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 claims benefit under 35 U.S.C. 119(e) to U.S. Provisional application 62/313,213, filed 2/23/2022.
Election/Restrictions
Applicant’s election without traverse of Group I, encompassing claims 1, 3-9, 13-19, and 53-55, in the reply filed on 1/23/2026 is acknowledged. Applicants subsequently canceled claims 1, 3-9, 13-20, 45 and 53-55; amended claim 19; and added new claims 56-71, in the remarks of 1/23/2026. Applicant’s election of species of anti-HER2 sdABD with the set of CDRs of SEQ ID NOs: 504-506 is acknowledged. Election was made without traverse in the reply filed on 1/23/2026.
Status of Claims
Claims 19 and 56-71 are pending and are being examined on the merits.
Claim Objections
Claim 66 is objected to because of the following informalities: the second line of claim 66, recites “sequence selected from group consisting of…”. The sentence is missing an identifier before “the” group consisting of. Appropriate correction is required.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 66 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 66 recites the fusion protein of claim 56 wherein the fusion protein has an amino acid sequence selected from a group consisting of SEQ ID NOs: 459-484 and 491-494. Said SEQ ID NOs correspond to the total amino acid sequence of the fusion protein across varying embodiments. Claim 56 depends from claim 19 which recites the amino acid sequence of the sdABD HER2, which may be either the full length sdABD of SEQ ID NO: 503, or comprise the CDRs 1-3 of SEQ ID NOs: 504-506. Applicants amended claim 19, canceling reference to alternative species of the HER2 sdABD, such that only a single embodiment of the HER2 sdABD is claimed, wherein it comprises the CDRs 1-3 of SEQ ID NOs: 504-506. Of the group consisting of SEQ ID NOs: 459-484 and 491-494, of claim 66, only SEQ ID NOs: 478 and 494 comprise the required CDRs 1-3 of SEQ ID NOs: 504-506. That is, for example, the fusion protein of SEQ ID NO: 459 does not comprise the CDRs of SEQ ID NOs: 504-506, and thus fails to include all the limitations of the claim from which it depends. Thus, claim 66 is rejected for failing to include all the limitations of the claim from which it depends. Applicant is advised to amend claim 66 to correspond accordingly to amended claim 19, such that alternative embodiments of the full length fusion proteins which do not comprise the required CDRs of SEQ ID NOs: 504-506, are removed.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 71 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made, of the specific subject matter claimed. To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
Claim 71 recites a method of treating cancer in a subject by administering a HER2 sdABD. One skilled in the art would readily appreciate that a HER2 sdABD could be used to treat a HER2-expressing cancer; however the claims are drawn to a method of treating any cancer by administering a HER2 sdABD. Absent empirical determination one skilled in the art would be unable to envision which cancers that do not express HER2 could be treated with the claimed HER2 sdABD. Applicant is informed that this written description issue may be overcome by amending the claims to specifically recite a method of treating HER2-expressing cancers/tumors.
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 19 and 56-71 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 53-69 and 72 of copending Application No. 18/021,730 (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 ‘730 anticipate that of the instant claims.
Application ‘730 claims a sdABD that binds human HER2 comprising a set of CDRs 1-3 of SEQ ID NOs: 504-506, respectively (claim 53), or the full length sdABD of SEQ ID NO: 503 (claim 54). App ‘730 SEQ ID NOs 503-506 are 100% identical to instant SEQ ID NOs: 503-506, of instant claim 19. App. ‘730 further claims the sdABD of claim 53 in a fusion protein, whereby the limitations of the fusion protein of app ‘730 dependent claims 55-65 are identical, in every word, to that of instant dependent claims 56-66. App. ‘730 claims nucleic acids, vectors, host cells, methods of making a sdABD and methods of treating cancer in dependent claims 66-69 and 72, which are identical to instant dependent claims 67-71, respectively. Thus, the invention of application ‘730 claims 53-69 and 72 are identical to the invention of instant claims 19 and 56-71.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 19, 56-62, 65 and 67-71 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 47-54, 58 and 61-66 of copending Application No. 18/024,597 (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 ‘597 anticipate that of the instant claims.
Application ‘597 claims a fusion protein comprising a sdABD which binds to a human tumor target antigen (claim 47), wherein the tumor antigen is HER2 (claim 54), wherein the fusion protein has the amino acid sequence of SEQ ID NO: 238 (claim 61). The fusion protein of SEQ ID NO: 238 comprises the anti-HER2 sdABD of instant SEQ ID NO: 503 with 100% sequence identity, including the sdABD CDRs 1-3 of instant SEQ ID NOs: 504-506, respectively, with 100% sequence identity. Thus, the fusion protein of application ‘597 claims 47, 54 and 61 anticipate the fusion protein of instant claims 19 and 56.
Application ‘597 also claims wherein the first and second sdABD-HER2 are the same (claim 52), or different (claim 53); whereby the fusion protein is in various formats (claims 48-51); whereby the cleavable linker is MMP2 (claim 58). Application ‘597 also claims nucleic acids encoding the fusion protein (claim 62), vectors comprising the nucleic acids (claim 63), host cells comprising the vector (claim 64), methods of making the fusion protein (claim 65) and methods of treating cancer (claim 66). Thus, application ‘597 anticipates instant claims 57-62, 65 and 67-71.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 19, 56-63, 65 and 67-71 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4, 6, 8, 14, 18, 20, 26, 28, 34 and 39 of copending Application No. 18/266,848 in view of May et al. (from IDS; WO 2019/051102; published 3/14/2019; henceforth WO '102).
Application ‘848 claims a protein (claim 1) comprising from N- to C- terminus:
A first sdABD-TTA,
A first domain linker
A constrained scFv, including a constrained non-cleavable linker (CNCL)
A first cleavable linker
A second sdABD-TTA
A second domain linker
A second constrained scFv, including a second CNCL
A second cleavable linker
A third sdABD-HSA that binds to human serum albumin (HSA);
wherein the first and/or second sdABD targets HER2 (claim 14), wherein the anti-HER2 sdABD has the amino acid sequence of SEQ ID NO: 95 (claims 26 and 28).
The anti-HER2 sdABD of Application ‘848 SEQ ID NO: 95 comprises the CDRs 1-3 of instant SEQ ID NOs: 504-506 (of instant claim 19), respectively, with 100% amino acid sequence identity.
The difference is that construct of application ‘848 has a cleavable linker at position (iv or d) and a second domain linker at position (vi or f); whereas the instant fusion protein has a second domain linker at position (iv or d) and a cleavable linker at position (vi or f).
WO ‘102 teaches constrained conditionally activated binding proteins, whereby upon exposure to tumor proteases, the constructs are cleaved and activated such that they can bind both tumor target antigens as well as CD3, thus recruiting T cells expressing CD3 to the tumor, resulting in treatment (abstract). WO ‘102 teaches the present invention provides a number of different protein compositions; including “Format 2” (pg. 2, para. 0005), in which the construct has a non-cleavable linker (i.e. second domain linker) at position (iv or d) and a cleavable linker at position (vi or f). Alternatively, WO ‘102 teaches “Format 4” (pg. 3, para. 2), in which the construct has a cleavable linker at position (iv or d) and a second domain linker at position (vi or f). Thus, WO ‘102 teaches constrained conditionally activated binding proteins which comprise all the components of the format of the instant fusion protein, and teaches that the cleavable linker between the first constrained Fv and second pseudo Fv domain may be at the linker position of (iv or d) or at the position of (vi or f). WO ‘102 teaches “Figure 4 depicts ‘format 4’ type of constructs that are similar to ‘format 2’ constructs but have only a single sdABD-TTA. The figure shows that the sdABD-TTA to EGFR but as will be appreciated by those in the art, other TTA can be used as well. Upon cleavage, the prodrug construct splits into two components, a half-life extension domain linked to a pseudo Fv and an active moiety, that in the presence of a second active moiety from a different cleaved molecule, self-assembles into a dimeric active moiety that contains two anti-TTA domain”, (pg. 8, para. 0027).
It would have been obvious to one of skill in the art to switch the position of the cleavable linker separating the first Fv and the second pseudo Fv such that the second sdABD-TTA stays connected with the first Fv instead of the pseudo Fv after cleavage by the proteosome. One would have been motivated to do so have a first Fv with two sdABD-TTA binding domains and to remove the sdABD-TTA biding domain from the half-life sdABD-HSA linked pseudo Fv domain after cleavage; thus resulting in an active moiety with two anti-TTA domains. There would have been a reasonable expectation for success given that the constrained conditionally activated binding proteins can be formatted to split into a different secondary constructs, depending on where the cleavable linker is inserted, as taught by format 2 and format 4 constructs, which were reduced to practice, as taught by WO ‘102. Thus, the invention was prima facie obvious to one of skill in the art at the time the invention was made.
The protein of application ‘848, claim 1, comprising an anti-HER2 sdABD-TTA, of claims 26 and 28, in the modified format of WO ‘102, make obvious the fusion protein of instant claims 19 and 56.
Application ‘848 also claims wherein the first immune cell is a T cell (claim 2), wherein the first immune antigen is CD3 (claims 4, 6 and 34); whereby the first VH may be linked to the N- or C-terminus of the first VL (claim 8), whereby the cleavable linker is cleaved by a protease in a tumor microenvironment (claim 18), which may be MMP2 (claim 20). Application ‘848 claims wherein the third sdABD (i.e. the sdABD-HSA) comprises SEQ ID NO: 220 (claim 38); application ‘848 SEQ ID NO: 220 is 100% identical to the HSA sdABD of instant SEQ ID NO: 245 of instant claim 63. Application ‘848 claims wherein the protein comprises the amino acid sequence of SEQ ID NO: 244 (claim 39); SEQ ID NO: 244 comprises instant SEQ ID NO: 503 with 100% sequence identity.
Thus, the combination protein of application ‘848 in the format of WO ‘102, claims 26-28 make obvious instant claims 57-58; app ‘848 claim 8 makes obvious instant claims 59-62; app ‘848 claim 38 makes obvious instant claim 63; app ‘848 claim 20 makes obvious instant claim 65. Further, WO ‘102 teaches nucleic acids, vectors and host cells, methods of making the protein and methods of treating cancer comprising administering the protein (pg. 62, claims 14-18), and thus the combination of application ‘848 and WO ‘102 make obvious instant claims 67-71. This is a provisional nonstatutory double patenting rejection.
Allowable Subject Matter
An anti-HER2 sdABD comprising SEQ ID NO: 503, or the CDRs 1-3 of SEQ ID NOs: 504-506, respectively, has been searched and would be free of the art pending resolution of the double patenting rejections as recited above.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAMES R. MELCHIOR whose telephone number is (703)756-4761. The examiner can normally be reached M-F 8:00-5:00 CST.
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/JAMES RYLAND MELCHIOR/Examiner, Art Unit 1644
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642