-3). The construct may also include a 4-1BBL, as taught by Kontermann (pg. 18, para. 0121), which is a therapeutic agent (re. claim 4). The construct comprises an additional anti-EGFR scFv on the first polypeptide chain (re. claim 6).
Thus, the construct of the combination of US ‘297, claim 1, and Kontermann makes obvious the construct of instant claim 1, comprising an NBD of SEQ ID NO: 16 and two heavy chain constant regions comprising an Fc; wherein the Fc have KiH mutations of instant claims 2-3; wherein the construct comprises a therapeutic agent of instant claim 4; wherein the construct comprises an EGFR TSB of instant claims 5 and 7, which is an scFv of instant claim 6; whereby the construct comprises an NBD that can homodimerize and which comprises an anti-CD3 ICB of instant claim 8, whereby only one polypeptide comprises the NBD and the second polypeptide comprises the ICB of claim 9, with KiH mutations of instant claims 10 and 12, with a 4-1BBL therapeutic agent of claim 11, wherein the ICB targets CD3 of claims 13-14. The construct comprising the NBD, when bound to ATP, makes obvious the bound complex of instant claim 16. Kontermann teaches the construct may be formulated in a pharmaceutical composition comprising a pharmaceutically acceptable carrier, and thus makes obvious instant claims 17 and 22.
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-7 and 10-12 of copending Application No. 18/989,938 (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 ‘938 anticipate those of the instant claims.
App ‘938 claims a polypeptide construct comprising a NBD and a tumor specific binder (TSB), wherein the NBD comprises an ATP binding site and can dimerize with a cognate non-identical NBD sequence in the presence of ATP (claim 1). App ‘938 also claims wherein the polypeptide construct comprises a scaffold sequence (claim 2), and a composition comprising the first polypeptide construct (claim 3); and whereby the first polypeptide sequence, in the composition, comprises a TSB which is an anti-EGFR antibody (claim 5); whereby the scaffold comprises an immunoglobulin sequence (claim 6), whereby the scaffold is an IgFc sequence (claim 7), whereby the NBD comprises a TAP1 amino acid sequence of SEQ ID NOs: 10 or 88 (claims 10-12).
The NBD of app ‘938 SEQ ID NOs: 10 and 88 (of claim 12) are 100% identical to the NBD of instant SEQ ID NOs: 16 and 294, respectively, wherein the X688 residue is N; and thereby possess the inherent properties of binding ATP and dimerizing around ATP of the NBD of the first polypeptide of the composition of app ‘938.
Therefore, app ‘938 claims a first polypeptide construct that may comprise an NBD, a scaffold, and a TSB (claims 1-3 and 5). In an embodiment the TSB is a full length anti-EGFR antibody, with the NBD linked to a heavy chain N- or C-terminal of the anti-EGFR antibody. Such an embodiment comprises a first polypeptide encoding a first HC Fc scaffold domain and a second polypeptide encoding a second HC Fc scaffold domain, and whereby the first and second Ig HC constant regions form an IgFc (e.g., of the full length anti-EGFR antibody). Thus, app ‘938 claims 1-3, 5-7 and 10-12 anticipate instant claim 1.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-14, 16-17 and 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-7 and 10-12 of copending Application No. 18/989,938 in view of Kontermann et al., (US 2022/0396635; published 12/15/2022).
The reasons why the polypeptides of application ‘938 anticipate that of instant claim 1 are described above. App ‘938 claims a first polypeptide that may have an NBD amino acid sequence and a TSB domain, and whereby the TSB domain may be a full anti-TAA antibody comprising an Ig Fc domain as a scaffold, whereby the Fc domain is a functional Fc domain. For example, an anti-EGFR antibody with a NBD sequence linked to the C-terminal of one Fc domain anticipates the construct of instant claim 1 (see instant Fig. 1B, left). App ‘938 also claims a polypeptide construct with a NBD (of TAP1 or TAP2) and further comprising an immune cell engager (ICE) domain (claim 18), with a scaffold aa sequence (claim 19); and a composition comprising the first and second polypeptide constructs wherein the TSB of the first polypeptide binds EGFR and the ICE of the second polypeptide is a Fab or scFv with affinity for CD3 (claim 20). However, app ‘938 does not claim whereby the scaffold comprises an KiH sequence pair, or whereby the polypeptide comprises a payload or label (i.e., instant claims 2, 4, 8, 10-11, and dependents thereof).
Kontermann et al teaches trivalent binding molecules comprising a first polypeptide comprising two binding domains and a second polypeptide comprising a third binding domain (abstract). Kontermann teaches one binding domain is targeted to a tumor associated antigen, such as HER2, HER3 or EGFR (pg. 3, para. 0026), and the other binding domain targets the trigger molecule of the immune effector cell, for example, CD3 (pg. 2, para. 0025). Konetermann teaches that the binding molecules may also comprise one or more molecules that aid in purification, preferably a hexahistidyl-tag or FLAG-tag, and one or more co-stimulatory molecules, (pg. 3, paras. 0029-0030), including 4-1BBL (pg. 18, para. 0121), or one or more checkpoint inhibitors, including PD-L1 (pg. 18, para. 0121). Kontermann teaches the construct has heterodimerizing Fc, which includes “knob-into-hole” technology (pg. 15, para. 0092). Kontermann teaches the binding domains may be single-chain diabodies (scDb), which are 4 variable domains of two antibodies connected by 3 linkers, which can be employed for T-cell retargeting to tumor cells but also cells of the tumor microenvironment (pg. 18, para. 0122). Kontermann teaches one embodiment is a trivalent, bispecific anti-HER3 x anti-CD3 antibody (termed a scDb/scFv-Fc; Fig. 6), comprising a scDb molecule bispecific for HER3 (3-43) and CD3 (huU3, humanized version of UCHT1), and further comprising a scFv (or Fab) fragment specific for HER3 or CD3, and which utilized a heterodimerizing Fc part with knob-in-hole technology, of Fig. 6 (pg. 23, Example 5, para. 0205). Figure 6B displays the alternative formats of the two polypeptides of the construct; whereby one polypeptide comprises an Fc (hole) and the other polypeptide comprise an Fc (knob), such that the two polypeptides heterodimerize. The polypeptide with the Fc(hole) comprises a scDb with bispecific affinity for HER3 and CD3, while the polypeptide with the Fc(knob) comprises a N-terminal scFv directed at HER3. Kontermann teaches a similar embodiment which is an anti-EGFR x CD3 construct, whereby the EGFR-targeting antibody is centuximab, and follows the same format of the anti-HER3 x CD3 scDb/scFv-Fc construct; such that it comprises a scDb with binding affinity for EGFR and CD3 on one polypeptide with the Fc(hole), and an anti-EFGR scFv on the second polypeptide with the Fc(knob) mutation (pg. 24, Example 9, para. 0209). Kontermann teaches alternative formats including a trivalent, bispecific Fc fusion protein targeting EGFR, whereby the scDb may be monospecific for EGFR and the scFv (or Fab) for CD3 binding may be alternatively positioned as the scFv of the second polypeptide with the Fc(knob) mutation; with reference to Fig. 6 for an overview of formats (pg. 27, Example 11, para. 0217).
It would have been obvious to one of skill in the art to utilize the anti-EGFR/anti-CD3 construct of Kontermann as the TSB antibody domain of the first polypeptide construct of app ‘938. One would have been motivated to do so given that the anti-EGFR/anti-CD3 antibody targets the tumor associated antigen EGFR for the purpose of targeting the construct to the tumor or tumor microenvironment, as taught by Kontermann, where the NBD would bind (and dimerize around) the excessive ATP in the tumor microenvironment, as taught by app ‘938. There would have been a reasonable expectation for success given that app ‘938 teaches that the polypeptide comprising the NBD may also comprise the TSB amino acid sequence of an EGFR antibody, and that Kontermann teaches the anti-EGFR/anti-CD3 antibody construct successfully targets EGFR-expressing tumor cells. Thus, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made.
The combination construct of app ‘938 and Kontermann would comprise a first polypeptide comprising a Fc (knob) and the NBD of app ‘938 linked, directly or via a linker, to the C-terminal or N-terminal of the Fc (knob), and a second polypeptide comprising an Fc (hole) and an anti-EGFR/anti-CD3 bispecific scDb at the N-terminus, whereby the Fc domains form a heterodimer IgFc as a single construct. The construct comprising two polypeptides includes the interspecific amino acid sequence pair of knob-in-hole (KiH) sequences (re. claims 2-3). The construct may also include a 4-1BBL, as taught by Kontermann (pg. 18, para. 0121), which is a therapeutic agent (re. claim 4). The construct comprises an additional anti-EGFR scFv on the first polypeptide chain (re. claim 6).
Thus, the construct of the combination of app ‘938, claim 1, and Kontermann makes obvious the construct of instant claim 1, comprising an NBD of SEQ ID NO: 16 and two heavy chain constant regions comprising an Fc; wherein the Fc have KiH mutations of instant claims 2-3; wherein the construct comprises a therapeutic agent of instant claim 4; wherein the construct comprises an EGFR TSB of instant claims 5 and 7, which is an scFv of instant claim 6; whereby the construct comprises an NBD that can homodimerize and which comprises an anti-CD3 ICB of instant claim 8, whereby only one polypeptide comprises the NBD and the second polypeptide comprises the ICB of claim 9, with KiH mutations of instant claims 10 and 12, with a 4-1BBL therapeutic agent of claim 11, wherein the ICB targets CD3 of claims 13-14. The construct comprising the NBD, when bound to ATP, makes obvious the bound complex of instant claim 16. Kontermann teaches the construct may be formulated in a pharmaceutical composition comprising a pharmaceutically acceptable carrier, and thus makes obvious instant claims 17 and 22.
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