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 .
Claim Status
Claims 1, 9, 11-17, and 77-97 are pending.
Claims 1, 9, and 11-17 are examined herein.
Claims 77-97 are withdrawn (see restriction/election below).
Priority
This application is filed 12/23/2022, and claims the benefit of domestic priority as below:
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Information Disclosure Statements
Four references from IDS(s) received on 2/21/2023, 4/24/2024, 7/16/2025, and 1/13/2026 have been considered unless marked with a strikethrough.
Election/Restrictions
Applicant elects Group I, claims 1, 9, 11-17, is drawn to pharmaceutical products comprising anti-HER2 antibody drug conjugate and an ATR inhibitor, without traverse in the reply field on 04/03/2026 is acknowledged. Claims 77-97 (Group II) are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected method of use, there being no allowable generic or linking claim.
Applicant elects the name and structure of one species of the claimed anti-HER2 antibody drug conjugate as an anti-HER2 antibody comprising a heavy chain comprising a heavy chain variable region consisting of an amino acid sequence of SEQ ID NO: 9 and a light chain comprising a light chain variable region consisting of an amino acid sequence of SEQ ID NO: 10, and the name and structure of one species of the claimed ATR inhibitor as AZD6738 as the species in the reply field on 04/03/2026 is acknowledged.
The claims 1, 9, and 11-17 are readable on the elected species, as asserted by the applicant asserts.
If the elected specie is not identified in the prior arts, the elected specie would be allowable if
an independent claim were drafted with that specie alone. (see MPEP 802.03)
The elected specie was identified in the prior art. Accordingly, claims 1, 9, and 11-17 will be examined on their merits. With respect to the expanded species, the art is rejected under 35 USC 103 below.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because it does not contain a "Sequence Listing" as a separate part of the disclosure or a CRF of the “Sequence Listing.”.
Required response - Applicant must provide:
A "Sequence Listing" part of the disclosure; together with
An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(a)(2);
A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 1.821(a)(4); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(a)(3).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
If the "Sequence Listing" part of the disclosure is submitted according to item 1) c) or d) above, applicant must also provide:
A CRF in accordance with 37 CFR 1.821(e)(1) or 1.821(e)(2) as required by 1.825(a)(5); and
A statement according to item 2) a) or b) above.
Specification
The disclosure is objected to because of the following informalities:
The amino acid sequence disclosure do not comply with the applicable sequence listing requirement of 37 CFR 1.821-1.825 and MPEP 2422-2426. (see Nucleotide and/or Amino Acid Sequence Disclosures section above)
Appropriate correction is required.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 is objected to because the term “wherein A” should be “wherein a”.
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.
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.
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.
Although the disclosure lacks the applicable sequence listing requirement, for purposes of examination, recited SEQ ID NOs in the claims are interpreted based on the amino acid sequences depicted in the drawings.
Claim(s) 1, 9, and 11-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Naito et al (EP 3101032 B1, pub’d 1/16/2019, IDS cited as WO 2015/115091 A1), in view of Foote (WO 2011/154737 A1, pub'd 12/15/2011, IDS cited).
With respect to independent claim 1, the claim recites that a pharmaceutical product comprising an anti-HER2 antibody-drug conjugate and an ATR inhibitor for administration in combination, wherein the anti-HER2 antibody-drug conjugate comprises a drug-linker conjugated to an anti-HER2 antibody, wherein the drug-linker (i.e., Formula) wherein represents the connecting position to the anti-HER2 antibody and the drug-linker is conjugated to the anti-HER2 antibody via a thioether bond wherein the anti-HER2 antibody comprises a heavy chain comprising a CDRH1 consisting of an amino acid sequence of SEO ID NO: 3, a CDRH2 consisting of an amino acid sequence of SEO ID NO: 4, and a CDRH3 consisting of an amino acid sequence of SEO ID NO: 5, and a light chain comprising a CDRL 1 consisting of an amino acid sequence of SEO ID NO: 6, a CDRL2 consisting of an amino acid sequence consisting of amino acid residues 1 to 3 of SEO ID NO: 7, and a CDRL3 consisting of an amino acid sequence of SEO ID NO: 8 and wherein the ATR inhibitor is a compound selected from specific compounds including AZD6738, or a pharmaceutically acceptable salt thereof.
Naito teaches 1) a pharmaceutical product comprising an anti-HER2 antibody drug conjugate (ADC) (paragraphed [0001]), 2) a humanized anti-HER2 antibody conjugated to a antitumor agent, camptothecin, that inhibits topoisomerase I (paragraphed [0002]-[0003]), 3) the anti-HER2 antibody may be trastuzumab (paragraphed [0010]), 4) to identify SEQ ID NO:1 as the humanized anti-HER2 antibody heavy-chain sequence and SEQ ID NO:2 as the corresponding light-chain sequences, trastuzumab as comprising heavy-chain residues 1-450 of SEQ ID NO:1 and light-chain residues 1-214 of SEQ ID NO:2 (sequence listing section). Naito’s sequence correspondence: instant SEQ ID No: 3 (residues 26-33 of SEQ ID NO 1); instant SEQ ID No: 4 (residues 51-58 of SEQ ID NO 1); instant SEQ ID No: 5 (residues 97-109 of SEQ ID NO 1); instant SEQ ID No: 6 (residues 27-32 of SEQ ID NO 2); instant SEQ ID No: 7 (residues 50-56 of SEQ ID NO 2); and instant SEQ ID No: 8 (residues 89-97 of SEQ ID NO 2) (sequence listing section).
Accordingly, Naito’s disclosure of the trastuzumab heavy and light chain sequences teaches the CDR limitations recited in claim 1. The presently assigned SEQ ID numbers do not represent different antibodies. They identify specified portions of the full trastuzumab chain sequences disclosed in Naito. Therefore, Naito teaches the claimed anti-HER2 antibody, drug-linker architecture, the thioether linkage, and the anti-HER2 ADC pharmaceutical product.
Naito fails to teach administering the disclosed anti-HER2 antibody drug conjugate in combination with an ATR inhibitor, including any of the ATR inhibitor compounds recited in claim 1.
Foote teaches 1) morpholino-pyrimidine ATR inhibitors for cancer therapy, including the compounds recited in claim 1 and pharmaceutically acceptable salts thereof (claims 8 and 9), 2) ATR inhibitors may be used in combination with other oncology treatments including topoisomerase inhibitors such as topotecan and camptothecin; (line 19 page 45 – line 25 page 47) , 3) ATR inhibitors have the potential to sensitize tumor cells to DNA damage inducing chemotherapeutic agents, induce selective tumor cell killing and produce therapeutic benefit when combined with cytotoxic agents (lines 29-32 page 3).
It would have been obvious to a PHOSITA at the time of the invention to administer Naito’s anti-HER2 ADC in combination with an ATR inhibitor of Foote because Naito teaches targeted delivery of an exatecan derived topoisomerase I inhibitor to HER2 tumor cells, while Foote teaches combining ATR inhibitors with topoisomerase inhibitors to sensitize tumor cells to DNA damaging chemotherapy, increase selective tumor cell killing, and potentially improve antitumor activity. Thus, a person of ordinary skill would have been motivated to make the combination to preserve Naito’s anti-HER2 targeted delivery while obtaining Foote’s tumor sensitizing effect and would have had a reasonable expectation of success because Naito shows delivery of an active topoisomerase I inhibitor and Foote identifies topoisomerase inhibitors as suitable combination with ATR inhibitors, and such combination would have been expected to retain its known function.
The references is directed to the same field of endeavor and address related to the application. The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham.
Examples of rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Consistently, applying KSR example rationale (A) in the independent claim 1, it would have been prima facie obvious to combine targeted delivery of an exatecan derived topoisomerase I inhibitor to HER expressing tumor cells taught by Naito, and combining ATR inhibitors with topoisomerase inhibitors to sensitizing tumor cells to DNA -damaging therapy taught by Foote, yielding predictable results as increasing selective tumor cell killing and potentially improving antitumor activity.
With respect to claim 9, the claim recites that the ATR inhibitor is AZD6738 or a pharmaceutically acceptable salt thereof.
Naito fails to teach administering the disclosed anti-HER2 antibody drug conjugate in combination with an ATR inhibitor.
Foote teaches the specific ATR inhibitor compound corresponding to AZD6738 (i.e., 4-{4-[(3R)-3-Methylmorpholin-4-yl]-6-[((R)-S-methylsulfonimidoyl)methyl]pyrimidin-2-yl}-1H-pyrrolo[2,3-b]pyridine) and pharmaceutically acceptable salts thereof (claim 8). Therefore, claim 9 would have been obvious for the reason stated above with respect claim 1.
With respect to claims 11-13, the claim recites that the anti-HER2 antibody comprises 1) a heavy chain comprising a heavy chain variable region consisting of an amino acid sequence of SEQ ID NO: 9 and a light chain comprising a light chain variable region consisting of an amino acid sequence of SEQ ID NO: 10 in claim 11; 2) a heavy chain comprising a heavy chain variable region consisting of an amino acid sequence of SEQ ID NO: 1 and a light chain comprising a light chain variable region consisting of an amino acid sequence of SEQ ID NO: 2 in claim 12; and 3) a heavy chain comprising a heavy chain variable region consisting of an amino acid sequence of SEQ ID NO: 11 and a light chain comprising a light chain variable region consisting of an amino acid sequence of SEQ ID NO: 2 in claim 13.
Naito teaches the heavy chains of SEQ IF NO: 1 contains the heavy chain variable reigns of the instant SEQ ID NO: 9, SEQ ID NO: 1 and instant SEQ ID NO: 11, and the light chains of SEQ IF NO: 2 contains the light chain variable reigns of the SEQ ID NO: 10, SEQ ID NO: 2 (sequence listing section). Thus, the antibodies recited in claims 11-13 are not separate antibody species based on different variable region sequences.
For example, Naito teaches 1) the instant SEQ ID NO: 9 corresponds to N-terminal residues 1-120 of SEQ ID NO: 1 of Naito; and the instant SEQ ID NO: 10 corresponds to N-terminal residues 1-107 of SEQ ID NO: 2 of Naito (sequence listing section); 2) the instant SEQ ID NO: 1 corresponds to N-terminal residues 1-450 of SEQ ID NO: 1 of Naito; and the instant SEQ ID NO: 2 corresponds to N-terminal residues 1-214 of SEQ ID NO: 2 of Naito (sequence listing section); and 3) the instant SEQ ID NO: 11 corresponds to N-terminal residues 1-449 of SEQ ID NO: 1 of Naito; and the instant SEQ ID NO: 2 corresponds to N-terminal residues 1-214 of SEQ ID NO: 2 of Naito (sequence listing section). Naito further teaches the corresponding trastuzumab heavy and light chain sequences (sequence listing section). Therefore, the claimed variable regions are portions of the same trastuzumab chains already disclosed and used in R1, rather than modifications that must independently be selected. Therefore, claims 11-13 would have been obvious for the reason stated above with respect claim 1.
With respect to claim 14, the claim recites that the anti-HER2 antibody-drug conjugate represented by the following formula wherein' Antibody' indicates the anti-HER2 antibody conjugated to the drug-linker via a thioether bond, and n indicates an average number of units of the drug-linker conjugated per antibody molecule in the antibody-drug conjugate, wherein n is in the range of from 7 to 8.
Naito teaches the corresponding exatecan drug, linker, thioether attachment to the anti-HER2 antibody (paragraph [0002], and [0018]). Naito further teaches the ranges of 2-8 and 3-8 encompass the claimed range of 7-8 (paragraph [0018]).. It would have been obvious to select a loading in the overlapping 7-8 region though routine optimization because Naito teaches that loading is controllable and that loading though eight are preferred.
With respect to claim 15, the claim recites that the anti-HER2 antibody-drug conjugate is trastuzumab deruxtecan (DS-8201).
Naito teaches the trastuzumab based ADC having the exatecan derived topoisomerase I inhibitor payload, the claimed linker arrangement, thioether attachment, and high drug loading characteristic of trastuzumab deruxtecan (paragraph [0292]-[0325]). Therefore, claim 15 would have been obvious for the reason stated above with respect claim 1.
With respect to claims 16 and 17, the claims recite that the product is a composition comprising the anti-HER2 antibody-drug conjugate and the ATR inhibitor, for sequential or simultaneous administration.
Naito teaches other anti-cancer agents used for such purpose may be administered to an individual simultaneously with, separately from, or subsequently to the antibody-drug conjugate, and may be administered while varying the administration interval for each (paragraph [0280]). Therefore, claims 16 and 17 would have been obvious for the reason stated above with respect claim 1.
Conclusion
Claims 1, 9, and 11-17 are rejected.
Claim 1 is objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEONG JONG KIM whose telephone number is (571)272-6918. The examiner can normally be reached 7:00am-3:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton A. Brooks can be reached at 571-270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SEONG JONG KIM/ Examiner, Art Unit 1621
/CLINTON A BROOKS/ Supervisory Patent Examiner, Art Unit 1621
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