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 .
DETAILED ACTION
Claims 1-35, 37-38, 40, and 85-181 are pending in the instant application.
Claims 36, 39, and 41-42 were canceled.
Claims 102-181 are new.
Claims 9-28, and 90-101 remain withdrawn.
New claims 113-114, 130-149, 163-164, 170-181 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim.
Thus, claims 9-28, and 90-101, 114, 130-149, 164, 170-181 have been withdrawn.
Claim Status
Applicant previously elected with traverse an anti-HER2 ADC conjugated to a drug-linker of formula I and a PARP inhibitor in combination to a subject with breast cancer. The election requirement was deemed proper and made final for the reasons of record in the Office Action dated 12/4/2024. The Examiner further included a subject with gastric cancer as a species for the method of treatment of an anti-HER2 ADC conjugated to a drug-linker of formula I and a PARP inhibitor in combination.
During the interview on 8/27/2025, the Applicant described convincing data within the application that ovarian cancer has surprising results as further described in the Response to Arguments section below. The Examiner will further include the species of ovarian cancer.
The Examiner will further include lung cancer as a species.
Thus, the species under review are: A) an anti-HER2 ADC conjugated to a drug-linker of formula I and a PARP inhibitor in combination to a subject with: B) breast cancer, gastric cancer, ovarian cancer, or lung cancer.
Claims 1-8, 29-40, 85-89, 102-113, 115-129, 150-163, 165-169 are under examination for the elected species.
Objections and Rejections Withdrawn
The rejections to claims 36, 39, and 41-42 are moot in view of claim cancelation.
The rejection of claims 1-8, 29-35, and 85-89 under 103 are withdrawn in view of claim amendment and surprising results.
The rejection of claims 1-8, 29-35, and 85-89 under Non-statutory Double Patenting is withdrawn in view of claim amendment and surprising results.
Claim Rejections Necessitated by Amendment and Surprising Results
Claim Rejections – 35 USC § 103
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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
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.
Claims 122-129, 150-153, 155-162, 165-169 are rejected under 35 U.S.C. 103 as being unpatentable over US 20160333112 (Naito H et al. reference of record) and further in view of US 20170209594 (Goldenberg DM et al. reference of record).
Regarding claims 122-129, Naito taught an anti-HER2 ADC (abstract), wherein the antibody trastuzumab was conjugated to a linker with the structure:
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(page 99, paragraph 717) and wherein the ADC of example 50 had an average number of 7.8 drug molecules conjugated per antibody (page 100, paragraph 724, example 50). Regarding claim 122, Naito taught the anti-HER2 ADC conjugated to the drug-linker via a thioether bond between the antibody and linker (page 25, paragraph 318). Regarding claim 122, Naito taught the ADC contained an antitumor agent exatecan with the structure of
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, which is a water soluble derivative of camptothecin inhibits topoisomerase to exhibit an antitumor effect and is known (page 1, paragraph 4). Regarding claim 122, Naito taught exatecan: inhibits topoisomerase I more than SN-38; and also has higher in vitro cytocidal activity against various cancer cells (page 1, paragraph 4). Regarding claims 123-129, Naito taught the anti-HER2 ADC targeting antibody as trastuzumab (page 10, paragraph 109, Figure 1 and 2), wherein: 1) the antibody comprises a heavy chain consisting of the amino acid sequence of SEQ ID NO: 1 and a light chain consisting of the amino acid sequence of SEQ ID NO: 2; 2) the antibody of 1) wherein the antibody lacks a lysine residue at the carboxyl terminus of the heavy chain; or 3) the antibody comprised a heavy chain consisting of an amino acid sequence consisting of amino acid residues 1 to 449 of SEQ ID NO: 1 and a light chain consisting of an amino acid sequence consisting of amino acid residues 1 to 214 of SEQ ID NO: 2 (pages 9-10, paragraphs 98-100). Regarding claim 128, Naito taught it is known that a lysine residue at the carboxyl terminus of the heavy chain of an antibody produced in a cultured mammalian cell is deleted, however, such deletion and modification of the heavy chain sequence do not affect the antigen-binding affinity and the effector function (the activation of a complement, the antibody-dependent cellular cytotoxicity, etc.) of the antibody (page 16, paragraphs 218). Regarding claim 127, the Naito antibody of SEQ ID NO:1 comprises a heavy chain variable region VH consisting of the amino acid sequence of 1-120 and a IgG1 constant region and from 121-450. Regarding claim 126, the Naito antibody of SEQ ID NO:2 comprises a light chain variable region VL consisting of the amino acid sequence of 1-107 and a IgG1kappa constant region and from 108-214. Regarding claims 122-129, 157-159, Naito taught the anti-HER2 trastuzumab linked exatecan ADC of example 50 was more effective than trastuzumab at inhibiting HER2 expressing breast tumor growth in vivo (Fig. 8). Regarding claims 160, Naito taught the anti-HER2 trastuzumab linked exatecan ADC of example 50 was effective at inhibiting breast tumor growth in vivo with low HER2 expression, while trastuzumab and a different ADC of trastuzumab linked emtansine were not effective (page 102, paragraph 754-757 and Fig.6). Regarding claims 161, Naito taught HER2 is overexpressed in gastric cancer (pages 1-2, paragraph 8). Regarding claim 163, Naito taught administration of the anti-HER2 trastuzumab linked exatecan ADC of example 50 was dose-dependently effective at inhibiting HER2 expressing lung cancer tumor growth in subjects in vivo (Fig. 11). Regarding claims 122-129 and 162, Naito taught administration of the anti-HER2 trastuzumab linked exatecan ADC of example 50 was dose-dependently effective at inhibiting HER2 expressing ovarian cancer tumor growth in subjects in vivo (Fig. 14). Regarding claims 122-129 and 161, Naito taught administration of the anti-HER2 trastuzumab linked exatecan ADC of example 50 was dose-dependently effective at inhibiting HER2 expressing gastric cancer tumor growth in subjects in vivo (Fig. 7). Regarding claims 122-129, Naito taught administration of the anti-HER2 trastuzumab linked exatecan ADC conjugate (50) did not cause weight loss in vivo (page 102, paragraph 759).
Naito did not teach a method of treating cancer wherein the HER2 ADC conjugated to Formula I is administered in combination with a PARP inhibitor; but this is obvious in view of Goldenberg.
Regarding claims 122-129, 150-152, 154, 157-159, and 165-169, Goldenberg taught the ADC of IMMU-132, which is an anti-TROP2 antibody conjugated to the camptothecin derivative SN-38, in combination treatment with the PARP inhibitors olaparib, rucaparib, or talazoparib showed synergistic growth inhibition of cultured breast cancer cells when combined (page 20, paragraph 172 and Fig. 2). Goldenberg taught importantly, this synergy occurred in both BRCA1/2-mutated and -wild-type cell lines (page 20, paragraph 172). Regarding claims 122-129, 150-155, and 165-169, Goldenberg taught the PARP inhibitors for combination treatment with the ADC as olaparib, rucaparib, talazoparib, veliparib, or niraparib (page 2, paragraph 17). Regarding claims 122-129, 150-155, 157-159, and 165-169, Goldenberg taught combination IMMU-132 and olaparib was effective at inhibiting breast tumor growth in vivo (page 21, paragraph 180-181, Fig 3B-C). Regarding claims 122-129, 157-159, and 165-169, Goldenberg taught the utilization of PARP inhibitors to target triple negative breast cancer combined with topoisomerase I inhibition mediated by IMMU-132, a synergistic growth-inhibitory outcome was achieved in human triple-negative breast cancer tumor lines (page 24, paragraph 199). Regarding claims 122-129, 157-159, and 165-169, Goldenberg taught combination of PARP inhibitors and IMMU-132 will broaden the range of tumors for treatment (page 24, paragraph 199). Regarding claims 122-129, 157-159, 157-161, and 165-169, Goldenberg taught in both gastric and TNBC tumor cells, IMMU-132 specifically mediated dsDNA breaks in Trop-2-expressing cells (page 2, paragraph 11). Regarding claim 162, Goldenberg taught therapy with PARPi has resulted in sustained anti-tumor responses in ovarian cancer (page 1, paragraph 8) and treatment with the ADC for Trop-2-positive ovarian cancer (page 4, paragraph 27). Regarding claim 163, Goldenberg taught agents that inhibit topoisomerase I (Topo I), have been shown to synergize with PARPi to deter the growth of a range of human tumor cell lines, including lung cancer (pages 1-2, paragraph 10). Regarding claims 161, Goldenberg further taught treatment of gastric cancer (page 17, paragraph 145). Regarding claim 161, Goldenberg taught mice bearing Trop-2+ human gastric carcinoma xenografts (NCI-N87) were administered the ADC IMMU-132 with a drug to antibody ratio of about 7 and showed a significantly improved median survival time (MST) (page 24, paragraph 212). Regarding claims 122-129, Goldenberg taught antibodies targeting tumor-associated antigens (TAAs) other than Trop-2 may be used as ADCs in combination with PARP inhibitors (page 25, paragraph 220). Regarding claims 122-129, Goldenberg taught HER2 as a useful antigens that may be targeted (page 11, paragraph 96) and further taught that the antibody of the ADC as the HER2 targeting antibody trastuzumab (Goldenberg claim 23). Regarding claim 156, Goldenberg taught formulation of the ADC for intravenous administration (page 16, paragraph 142) and PARP inhibitors designed for oral administration (page 16, paragraph 139). Regarding claim 156, Goldenberg taught the PARP inhibitor administered separately or together with the ADC (page 1, paragraph 4). Regarding claim 156, Goldenberg taught administration of the ADC and olaparib in combination either prior to, simultaneously with or after the conjugate (page 14, paragraph 121).
Regarding instant claims 122-129, 150-153, 155, 157-163, and 165-169, it would have been obvious for a person having ordinary skill in the art to take the method of treating HER2 expressing breast cancer, gastric cancer, or low HER2 expressing breast cancer comprising administering a subject with breast, gastric, ovarian, or lung cancer an anti-HER2 targeting ADC conjugated to the camptothecin derivative exatecan ADC of Naito example 50, wherein Naito further taught the antibody comprises either: i) a heavy chain of SEQ ID NO: 1 and a light chain of SEQ ID NO: 2; or ii) consists of a heavy chain of amino acid residues 1 to 449 of SEQ ID NO: 1 and a light chain of amino acid residues 1 to 214 of SEQ ID NO: 2 – and 1) further administer a PARP inhibitor with the ADC as taught by Goldenberg; and 2) use the PARP inhibitors olaparib, rucaparib, veliparib, or niraparib.
This is obvious because:
1a) Naito taught the anti-HER2 trastuzumab linked exatecan ADC of example 50 was effective at inhibiting low HER2 expressing breast cancer and HER2 expressing breast, gastric, ovarian, and lung cancer tumor growth in vivo;
1b) Goldenberg taught PARP inhibitors combined with topoisomerase I inhibition caused the synergistic growth inhibition in cancer;
1c) Goldenberg taught the cancer targeted ADC linked camptothecin derivative SN-38 in combination with olaparib synergistically inhibits cancer cell growth
1d) Goldenberg taught antibodies targeting tumor-associated antigens (TAAs) other than Trop-2 may be used as ADCs in combination with PARP inhibitors and identified HER2 and the antibody trastuzumab as the target and targeting antibody respectively;
1e) the anti-HER2 targeting ADC conjugated to the camptothecin derivative exatecan of Naito can target HER2 expressing cancer cells and is a more potent camptothecin derivative that would provide synergistic inhibition through the same mechanism of action in PARP combination therapy; and
2a) Goldenberg taught the ADC of IMMU-132, which is conjugated to the camptothecin derivative SN-38, in combination treatment with the PARP inhibitors olaparib, rucaparib, or talazoparib showed synergistic growth inhibition of cancer cells when combined.
2b) Goldenberg taught the PARP inhibitors for combination treatment with the ADC as olaparib, rucaparib, veliparib, or niraparib.
This would produce a method of treating cancer comprising administering the anti-HER2 ADC (instant claims 123-124) linked exatecan of Naito example 50 and the PARP inhibitor olaparib (instant claims 150-151) and the PARP inhibitor rucaparib (instant claim 152), niraparib (instant claim 153), or veliparib (instant claim 155) in combination to a subject with HER2 expressing breast, gastric, ovarian, or lung cancer (instant claims 157-160 and 161-163) and low HER2 expressing breast cancer, wherein the drug linker is represented by the formula
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, wherein the anti-HER2 ADC is conjugated to the drug-linker via a thioether bond between the antibody and linker (instant claim 122), wherein the drug-linker conjugated per antibody molecule is 7.8, which is between 7 and 8 (instant claims 129 and 165-169), wherein the anti-HER2 antibody is: i) a heavy chain of SEQ ID NO: 1 and a light chain of SEQ ID NO: 2 with an identical sequence to instant SEQ ID NO:1 and 2 (instant claim 127); or ii) consists of a heavy chain of amino acid residues 1 to 449 of SEQ ID NO: 1 and a light chain of amino acid residues 1 to 214 of SEQ ID NO: 2 with an identical sequence to instant SEQ ID NO:1 of amino acid residues 1 to 449 and SEQ ID NO:2 (instant claim 128), wherein both antibodies comprise a light and heavy chain that: a) consist of identical amino acids for the CDRH1-3 to amino acid residues 26 to 33, 51 to 58, and 97-109 of instant SEQ ID NO: 1 and CDRL1-3 of amino acid residues 27 to 32, 50 to 52, and 89-97 of instant SEQ ID NO: 2 as defined by IMGT numbering (instant claim 125); and b) consist of a heavy chain variable region amino acid sequence identical to amino acids 1 to 120 of instant SEQ ID NO:1 and light chain variable region of amino acid residues 1 to 107 of instant SEQ ID NO:2 (instant claim 126). The method further meets the claim limitation of instant claims 85-89.
There is a reasonable expectation of success because:
1a) the anti-HER2 trastuzumab linked exatecan ADC of example 50 was effective at inhibiting low HER2 expressing breast cancer and HER2 expressing breast, gastric, and ovarian cancer tumor growth in vivo;
1b) the HER2 targeting ADC would target the camptothecin derivative exatecan to inhibit topoisomerase in the HER2 expressing breast or gastric cancer cells and allow the PARP inhibitors to synergistically inhibit cancer cell growth;
1c) it is known from Goldenberg that cancer targeted ADCs linked to a camptothecin derivative, SN-38, in combination with olaparib synergistically inhibits cancer cell growth
1d) the anti-HER2 targeting ADC conjugated to the camptothecin derivative exatecan of Naito can target HER2 expressing cancer cells and contains a potent camptothecin derivative that would provide synergistic inhibition through the same mechanism of action in PARP combination therapy;
1e) the anti-HER2 targeting ADC conjugated to the camptothecin derivative exatecan of Naito can target HER2 expressing cancer cells and is a more potent camptothecin derivative that would provide synergistic inhibition through the same mechanism of action in PARP combination therapy;
2a) PARP inhibitors combined with topoisomerase I inhibition mediated by the camptothecin derivative linked HER2 targeting ADC would synergistically inhibit cancer cell growth, wherein the camptothecin derivative exatecan would be targeted to HER2 expressing breast, gastric, or ovarian cancer cells; and
2b) combination treatment of PARP inhibitors and camptothecin derivatives are known to synergistically inhibit cancer cell growth and all of the inhibitors are PARP inhibitors.
.
Regarding instant claim 156, it would have been obvious for a person having ordinary skill in the art to take the method of treating HER2 expressing breast, gastric, ovarian, or lung cancer with the anti-HER2 ADC trastuzumab linked exatecan of example 50 of Naito and the PARP inhibitor rucaparib of Naito and Goldenberg above – and separately administer the ADC and PARP inhibitor that are separately contained in different formulations and administer them simultaneously.
This is obvious because: 1) Goldenberg taught formulation of the ADC for intravenous administration, PARP inhibitors are designed for oral administration, and administration of the ADC and rucaparib in combination simultaneously.
This would produce a method of treating breast, gastric, ovarian, or lung cancer comprising administering the anti-HER2 ADC trastuzumab linked exatecan of example 50 and the PARP inhibitor olaparib, rucaparib, niraparib, or veliparib in combination to a subject with breast or gastric cancer, wherein the drug linker is represented by the formula
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, wherein the drug-linker conjugated per antibody molecule is 7.8, wherein the trastuzumab antibody is an antibody comprising a heavy chain comprising of the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2, and wherein the ADC and PARP inhibitor are separately contained in different formulations and administered simultaneously (instant claim 156).
There is a reasonable expectation of success because: 1a) the ADC is formulated for intravenous administration and the olaparib is formulated for oral administration, thus they would be contained in separate formulations and administered separately because they are administered through different routes of administration; 1b) simultaneous administration would allow PARP to be inhibited in the cells by rucaparib at the same time as the topoisomerase I is inhibited by the exatecan in the HER2 targeted ADC to synergistically kill the cancer cells.
Response to Arguments
Applicant argues new claims 102-181 have been added, and these claims are also believed to be commensurate in scope with the empirical evidence of record showing that the claimed combination of an antibody-drug conjugate with the recited drug-linker and a PARP inhibitor (PARPi) provide unexpectedly improved pharmacological effects over either recited compound alone.
Applicant argues independent claim 122 recites, "wherein if the cancer is gastric cancer the method does not comprise administering an anti-HER2 ADC simultaneously or sequentially with olaparib or a pharmaceutically acceptable salt of olaparib to the subject." MPEP § 2145 states that proffered evidence "must be reasonably commensurate in scope with the claimed invention" ( emphasis added), and here the evidence of record reasonably supports the unexpectedness of other combinations of ADCs and PARP inhibitors within the scope of claim 122
In response, Applicant's arguments filed 3/6/2026 have been fully considered but they are not persuasive. Regarding unexpected results and their scope, MPEP 716.02(d) states whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." Thus, while the claims have surprising results for:
1) a method of treatment of breast cancer and ovarian cancer comprising administering the claimed ADC structure conjugated to various antibodies in combination with PARP inhibitors;
2) a method of treatment of cancer comprising administering the claimed ADC structure conjugated to various antibodies in combination with talazoparib; and
3) a method of treatment of gastric cancer comprising administering the claimed ADC structure conjugated to a HER2 antibody in combination with talazoparib,
the claims do not have surprising results for treating cancers other than breast cancer or ovarian cancer with ANY PARP inhibitor. While the species tested show surprising results for: 1) breast or ovarian cancer with all antibody ADCs and all PARP inhibitor combinations tested; 2) all antibody ADCs and talazoparib in combination in all cancers tested; and 3) a HER2 antibody ADC and talazoparib in combination in gastric cancer,
it is unpredictable if: A) olaparib will have surprising results in vivo in other cancers; B) if gastric cancer will have surprising results with PARP inhibitors other than talazoparib; or C) if rucaparib, niraparib, or veliparib will have surprising results in vivo in other cancers. Instant claims 1-8, 29-40, 85-89, 102-113,115-121, and 154 are not included in the 103 rejection in light of the surprising results.
Olaparib combination with the HER2 targeted ADC in vivo in gastric cancer NCI-N87 tumors displays a less than additive response in vivo in instant Fig. 20. It is unclear if other cancers would also show a response similar to breast cancer or gastric cancer in vivo.
While Table 1 shows a synergy score of 5.05 (instant specification, page 135, paragraph 256) with the combination of olaparib and the HER2 targeted ADC in the same gastric cancer cell line of NCI-N87, the claims require administration of the combination to a subject. Additionally, this demonstrates the synergy scores obtained in the instant disclosure for in vitro cell-based experiments do not reflect the synergy in vivo in a subject. Thus, in vitro synergism results would require in vivo confirmation. Further, there would not be surprising results for the full scope of the invention claimed.
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 122-129 and 156-163 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-9, 11-17 and 71-89 of copending Application No. 18/248,283. Although the claims at issue are not identical, they are not patentably distinct from each other because: ‘283 taught a pharmaceutical product comprising an anti-HER2 ADC and a PARP1 selective inhibitor for administration in combination, wherein the drug-linker of the formula below:
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, is conjugated to the HER2 antibody in copending claim 1 and a method of treating cancer with the anti-HER2 ADC conjugate and PARP1 selective inhibitor in combination in copending claim 71, which anticipate instant claims 122-124. ‘283 taught the method can be used as a treatment of breast cancer, HER2 low expressing breast cancer, gastric cancer, ovarian cancer, or lung cancer in copending claims 73, 75, 80, 82, and 85 which anticipate instant claims 157-163. ‘283 copending claim 12 taught the anti-HER2 antibody as comprising a heavy chain consisting of an amino acid sequence represented by SEQ ID NO: 1 and a light chain consisting of an amino acid sequence represented by SEQ ID NO: 2 with the VH and VL and CDR residues outlined in copending claims 10-12, which is identical instant SEQ ID NO:1 and instant SEQ ID NO:2 and contains the VH and VL and CDR residues as instant claims 125-127. ‘283 copending claim 11 taught the anti-HER2 antibody as comprising a heavy chain consisting of an amino acid sequence represented by SEQ ID NO: 11 and a light chain consisting of an amino acid sequence represented by SEQ ID NO:2, which is identical the anti-HER2 antibody in instant claim 128. ‘283 taught the average number of units of the drug-linker conjugated per antibody molecule in the antibody-drug conjugate is in the range of from 7 to 8, which anticipates instant claims 129. ‘283 copending claim 17 taught a combined preparation comprising the anti-HER2 antibody-drug conjugate and the PARP1 selective inhibitor, for sequential administration, which would anticipate instant claim 156 because a sequential administration would require the initial administration of the anti-HER2 ADC to not have the PARP inhibitor in the formulation.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant argues co-pending application U.S. Appl. 18/248,283 has a priority date and U.S. filing date that is later than the respective priority date and filing date of
the present application. MPEP § 804(I)(B )(1 )(b )(i) instructs, "[i ]fa provisional non-statutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing date, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent, thereby converting the provisional non-statutory double patenting rejection in the other application into a nonstatutory double patenting rejection upon issuance of the patent."
In response, Applicant's arguments filed 3/6/2026 have been fully considered but they are not persuasive. The present claims still have a 103 rejection above and are not in condition for allowance.
Claims 122-129, 150, 152-153, 155-163, and 165-169 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 and 71-89 of copending Application No. 18/248,283 in view of US 20170209594 (Goldenberg DM et al. reference of record).
The claims of copending ‘283 teach the limitations of claims 122-129 and 156-163 for the reasons set forth above.
copending ‘283 is described above.
While ‘283 taught the combination cancer treatment of an anti-HER2 ADC of formula I with a PARP inhibitor, ‘283 does not teach the PARP inhibitor as rucaparib, niraparib, talazoparib, or veliparib, but this is obvious in view of Goldenberg.
Goldenberg is described above.
Regarding instant claims 150, 152-153 and 155, and 165-169, it would have been obvious for a person having ordinary skill in the art to take the method of treating gastric cancer with the combination of a PARP1 inhibitor and an anti-HER2 ADC linked exatecan of formula I in copending claims 1, 71, and 73 – and specifically use the PARP inhibitors olaparib, rucaparib, talazoparib, veliparib, or niraparib that are taught by Goldenberg to synergistically kill cancer cells in combination with a ADC conjugated to a camptothecin derivative.
This is obvious because: 1) Goldenberg taught the ADC of IMMU-132, which is conjugated to the camptothecin derivative SN-38, in combination treatment with the PARP inhibitors olaparib, rucaparib, or talazoparib showed synergistic growth inhibition of cancer cells when combined; and 2) Goldenberg taught the PARP inhibitors for combination treatment with the ADC as olaparib, rucaparib, talazoparib, veliparib, or niraparib.
This would produce a method of treating cancer comprising administering the anti-HER2 ADC linked exatecan of formula I and the PARP inhibitor rucaparib (instant claim 150 and 152), niraparib (instant claim 153), or veliparib (instant claim 155 and 165-169), in combination to a subject with gastric cancer, wherein the drug linker is represented by the formula
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.
There is a reasonable expectation of success because: 1) PARP inhibitors combined with Topoisomerase I inhibition mediated by the camptothecin derivative linked HER2 targeting ADC would synergistically inhibit cancer cell growth, wherein the camptothecin derivative exatecan would be targeted to HER2 expressing gastric cancer cells; 2) combination treatment of PARP inhibitors and camptothecin derivatives are known to synergistically inhibit cancer cell growth and all of the inhibitors are PARP inhibitors.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant argues co-pending application U.S. Appl. 18/248,283 has a priority date and U.S. filing date that is later than the respective priority date and filing date of
the present application. MPEP § 804(I)(B )(1 )(b )(i) instructs, "[i ]fa provisional non-statutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing date, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent, thereby converting the provisional non-statutory double patenting rejection in the other application into a nonstatutory double patenting rejection upon issuance of the patent."
In response, Applicant's arguments filed 3/6/2026 have been fully considered but they are not persuasive. The present claims still have a 103 rejection above and are not in condition for allowance.
Conclusion
Claim 154 is objected to as being dependent upon a rejected base claim, but would be allowable is rewritten in independent form, including all of the limitations of the base claim and any intervening claims.
Claims 1-8, 29-40, 85-89, 102-113, and 115-121 have allowable subject matter based on surprising results.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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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/J.J.S./Examiner, Art Unit 1643
/Karen A. Canella/Primary Examiner, Art Unit 1643
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