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 .
Application Status
The amended claims filed October 22, 2025 are acknowledged. Claims 1-4, 7-8, 11, 16, 21-22, 25-28, 32-35, 37-38, 40, 104, 107-109, 111-112, 114, 118, 122, 125-126, 131, 135, 149-152, and 165 are pending. Claims 4, 8, 34-35, 109, and 112 have been amended. Claims 8, 11, 32, 37-38, 40, 112, 114, and 131 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-4, 7, 16, 21-22, 25-28, 33-35, 104, 107-109, 111, 118, 122, 125-126, 135, 149-152, and 165 are under examination herein.
It is noted that although the Remarks filed with the Response to the non-final Office Action on October 22, 2025 state that claim 3 has been canceled (e.g., page 21), the claim still appears in the claim set filed with said Response and is denoted as “previously presented”. It is further noted that claims 4, 7-8, and 11 depend directly or indirectly from claim 3.
Objections to the Specification Withdrawn
The objection to the specification is withdrawn in view of Applicant's amendments to the specification renumbering the tables in numerical order in order of appearance and updating in-text citations as appropriate.
Claim Rejections Withdrawn
The rejection of claims 34-35 under 35 U.S.C. 112(a) as failing to comply with the written description requirement is withdrawn in view of Applicant’s amendments thereto.
MAINTAINED REJECTIONS
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 3-4 and 109 are 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 claims contain 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a maintained rejection that has been updated in response to Applicant’s claim amendments.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the 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. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP § 2163.04.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or it may be satisfied by the disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. “Functional” terminology may be used “when the art has established a correlation between structure and function” but “merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing one has invented a genus and not just a species. Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 598 F3d 1336, 94 USPQ2d 1161, 1171 (Fed Cir. 2010).
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). “[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention. For example, the Federal Circuit has found that possession of a mouse antibody heavy and light chain variable regions provides a structural "stepping stone" to the corresponding chimeric antibody, but not to human antibodies. Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875 (Fed. Cir. 2011).
The claimed invention. The nature and scope of the claimed invention at issue is an Fc polypeptide dimer-antibody variable region fusion protein comprising an antibody variable region that is capable of binding human epidermal growth factor receptor 2 (HER2) or an antigen-binding fragment thereof, wherein the antibody variable region binds to subdomain IV of human HER2 and comprises one or more complementarity determining regions (CDRs) selected from the group consisting of (a) a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 69, (b) a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 70, (c) a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 71, (d) a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 72, (e) a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 73, and (f) a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 74, as recited in claims 3-4. Claim 3 recites that the antibody binds to a specific epitope (subdomain IV, II, or I) of human HER2 without reciting a corresponding structure expected to correlate with this specific function. Claim 4 would permit a significant level of sequence variation for the claimed heavy chain and light chain CDRs, such that as few as one CDR from the group of six may be selected. Such variation in the amino acid structure would be expected to significantly impact the specificity of the antibody variable region for the recited epitope of the target antigen.
Similarly, claim 109 discloses an antibody heavy chain comprising an antibody heavy chain variable region comprising one or more CDRs selected from the group consisting of (a) a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 69, (b) a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 70, and (c) a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 71. The claim would permit a significant level of sequence variation for the claimed heavy chain CDRs, such that as few as one CDR from the group of three may be selected. Such variation in the amino acid structure would be expected to significantly impact the antigen binding properties of the protein.
State of the prior art. Schroeder and Cavacini (Journal of Allergy and Clinical Immunology (2010) 125(2, Suppl.2): S41-S52; cited in PTO-892 mailed August 8, 2024) teach that conventional immunoglobulins (antibodies) known in the art are composed of two heavy and two light chains. These chains can be separated functionally into variable domains, which are responsible for antigen binding, and constant domains, which specify effector functions (Abstract). The variable domains are produced by complex genetic recombination and affinity maturation events. Each variable domain (heavy and light) can be split into three regions of sequence variability (i.e., CDRs). The six heavy and light chain CDRs are paired to form the antigen-binding site as classically defined (Abstract). It is understood in the art that, for a conventional antibody or immunoglobulin, the structural element that correlates with its function is these six CDRs. As discussed by Sela-Culang et al. (Frontiers in Immunology (2013) 4: 302; cited in PTO-892 mailed August 8, 2024), “A major focus in analyzing the structural basis for [antigen] recognition has been in identifying the exact boundaries of the CDRs in a given [antibody]. It is a common practice to identify paratopes through the identification of CDRs” (page 3, left column, “CDRs Identification”). Although the prior art teaches some understanding of the structural basis of antigen-antibody recognition, it is aptly noted that the art is characterized by a high level of unpredictability, since the skilled artisan still cannot accurately and reliably predict the consequences of amino acid substitutions, insertions, and deletions in the antigen-binding domains. Ni (The Protein Journal (2024) 43: 683-696) teaches, “Mutations, even one mutation, introduced in the CDRs through [somatic hypermutation] can change the binding properties and repertoire of antibodies. However, how just one-point mutation can dramatically change the recognition profiles of the antibody is still unclear” (Introduction). Furthermore, while affinity maturation techniques can result in differences in the CDRs of the antibody compared to its parental antibody, those techniques involve trial-and-error testing and the changes that maintain or improve affinity are not predictable a priori (pages 3 and 6-7; Almagro, Frontiers in Immunology (2018) 8:1751).
Gershoni (Biodrugs (2007) 21(3): 145-156) teaches that antibody binding to the same antigen, or even the same epitope on that antigen, can be accomplished with an impressively wide variety of antibody structures, even when the antibodies are limited to those from a particular source (page 146, Section 1.1). The skilled artisan therefore understands that antibodies from a variety of different sources may bind the same antigen and even mediate the same functional effects, but differ widely in the details of the structure of their antigen-binding sites, particularly in the amino acid sequence. With respect to HER2, Yu et al. (Experimental Hematology & Oncology (2017) 6: 31; cited in PTO-892 mailed August 8, 2024) teach that there are several therapeutic anti-HER2 antibodies known in the prior art, including trastuzumab (which binds domain IV of HER2), pertuzumab (which binds domain II of HER2), and ertumaxomab (which simultaneously targets HER2 on tumor cells and CD3 on T cells while activating accessory cells via its Fc fragment to promote antibody-dependent cellular cytotoxicity) (Abstract; Introduction).
Scope of species disclosed in original specification. The working examples disclose Fc polypeptide dimer-antibody variable fusion proteins wherein HER2 binding sites were engineered into the Fab arms of a TfR-binding polypeptide, including anti-HER2_DIV (comprising heavy and light chains comprising the amino acid sequences of SEQ ID NO: 97 and 57, respectively) and anti-HER2_DII (comprising heavy and light chains comprising the amino acid sequences of SEQ ID NO: 98 and 58, respectively) (¶ 0448). The first Fc polypeptide “CH3C.35.23.1.1” comprises a TfR binding site and the second Fc polypeptide does not have a TfR-binding site or any modifications that reduce FcɣR binding (¶ 0449). Different permutations of the fusion protein in which the first Fc polypeptide comprises a LALA mutation or a LALA mutation and knob mutation were tested in the resulting “ATV” molecules (Tables 1-2, pages 116-117). The working examples further disclose the Fc polypeptide construct “CH3C.35.23.4”, which in some iterations also comprised a LALA mutation (“cisLALA”) or a LALA mutation in combination with a knob mutation and was integrated into fusion proteins comprising anti-HER2_DII or anti-HER2_DIV, fused to antibody variable domains comprising both the heavy and light chains of the anti-HER2_DII and anti-HER2_DIV antibodies or to anti- heavy chain Fd (VH+CH1) portions of the anti-HER2_DII and anti-HER2_DIV antibodies (Examples 8-9; Tables 7-8, pages 123-124).
MPEP § 2163 states that a “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. As recited in the disclosure, the ATV fusion proteins comprising an anti-HER2 subdomain IV antibody or antigen-binding fragment thereof comprise a single, distinct combination of three heavy chain CDRs (instant SEQ ID NO: 69-71, respectively) and three light chain CDRs (SEQ ID NO: 72-74, respectively), without any sequence variation. The ATV fusion protein comprising an anti-HER2 subdomain II antibody or antigen-binding fragment thereof comprising a single, distinct combination of three heavy chain CDRs (SEQ ID NO: 75-77, respectively) and three light chain CDRs (SEQ ID NO: 78-80, respectively), without any sequence variation. The disclosure of a single embodiment comprising all six CDRs, with 100% sequence identity to the instantly claimed CDR sequences, cannot be said to be fully representative of the broad genus of possible anti-HER2 antibody variable regions that bind to HER2 subdomains IV or II.
In the absence of a representative number of species, the written description requirement for a claimed genus may be satisfied by disclosure of relevant, identifying characteristics; i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. It is unclear from the disclosure which residue(s) could be mutated in the claimed CDRs, or which CDRs could be eliminated completely (reading on the limitation that the claimed fusion protein comprises “one or more” CDRs from the selected groups), without comprising the anti-HER2 binding properties of the resultant polypeptide.
Conclusion. For all of the reasons presented above, one of skill in the art would not know which of the countless fusion proteins encompassed by the highly general structural requirements of the claims would also possess the required functional activity of binding to subdomain IV of HER2. Therefore, the skilled artisan would not reasonably conclude that the inventors had full possession of antibodies as broadly claimed at the time the application was filed. Given the lack of shared structural properties that provide the claimed binding activity, the limited number of species described, and the fact that the species that were described cannot be considered representative of the broad genus, Applicant was not in possession of the invention as claimed.
Response to Arguments
Applicant's arguments filed October 22, 2025 have been fully considered but they are not persuasive.
Applicant submits that “the rejection is moot in view of the cancelation of claim 3 and the amendments to claims 4, 34, 35, and 109.” Remarks at page 22.
In response, it is noted that claim 3 is not canceled in the claims filed October 22, 2025. In addition, the scope of the instantly claimed antibody variable regions remains such that as little as one of the six total CDRs in a complete antigen-binding region may be structurally defined, as set forth with the “one or more [CDRs] selected from the group consisting of” language in the claims. This is much broader in scope than the instant disclosure, which recites fusion protein constructs comprising an antibody variable region having a defined set of three heavy chain and three light chain CDRs. Examples of constructs comprising fewer than six fully defined CDR sequences for an antibody variable domain specifically binding subdomain IV of HER2 are not provided in the instant disclosure. The state of the art recognizes that for a conventional antibody, all six CDRs (three in the heavy chain and three in the light chain) are required for functional binding to a given epitope of an antigen.
MPEP § 2163 (II)(A)(3)(a)(ii) states in relevant part: “("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed."
For these reasons, the rejection is maintained.
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 1-4, 7, 16, 21-22, 25-28, 33-35, 104, 107-109, 111, 118, 122, 125-126, 135, 149-152, and 165 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 10-12, 14-15, 17-19, 25, 27, 29, 40-45, 47-49, 53, 140, 144, 149, and 153 of co-pending Application No. 17/819,182 (reference application; cited in PTO-892 mailed April 28, 2025). This is a maintained rejection.
Regarding instant claims 1-3, 21-22, 25-28, and 33, co-pending claims 1-2 recite a protein comprising an Fc dimer and an antibody variable region (Fab or scFv) that binds to subdomain IV of HER2. Co-pending claim 10 recites that the first Fc polypeptide specifically binds to a transferrin receptor. Co-pending claims 17-19 recite that the first Fc polypeptide comprises a sequence having at least 90% identity to SEQ ID NO: 137 (which shares 100% identity to the instant first Fc polypeptide comprising instant SEQ ID NO: 124) and comprises Tyr at position 384, Thr at position 386, Glu at position 387, Trp at position 388, Ser at position 389, Ser at position 413, Glu at position 415, Glu at position 416, and Phe at position 421, according to EU numbering; and the second Fc polypeptide comprises SEQ ID NO: 133 (which shares 100% identity to the instantly claimed second Fc polypeptide that comprises instant SEQ ID NO: 67 and does not have modifications that create a TfR binding site). Co-pending claim 19 further recites that the first Fc polypeptide comprises Ala at position 234, Ala at position 235, and Trp (W) at position 366, and that the second Fc polypeptide comprises Ser at position 366, Ala at position 368, and Val at position 407. Since products of identical composition cannot have mutually exclusive properties (see MPEP § 2112.01), the co-pending protein would be expected to also have the properties recited in instant claims 16 and 104. Co-pending claims 25, 27, 29, 40-45, and 47-49 recite similar limitations. The co-pending claims also anticipate the instantly claimed antibody heavy chain recited in instant claims 107-108, 118, 122, 125-126, and 165.
Regarding instant claims 4, 7, 34-35, 109, 111, and 135, co-pending claim 53 recites that the protein comprises the sequences of:
SEQ ID NO: 33 (for which residues 1-120 share 100% identity to the instantly claimed heavy chain variable domain comprising SEQ ID NO: 59, with its corresponding CDRs comprising SEQ ID NO: 69-71, and residues 1-450 share 100% similarity to the instantly claimed first heavy chain comprising instant SEQ ID NO: 18),
SEQ ID NO: 38 (for which residues 1-449 share 100% similarity to the instantly claimed second heavy chain comprising SEQ ID NO: 27), and
SEQ ID NO: 26 (for which residues 1-107 comprise 100% identity to the instantly claimed light chain variable domain comprising SEQ ID NO: 60, with its corresponding CDRs comprising SEQ ID NO: 72-74, and 100% identity to the instantly claimed light chain comprising SEQ ID NO: 57).
Regarding instant claim 149, co-pending claims 140 and 149 pharmaceutical compositions comprising a protein of co-pending claims 1 or 25, respectively. Regarding instant claims 150-152, co-pending claims 144 and 153 recites administering a therapeutically effective amount of the proteins of co-pending claims 1 or 25, respectively. The instantly claimed limitations are obvious variations that could be applied to the co-pending fusion proteins sharing complete structural similarity to the instantly claimed Fc polypeptide dimer-antibody variable region fusion protein, to create patentably indistinct variations of the same invention. See MPEP § 804.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed October 22, 2025 have been fully considered but they are not persuasive.
Applicant states that when a provisional non-statutory double patenting rejection is the only rejection remaining in a utility application having an earlier patent term filing date, the rejection should be withdrawn.
In response, it is noted that the provisional non-statutory double patenting rejection is not the only rejection remaining in the instant application. Accordingly, the rejection is maintained.
Claims 1-4, 7, 16, 21-22, 25-28, 33-35, 104, 107-109, 111, 118, 122, 125-126, 135, 149-152, and 165 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 14, 27, 31, 35, 49, 62, 66 of co-pending Application No. 18/685,583 (reference application; cited in PTO-892 mailed April 28, 2025). Although the claims at issue are not identical, they are not patentably distinct from each other because the co-pending claims anticipate the instantly claimed invention. This is a maintained rejection.
Regarding instant claims 1-3, 25-26 and 28, the co-pending reference application recites a protein comprising first and second Fc polypeptides that form an Fc dimer and a Fab that binds to subdomain IV of HER2, wherein the first Fc polypeptide specifically binds to a TfR and wherein the first and/or second Fc polypeptides comprise modifications that promote heterodimerization (co-pending claims 1 and 14). Co-pending claim 27 recites that the first Fc polypeptide comprises SEQ ID NO: 137, which shares 100% identity to the instantly claimed modified Fc polypeptide comprising instant SEQ ID NO: 124 and having the 11 modifications recited in instant claim 1.
Regarding instant claims 21-22, 25-28, and 33¸ co-pending claim 31 recites that the first Fc polypeptide comprises Ala at position 234, Ala at position 235, Trp at position 366, and an amino acid sequence of SEQ ID NO: 137 (which comprises 100% identity to instant SEQ ID NO: 124 as recited above) and a second Fc polypeptide comprising Ser at position 366, Ala at position 368, and Val at position 407, and an amino acid sequence of SEQ ID NO: 133, which shares 100% identity with instant SEQ ID NO: 67. Co-pending claims 35, 49, 62, and 66 recite similar subject matter. Regarding instant claims 16 and 104, the protein recited in the co-pending claims would be expected to possess the same properties since products of identical composition cannot have mutually exclusive properties. See MPEP § 2112.01.
The co-pending claims also anticipate the instantly claimed antibody heavy chain recited in instant claims 107-108, 118, 122, 125-126, and 165.Relevant to instant claims 4, 7, 34-35, 109, 111, and 135, co-pending claim 68 recites a protein comprising a first heavy chain comprising the amino acid sequence of SEQ ID NO: 6 (which shares 100% sequence identity to the instantly claimed first heavy chain comprising SEQ ID NO: 18), a second heavy chain comprising the amino acid sequence of SEQ ID NO: 160 (for which residues 1-450 share 100% similarity to the instantly claimed second heavy chain comprising SEQ ID NO: 27), and two light chains comprising the amino acid sequence of SEQ ID NO: 26 (which shares 100% sequence identity to the instantly claimed light chains comprising SEQ ID NO: 57). The recited anti-HER2 binding protein comprises an obvious variant of the antigen-binding domain co-pending fusion protein that binds to subdomain IV of HER2, and could be applied to the co-pending proteins sharing complete structural similarity to the instantly claimed Fc polypeptide dimer-antibody variable region fusion protein, to create patentably indistinct variations of the same invention. See MPEP § 804.
Regarding instant claims 149-152, co-pending claims 70 and 74 recites a pharmaceutical composition and a method of treatment that comprises administering a therapeutically effective amount of the protein of co-pending claim 1. The instantly claimed limitations are obvious variations that could be applied to the co-pending proteins sharing complete structural similarity to the instantly claimed Fc polypeptide dimer-antibody variable region fusion protein, to create patentably indistinct variations of the same invention. See MPEP § 804.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed October 22, 2025 have been fully considered but they are not persuasive.
Applicant states that when a provisional non-statutory double patenting rejection is the only rejection remaining in a utility application having an earlier patent term filing date, the rejection should be withdrawn.
In response, it is noted that the provisional non-statutory double patenting rejection is not the only rejection remaining in the instant application. Accordingly, the rejection is maintained.
Claims 1-4, 16, 21-22, 25-28, 33-34, 104, 107-109, 111, 118, 122, 125-126, 135, and 165 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 34-41, 43-45, and 54-56 of co-pending Application No. 18/685,587 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the co-pending claims anticipate the instantly claimed invention. This is a maintained rejection.
Regarding instant claims 1-3, 16, 21-22, 25, 28, 33, 107-108, 118, 122, 125, and 165, the co-pending reference application recites an isolated antibody comprising a first antigen-binding site that binds to subdomain IV of HER2 and a modified Fc polypeptide dimer comprising a first Fc polypeptide and a second Fc polypeptide, wherein the first Fc dimer polypeptides identical modifications in the CH3 that create a TfR binding site relative to that instantly claimed (i.e., co-pending claims 34-39) and the Fc polypeptides further comprise identical modifications that promote heterodimerization (i.e., co-pending claims 40-41) and reduce TfR-mediated effector function (i.e., co-pending claims 43-45). Such an antibody, having the same structural properties as instantly claimed, would be expected to have the properties recited in instant claim 104.
Regarding instant claim 26 and 126, co-pending claim 54 recites that the first Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 86, which shares 100% identity to instant SEQ ID NO: 124. Regarding instant claim 27, co-pending claim recites that the second Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 85, which shares 100% identity to instant SEQ ID NO: 67.
Regarding instant claims 4, 34, 109, 111, and 135, co-pending claim 55-56 recites the isolated antibody of co-pending claim 34, comprising a first antigen binding site comprising the amino acid sequence of SEQ ID NO: 15 (which shares 100% identity to the instantly claimed first heavy chain comprising instant SEQ ID NO: 18, and residues 1-120 share 100% similarity to instant SEQ ID NO: 59), and first and second Fc polypeptides comprising SEQ ID NO: 86 and 85, respectively. The instantly claimed limitations are obvious variations that could be applied to the co-pending proteins sharing complete structural similarity to the instantly claimed Fc polypeptide dimer-antibody variable region fusion protein, to create patentably indistinct variations of the same invention. See MPEP § 804.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed October 22, 2025 have been fully considered but they are not persuasive.
Applicant states that when a provisional non-statutory double patenting rejection is the only rejection remaining in a utility application having an earlier patent term filing date, the rejection should be withdrawn.
In response, it is noted that the provisional non-statutory double patenting rejection is not the only rejection remaining in the instant application. Accordingly, the rejection is maintained.
Conclusion
No claims are allowed.
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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/ELIZABETH A SHUPE/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643