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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on June 2, 2026 has been entered.
Application Status
The amended claims filed June 2, 2026 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, 109, and 112 have been amended. Claim 3 is newly canceled. Claims 8, 11, 32, 37-38, 40, 112, 114, and 131 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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.
CLAIM REJECTIONS WITHDRAWN
All prior grounds of rejection over claim 3 are rendered moot by the cancelation of the claim.
The rejection of claims 4 and 109 under 35 U.S.C. 112(a) as failing to comply with the written description requirement is withdrawn in view of Applicant’s amendments to the claims.
MAINTAINED REJECTIONS AND NEW OBJECTIONS AND REJECTIONS
Claim Objections
Claims 34-35 are objected to because of the following informalities:
Claim 34 (in line 4) should recite “SEQ ID NO:” instead of “SEO ID NO:”.
Claim 35 (in line 3) should recite “SEQ ID NO:” instead of “SEO ID NO:”. In addition, it is noted that claim 35 recites that the first heavy chain comprises the amino acid sequence of SEQ ID NO: 59 (which corresponds to a VH sequence; see Informal Sequence Listing in specification) while the second heavy chain comprises the amino acid sequence of SEQ ID NO: 27 (which corresponds to a full heavy chain sequence; see Informal Sequence Listing in specification). It is unclear if this is intended by Applicant.
Appropriate correction is required.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claims 1-2, 4, 7, 16, 21-22, 25-28, 33-35, 104, 107-109, 111, 118, 125-126, 135, 149-152, and 165 are rejected under 35 U.S.C. 103 as being obvious over Chen (US 2018/0237496 A1; filed March 23, 2018; earliest priority date: November 8, 2017; cited in IDS) in view of Klein (WO 2016/207091 A1; cited in IDS).
The applied reference of Chen has a common applicant (Denali Therapeutics, Inc.) with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
Chen discloses polypeptides that are capable of being actively transported across the blood-brain barrier (BBB), comprising (i) an antibody variable region sequence that is capable of binding an antigen, or an antigen-binding fragment thereof, comprising a Fab domain, and (ii) a modified Fc polypeptide dimer that comprises a site that specifically binds to a BBB receptor, e.g., wherein the modified Fc polypeptide dimer comprising a first Fc polypeptide with a modified CH3 domain sequence that can bind to a transferrin receptor (TfR), which can be derived from human IgG1, IgG2, IgG3, or IgG4, and a second Fc polypeptide that does not comprise a site that binds to a TfR (e.g., ¶ 0029-0041). In an exemplary embodiment, Chen discloses an Fc polypeptide clone “CH3C.35.23.4” which shares 100% sequence identity to instant SEQ ID NO: 124 (including the TfR-binding mutations thereof1) and further comprises a knob mutation corresponding to T366W and LALA mutations corresponding to L234A and L235A (e.g., Table at page 81; ¶ 0280-0288), relevant to claims 1-2, 16, 21-22, 25-26, 28, 33, 104, 107-108, 118, 122, 125-126, and 165.
Regarding claims 1 and 25-26, Chen teaches an exemplary CH3-modified clone “CH3C.35.23.4” comprising the amino acid sequence of SEQ ID NO: 386, which shares 100% sequence identity to the first Fc polypeptide comprising the amino acid sequence of instant SEQ ID NO: 124.
Regarding claims 25 and 27-28, by adding the modifications set forth in ¶ 0235 of Chen in the second Fc polypeptide (where the mutations are recited relative to SEQ ID NO: 1, corresponding to the human Fc sequence as set forth on pages 54-55), one would arrive at an amino acid sequence of instant SEQ ID NO: 67, wherein the Fc polypeptide comprises the hole mutations of T366S, L368A, and Y407V according to EU numbering (e.g., ¶ 0232-0237; Informal Sequence Listing at pages 54-55).
Chen further provides for pharmaceutical compositions comprising the BBB receptor-binding polypeptides of the invention (e.g., ¶ 0374-0383), relevant to claim 149. Relevant to claims 150-152, Chen recites that BBB receptor-binding polypeptides of the invention can be administered in methods of treatment (e.g., primary or metastatic cancer of the central nervous system) and/or to transport a therapeutic moiety across the BBB (e.g., ¶ 0367-0373).
However, Chen does not expressly recite that the Fc polypeptide dimer-antibody variable region fusion proteins of the invention comprise an antibody variable region that binds to HER2.
Klein discloses trispecific antibodies binding to HER2 and a blood-brain barrier (BBB) receptor (BBB-R), pharmaceutical compositions containing said antibodies, and uses thereof (e.g., Abstract). The two binding moieties for HER2 comprise identical light chains based on a consensus of the parental trastuzumab and pertuzumab light chains and the corresponding pertuzumab heavy chain has been remodeled (e.g., page 4, lines 1-4). Regarding claims 1-2 and 28, Klein recites a trispecific antibody comprising a first monovalent Fab that binds to extracellular domain II of HER2, a second monovalent Fab that specifically binds to extracellular domain IV of HER2, and a third monovalent antigen-binding site specific for transferrin receptor (TfR) (e.g., page 4, line 20 to page 5, line 3; claims 1-3). In an embodiment, the TfR antigen-binding site comprises a single chain Fab fragment that is connected directly or by a linker to the C-terminal end of the Fc part of one of the heavy chains of the IgG antibody (e.g., page 40, lines 8-12), wherein the CH3 domain (C-terminal end) of the trispecific antibody Fc comprises a modification that creates a TfR-binding site.
Relevant to claims 4 and 109, the Fab that binds extracellular domain IV of HER2 comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 20 (which shares 100% identity to instant SEQ ID NO: 69; see page 156), a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 29 (which shares 100% identity to instant SEQ ID NO: 70; see page 157), a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 80 (which comprises one amino acid substitution relative to instant SEQ ID NO: 71; see page 157), a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 104 (which comprises one amino acid substitution relative to instant SEQ ID NO: 72; see page 155), a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 18 (which shares 100% identity to instant SEQ ID NO: 73; see page 155), and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 19 (which shares 100% identity to instant SEQ ID NO: 74; see page 155) (claim 10). Relevant to claims 7 and 111, Klein further teaches that the anti-HER2 domain IV variable domains comprise the variable domain amino acid sequences set forth in SEQ ID NOs: 92 and 82, respectively (which share 100% sequence identity to instant SEQ ID NOs: 59 and 60, respectively), corresponding to the trastuzumab heavy chain variable region (VH) and light chain variable region (VL) (e.g., pages 126-127, bridging paragraph).
Klein further teaches the trastuzumab light chain sequence comprising the amino acid sequence of SEQ ID NO: 123 (which shares 100% sequence identity to instant SEQ ID NO: 57) (e.g., Table 1a at pages 91-92), relevant to claims 34-35. Klein also teaches the trastuzumab heavy chain sequence comprising the amino acid sequence of SEQ ID NO: 128 (e.g., Table 1a at page 92), which corresponds to (i) the heavy chain amino acid sequence of instant SEQ ID NO: 18 absent the LALA mutations (at positions 234 and 235 according to EU numbering), the knob mutation (at position 366 according to EU numbering), and the corresponding TfR-binding mutations in the CH3 as set forth above, and (ii) the heavy chain amino acid sequence of instant SEQ ID NO: 27 absent the three hole mutations (T366S, L368A, and Y407V). By incorporating these respective mutations based on the teachings of Chen, the result would be a first anti-HER2 heavy chains comprising 100% sequence identity to instant SEQ ID NO: 18 (relevant to claims 34 and 135), comprising a VH corresponding to instant SEQ ID NO: 59, and a second heavy chain comprising 100% sequence identity to instant SEQ ID NO: 27.
Relevant to claim 16, the Fc domain (comprising a CH3 domain) is a human IgG1 CH3 domain (e.g., page 63, lines 9-10). Regarding claims 21-22, the Fc domain of the trispecific antibody comprises L234A and L235A substitutions. Regarding claim 25, in a particular embodiment, the CH3 domain of the first subunit of the Fc domain comprises a T366W substitution (“knob”), and the CH3 domain of the second subunit of the Fc domain comprises Y407V, T366S, and L368A substitutions (“holes”) to promote heterodimer formation and hinder homodimer formation (e.g., page 56, line 30 to page 57, 22). Because the trispecific antibody comprises the amino acid substitutions favoring Fc heterodimerization and the second Fc subunit does not contain a TfR-binding site, the trispecific antibody would be expected to not substantially deplete reticulocytes, relevant to claim 104.
Regarding claim 149, Klein discloses pharmaceutical compositions comprising a trispecific antibody of the invention (e.g., page 8, lines 4-5).
Regarding claim 152, Klein recites a method comprising the step of administering to an individual an effective amount of the trispecific antibody of the invention to treat cancer, e.g., a HER2+ cancer with brain metastases (e.g., page 82). Regarding claims 150-151, the method of administering the antibody would be expected to comprise contacting the endothelium, as the BBB receptor (transferrin receptor) bound by the third monovalent binding site refers to an extracellular membrane-linked receptor protein expressed on brain endothelial cells which is capable of transporting molecules across the BBB (e.g., page 17, lines 9-21).
Considered together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to modify the antibody-Fc polypeptide dimer construct taught by Chen by substituting an anti-HER2 antibody variable domain such as that described by Klein. The skilled artisan would have been motivated to do so because Klein teaches that the HER2-binding domain would have utility in treating HER2+ cancers, including those that metastasize to the brain. The invention of Chen is drawn in part to the treatment of cancers of the CNS via polypeptide constructs that can transport a therapeutic moiety across the blood-brain barrier. There would have been a reasonable expectation of success because it is within the skill of one of ordinary skill in the art to substitute antibody variable regions in IgG-based constructs, and furthermore, Klein provides a proof-of-concept for an immunoglobulin-based therapeutic moiety that has combined specificity for HER2 and for TfR.
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
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.
(1)
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 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 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 claims 107-108, 118, 122, 125-126, and 165.
Regarding 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 claim 149, co-pending claims 140 and 149 pharmaceutical compositions comprising a protein of co-pending claims 1 or 25, respectively. Regarding 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.
(2)
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 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 claim 1.
Regarding 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 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 claims 107-108, 118, 122, 125-126, and 165. Relevant to 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 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.
(3)
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 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 claim 104.
Regarding claims 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 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 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 for (1), (2), and (3)
Applicant's combined arguments filed June 2, 2026 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. Remarks at page 11.
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 rejections are maintained.
(4)
Claims 1, 16, 21-22, 25, 28, 104, 107-109, 118, 122, 125, 149-152, and 165 are provisionally2 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-14, 16-24 of co-pending Application No. 19/352,786 (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 new rejection.
Regarding claims 1, 16, 21-22, 25, 28, 104, 107-109, 118, 122, 125, and 165, the co-pending reference application claims an isolated antibody (or an anti-HER2 antibody) comprising (i) a first heavy chain comprising three CDRs having the amino acid sequences of SEQ ID NOs: 16-18, respectively (which share 100% sequence identity to instant SEQ ID NOs: 69-71, respectively), and (ii) a first Fc polypeptide that comprises Glu at position 380, Tyr at position 384, Thr at position 386, Glu at position 387, Trp at position 388, Val at position 389, Asn at position 390, Thr at position 413, Glu or Ser at position 415, Glu at position 416, and Phe at position 421, according to EU numbering, and further comprises a T366W substitution; and (iii) a second Fc polypeptide that does not contain a TfR-binding site or any modifications that reduce effector function, and further comprises T366S, L368A, and Y407V substitutions (co-pending claims 1, 4-12, and 14).
Regarding claims 149-152, co-pending claims 16 and 20-22 recite a pharmaceutical composition comprising the anti-HER2 antibody of co-pending claim 14 and a method of treating cancer (e.g., metastatic brain cancer) by administering said antibody.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Elizabeth A Shupe whose telephone number is (703)756-1420. The examiner can normally be reached Monday to Friday, 9:30am - 6:00pm EST.
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/ELIZABETH A SHUPE/Examiner, Art Unit 1643
/Brad Duffy/Primary Examiner, Art Unit 1643
1 The TfR-binding mutations correspond to Glu at position 380, Tyr at position 384, Thr at position 386, Glu at position 387, Trp at position 388, Ser at position 389, Asn at position 390, Ser at position 413, Glu at position 415, Glu at position 416, and Phe at position 421, according to EU numbering, consistent with those set forth in claim 1 of the instant application.
2 A Notice of Allowance has been mailed for the co-pending application.
Prosecution Insights