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 .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 3-7, 11, 13-14, 16, and 19-20) and the below-listed species in the reply filed on 12/29/2025 is acknowledged.
Elected Species:
Anti-HER3 antibody comprising HCDRs 1-3, LCDRs 1-3, VH, and VL sequences as set forth in SEQ ID NOs: 21-23, 24-26, 7, and 8, respectively.
An effector molecule that is an anti-tumor agent.
Antibody-drug conjugate designated as HER3-29-A9.
Cancer that is breast cancer.
Claim Status
Claims 1-2, 8, and 17 have been cancelled, as requested in the amendment filed on 12/29/2025. Following the amendment, claims 3-7, 9-16, and 18-20 are pending in the instant application.
Claims 9-10, 12, 15, and 18 stand as withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventions in the Response filed 12/29/2025, there being no allowable generic or linking claim.
Claims 3-7, 11, 13-14, 16, and 19-20 are under examination in the instant office action.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55 for foreign priority application CN202011097383.0. However, it is noted that the claim to foreign priority has not been perfected as no English translation of the foreign priority document has been provided.
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in China on 10/08/2021. It is noted, however, that applicant has not filed a certified copy of the CN202111171200.X application as required by 37 CFR 1.55.
Claims 3-7, 11, 13-14, 16, and 19-20 have an effective filing date of October 14, 2021 corresponding to PCT/CN2021/123733, as certified copies and/or English translations of the foreign priority documents have not been provided and therefor the claim to foreign priority has not been perfected.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/14/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code at Page 24. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The specification is further objected to for the use of the terms FACS, Megalign, DNASTAR, Sepharose, Lipofectamine, and GraphPad Prism, which are trade names or marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 3 and 7 are objected to because of the following informalities: limitations of the claims are presented as lists designated by a., b., c., etc. and as such the claims comprise periods that are not used to indicate an abbreviation or the end of a sentence. Applicant may obviate the objection by amending the claims to remove the periods such that such the limitations are presented as lists designated by, for example, a), (a), or the like. Appropriate correction is required.
Claim Interpretation
With regard to the sequence language utilized in the instant claims, the following are noted:
Under broadest reasonable interpretation (BRI), the recitation of, for example, “comprises HCDR1, HCDR2, and HCDR3 set forth in SEQ ID NO: 21, SEQ ID NO: 22 and SEQ ID NO: 23” is being interpreted as closed sequence language; HCDR1 must comprise full-length SEQ ID NO: 21, HCDR2 must comprise full-length SEQ ID NO: 22, and HCDR3 must comprise full-length SEQ ID NO: 23. Such language pertains to claims 1 and 14.
Under BRI, the recitation of, for example, “an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 7” is interpreted as any amino acid sequence having 90% identity to full-length SEQ ID NO: 7; an amino acid sequence meeting such a limitation may be truncated/mutated relative to SEQ ID NO: 7, so long as the overall identity is at least 90%. Furthermore, under BRI the recitation of, for example, “an amino acid sequence set forth in SEQ ID NO: 7” is being interpreted as open sequence language; any amino acid sequence comprising at least two consecutive amino acids of SEQ ID NO: 7 is sufficient to satisfy the limitation due to the recitation of “an amino sequence”. Such language pertains to claims 5-6.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 5-7, 11, and 13 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claims 5-7 and 11, the phrase "preferably" renders the claims indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). It is unclear if the claim limitations following the recitation of “preferably” are required by the claim, or if they are merely exemplary and therefore not required.
Further regarding claim 7, the claim contains the trademark/trade name FACS. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a flow cytometer/cell separator/cell sorter and, accordingly, the identification/description is indefinite.
With regard to claim 13, the phrase "optionally further substituted with one or more substituents" with regard to W and L3 renders the claims indefinite because the phrase introduces many possible structural iterations which may compound on each other, and as such there is a high level of ambiguity regarding the possible structures incorporated by claim 13. It is unclear as to which optional substituents, and how many of them, may or may not be present for any given antibody drug conjugate structure.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 3-7, 11, and 16 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO 2023/051814 A1 (herein after referred to as "Xu"; US equivalent US 2025/0000989 A1 relied upon for translation) .
The applied reference has a common Applicant and Inventor 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). This rejection under 35 U.S.C. 102(a)(2) 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) if the same invention is not being claimed; 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 in the reference 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.
Xu discloses a pyrrolobenzodiazepine (PBD) derivative and a conjugate, preparation method and use thereof (Abstract); antibody-drug conjugates (ADCs) of the invention are represented by the formula Pc-[L-D]y wherein, generally, Pc is an antibody, L is a linker, y is drug loading from 1 to 10, and D is represented by the formula reproduced below (i.e., D is a pyrrolobenzodiazepine (PBD) dimer payload, an anti-tumor agent):
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Xu further discloses exemplary embodiments of ADCs of the invention, exemplary structures reproduced below (see Pages 27-30), wherein the Pc (i.e., antibody) may be an anti-HER3 antibody comprising SEQ ID NOs: 5 and 6 (Paragraphs 0155-0156); it is noted that SEQ ID NOs: 5 and 6 correspond to anti-HER3 antibody HER3-29 (Paragraph 0407). Xu SEQ ID NOs: 5 and 6 are exact matches to instantly claimed SEQ ID NOs: 28 and 27, respectively; it is further noted that Xu SEQ ID NOs: 5 comprises exact matches to instantly claimed SEQ ID NOs: 24-26 and 8, and reference application SEQ ID NO: 6 comprises exact matches to instant SEQ ID NOs: 21-23 and 7. Additionally, it is disclosed that HER3-29 is a human antibody in the instant specification; thus, the identical antibody as disclosed by Xu is fully human. Furthermore, it is well established in the art that the affinity of antibodies is determined by their structure, notably the CDR sequences, and as such the HER3-29 antibody of Xu would therefore have at least one of the characteristics of instant claim 7 owing to the HER3-29 antibody of Xu having the instantly claimed CDRs. Xu further discloses pharmaceutical compositions, comprising a therapeutically effective amount of the antibody-drug conjugate or the pharmaceutically acceptable salt thereof according to the invention, or the compound represented by formula (DL) or the pharmaceutically acceptable salt thereof according to the invention, and a pharmaceutically acceptable carrier, diluent, or excipient (Paragraph 0288). Xu further provides the antibody-drug conjugate or the pharmaceutically acceptable salt thereof, or the
compound represented by formula (DL) or the pharmaceutically acceptable salt thereof, or the aforementioned pharmaceutical composition for use as a medicament and/or for use in the preparation of a medicament, wherein such a medicament is useful for treating a tumor or cancer (Paragraphs0289-0295); it is noted that this reads on a kit, which is an article or articles for a specific use. As such, Xu anticipates instant claims 3-7, 11, 16, and 19.
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.
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.
Claims 13-14 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2023/051814 A1 (herein after referred to as "Xu"; US equivalent US 2025/0000989 A1 relied upon for translation) in view of CN 112125915 A (original document published Dec. 2020; using US equivalent US 2022/0411436 A1 for translation; herein after referred to as Zhu).
Xu discloses a pyrrolobenzodiazepine (PBD) derivative and a conjugate, preparation method and use thereof (Abstract); antibody-drug conjugates (ADCs) of the invention are represented by the formula Pc-[L-D]y wherein, generally, Pc is an antibody, L is a linker, y is drug loading from 1 to 10, and D is represented by the formula reproduced below (i.e., D is a pyrrolobenzodiazepine (PBD) dimer payload, an anti-tumor agent):
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Xu further discloses exemplary embodiments of ADCs of the invention, exemplary structures reproduced below (see Pages 27-30), wherein the Pc (i.e., antibody) may be an anti-HER3 antibody comprising SEQ ID NOs: 5 and 6 (Paragraphs 0155-0156); it is noted that SEQ ID NOs: 5 and 6 correspond to anti-HER3 antibody HER3-29 (Paragraph 0407). Xu SEQ ID NOs: 5 and 6 are exact matches to instantly claimed SEQ ID NOs: 28 and 27, respectively; it is further noted that Xu SEQ ID NOs: 5 comprises exact matches to instantly claimed SEQ ID NOs: 24-26 and 8, and reference application SEQ ID NO: 6 comprises exact matches to instant SEQ ID NOs: 21-23 and 7. Thus, Xu teaches ADCs comprising anti-HER3 antibody HER3-29.
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However, the reference application does not teach/suggest an ADC having the structure corresponding to instant ADC designated as HER3-29-A9, reproduced below.
Zhu teaches that commonly used drug or toxins in ADCs include highly toxic toxins, such as MMAE, T-DM1, PBD, etc., which not only are highly toxic but also have narrow treatment windows even in the form of ADCs (Paragraph 0006). The invention of Zhu is drawn to camptothecin derivatives with increased anti-tumor activity and decreased toxicity, which can improve the safety and effectiveness of the ADC drugs with an excellent anti-tumor curative effect; based on a comprehensive understanding of the structure-activity relationship between camptothecin derivatives and ADC drugs, the inventors designed and synthesized a series of camptothecin derivatives and their antibody conjugates with significantly improved antitumor therapeutic activity (Paragraphs 0008-0009). Zhu provides the drug-linker compound represented by the general formula (L-X-D2) or its tautomer, mesomer, racemate, enantiomer, diastereomer or a mixture thereof, or a pharmaceutically acceptable salt or solvate thereof, which may include the structures shown below (Page 13), wherein the drug-linker may be reacted with an antibody to yield an antibody-drug conjugate (ADC) of general formula (Ab-L-X-Dr), which may have
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structures also shown below (Page 18).
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It is noted that the above structures read on general formula (Pc-La-Y-D) of instant claims 13-14 wherein W is C5 alkyl, L2 is a chemical bond, L3 is a four amino acid residue of Gly-Gly-Phe-Gly, Pc is an antibody, R1 is C3 cycloalkyl, R2, R5, R6, and R7 are all hydrogen, and m=0.
Zhu teaches that the antibody (i.e., Ab) may comprise, for example, a HER3 (ErbB3) antibody (Paragraph 0112). Furthermore, Zhu teaches the ADCs, compounds, pharmaceutically acceptable salts/solvates thereof, or pharmaceutical compositions thereof for use as a medicament and/or in the preparation of a medicament for the treatment of tumors/cancer (Paragraphs 0117-0119). It is noted that the compositions for use as a medicament and/or for the preparation of a medicant are considered to read on the limitation of a “kit”; a kit being an article/articles needed for a specific purpose.
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Thus, it would have been prima facie obvious to one of ordinary skill in the art at the time the instant application was filed that the ADC of Xu comprising anti-HER3 designated HER3-29 could be modified such that the drug-payload of the reference application could be substituted with the drug-payload structures disclosed by Zhu to yield an ADC comprising an anti-HER3 antibody coupled to the linker-payload structures as shown below:
wherein the resultant ADC comprises the instantly claimed structural elements as defined by instant claims 13-14; W is C5 alkyl, L2 is a chemical bond, L3 is a four amino acid residue of Gly-Gly-Phe-Gly, Pc is an antibody, R1 is C3 cycloalkyl, R2, R5, R6, and R7 are all hydrogen, and m=0, and the antibody (i.e., Ab) is an anti-HER3 (ErbB3) antibody comprising sequence of LCDRs 1-3/VL/full light chain and HCRs 1-3/VH/full heavy chain respectively, corresponding to SEQ ID NOs: 24-26, 8, 28, 21-23, 7, and 27, respectively. One would have been motivated to substitute the linker-payload of structure of the reference application for that of Zhu with a reasonable expectation of success because Zhu discloses that the camptothecin derivatives, and the ADCs thereof, have significantly improved antitumor therapeutic activity and suggests an improved therapeutic window relative to traditional payload toxins, such as PBDs. Zhu further discloses using anti-HER3 antibodies in ADCs of the invention, and thus it would have been within the purview of one having ordinary skill in the art that the anti-HER3 antibody of the reference application could have been conjugated to the payload-linkers of Zhu to arrive at an ADC, still useful in the treatment of cancer (i.e., HER3 positive cancers) wherein said ADC would reasonably be expected to have anti-tumor activity, reduced toxicity, and an improved therapeutic window. It also would have been withing the purview of one having ordinary skill in the art to provide the ADC in the form of a pharmaceutical composition, as suggested by the reference application and Zhu, and/or a kit (i.e., for use as a medicament/for the preparation of a medicant wherein the medicaments are useful in the treatment of tumors/cancer), as disclosed by Zhu.
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 3-7, 11, and 16, are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 20, and 33 of copending Application No. 18/697,301 (reference application; corresponds to WO 2023/051814 A1 and equivalent US 2025/0000989 A1). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 1 of the reference application is drawn to an antibody-drug conjugate (ADC) represented by the formula Pc-[L-D]y wherein, generally, Pc is an antibody, L is a linker, y is drug loading from 1 to 10, and D is represented by the formula reproduced below (i.e., D is a pyrrolobenzodiazepine (PBD) dimer payload):
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Claim 20 of the reference application is drawn to the ADC of claim 1, wherein the ADC is selected from a group of structures which fully specify the linker-payload (i.e., L-D) structures and wherein Pc (the antibody) that may be selected is an anti-HER3 antibody comprising light chain and heavy chain sequences set forth in SEQ ID NOs: 5 and 6, respectively. It is noted that reference application SEQ ID NOs: 5 and 6 are exact matches to instantly claimed SEQ ID NOs: 28 and 27, respectively; it is further noted that reference application SEQ ID NOs: 5 comprises exact matches to instantly claimed SEQ ID NOs: 24-26 and 8, and reference application SEQ ID NO: 6 comprises exact matches to instant SEQ ID NOs: 21-23 and 7. Claim 33 of the reference application is drawn to a pharmaceutical composition comprising a therapeutically effective amount of the ADC or pharmaceutically acceptable salt thereof of claim 1 and a pharmaceutically acceptable carrier, diluent, or excipient.
As such, the claims of the reference application reads on the antibody of instant claims 3-7, the immunoconjugate of instant claim 11 (i.e., anti-tumor agent PBD is coupled to the anti-HER3 antibody), and the pharmaceutical compositions thereof of instant claim 16.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 19 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 20, and 33 of copending Application No. 18/697,301 (reference application; corresponds to WO 2023/051814 A1 and equivalent US 2025/0000989 A1) in view of WO 2023/051814 A1 (i.e., reference application disclosure).
Claim 1 of the reference application is drawn to an antibody-drug conjugate (ADC) represented by the formula Pc-[L-D]y wherein, generally, Pc is an antibody, L is a linker, y is drug loading from 1 to 10, and D is represented by the formula reproduced below (i.e., D is a pyrrolobenzodiazepine (PBD) dimer payload):
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Claim 20 of the reference application is drawn to the ADC of claim 1, wherein the ADC is selected from a group of structures which fully specify the linker-payload (i.e., L-D) structures and wherein Pc (the antibody) that may be selected is an anti-HER3 antibody comprising light chain and heavy chain sequences set forth in SEQ ID NOs: 5 and 6, respectively. It is noted that reference application SEQ ID NOs: 5 and 6 are exact matches to instantly claimed SEQ ID NOs: 28 and 27, respectively; it is further noted that reference application SEQ ID NOs: 5 comprises exact matches to instantly claimed SEQ ID NOs: 24-26 and 8, and reference application SEQ ID NO: 6 comprises exact matches to instant SEQ ID NOs: 21-23 and 7. Claim 33 of the reference application is drawn to a pharmaceutical composition comprising a therapeutically effective amount of the ADC or pharmaceutically acceptable salt thereof of claim 1 and a pharmaceutically acceptable carrier, diluent, or excipient.
However, the claims of the reference application do not teach/suggest a kit.
It is noted that the disclosure of the reference application qualifies as prior art. The disclosure of the reference patent further discloses exemplary embodiments of ADCs of the invention (see Pages 27-30), wherein the Pc (i.e., antibody) may be an anti-HER3 antibody comprising SEQ ID NOs: 5 and 6 (Paragraphs 0155-0156); it is noted that SEQ ID NOs: 5 and 6 correspond to anti-HER3 antibody HER3-29 (Paragraph 0407). Additionally, it is disclosed that HER3-29 is a human antibody in the instant specification; thus, the identical antibody as disclosed by the reference application is fully human. Furthermore, it is well established in the art that the affinity of antibodies is determined by their structure, notably the CDR sequences, and as such the HER3-29 antibody of the reference application would therefore have at least one of the characteristics of instant claim 7 owing to the HER3-29 antibody of the reference application having the instantly claimed CDRs. The reference application further provides the antibody-drug conjugate or the pharmaceutically acceptable salt thereof, or the compound represented by formula (DL) or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition thereof for use as a medicament and/or for use in the preparation of a medicament, wherein such a medicament is useful for treating a tumor or cancer (Paragraphs 0289-0295); it is noted that this reads on a kit, which is an article or articles for a specific use.
Thus, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed that the ADCs of the reference application, which read on the antibody of instant claim 3, could be provided as a kit; i.e., the ADCs of the reference application, pharmaceutical salts thereof, and/or pharmaceutical compositions thereof for use as a medicament and/or for preparation of a medicament wherein said medicament is useful for treating a tumor or cancer as suggested by the disclosure of the reference application.
Claims 13-14 and 20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 20, and 33 of copending Application No. 18/697,301 (reference application; corresponds to US 2025/0000989 A1), as applied to claims 3-7, 11, and 16 above, in view of CN 112125915 A (original document published Dec. 2020; using US equivalent US 2022/0411436 A1 for translation; herein after referred to as "Zhu").
Claims 1, 20, and 33 of the reference application are generally drawn to antibody-drug conjugates and pharmaceutical compositions thereof, wherein said antibody-drug conjugates may comprise an anti-HER3 antibody comprising SEQ ID NOs: 5 and 6, which are exact matches to instant SEQ ID NOs: 28 and 27, respectively, and therefore comprise the LCDRs 1-3/VL and HCRs 1-3/VH, respectively, corresponding to SEQ ID NOs: 24-26, 8, 21-23, and 7, respectively.
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However, the reference application does not teach/suggest an ADC having the structure corresponding to instant ADC designated as HER3-29-A9, reproduced below.
Zhu teaches that commonly used drug or toxins in ADCs include highly toxic toxins, such as MMAE, T-DM1, PBD, etc., which not only are highly toxic but also have narrow treatment windows even in the form of ADCs (Paragraph 0006). The invention of Zhu is drawn to camptothecin derivatives with increased anti-tumor activity and decreased toxicity, which can improve the safety and effectiveness of the ADC drugs with an excellent anti-tumor curative effect; based on a comprehensive understanding of the structure-activity relationship between camptothecin derivatives and ADC drugs, the inventors designed and synthesized a series of camptothecin derivatives and their antibody conjugates with significantly improved antitumor therapeutic activity (Paragraphs 0008-0009). Zhu provides the drug-linker compound represented by the general formula (L-X-D2) or its tautomer, mesomer, racemate, enantiomer, diastereomer or a mixture thereof, or a pharmaceutically acceptable salt or solvate thereof, which may include the structures shown below (Page 13), wherein the drug-linker may be reacted with an antibody to yield an antibody-drug conjugate (ADC) of general formula (Ab-L-X-Dr), which may have
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It is noted that the above structures read on general formula (Pc-La-Y-D) of instant claims 13-14 wherein W is C5 alkyl, L2 is a chemical bond, L3 is a four amino acid residue of Gly-Gly-Phe-Gly, Pc is an antibody, R1 is C3 cycloalkyl, R2, R5, R6, and R7 are all hydrogen, and m=0.
Zhu teaches that the antibody (i.e., Ab) may comprise, for example, a HER3 (ErbB3) antibody (Paragraph 0112). Furthermore, Zhu teaches the ADCs, compounds, pharmaceutically acceptable salts/solvates thereof, or pharmaceutical compositions thereof for use as a medicament and/or in the preparation of a medicament for the treatment of tumors/cancer (Paragraphs 0117-0119). It is noted that the compositions for use as a medicament and/or for the preparation of a medicant are considered to read on the limitation of a “kit”; a kit being an article/articles needed for a specific purpose.
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Thus, it would have been prima facie obvious to one of ordinary skill in the art at the time the instant application was filed that the ADC of the reference application comprising an anti-HER3 antibody (see reference application claim 20) could be modified such that the drug-payload of the reference application could be substituted with the drug-payload structures disclosed by Zhu to yield an ADC comprising an anti-HER3 antibody coupled to the linker-payload structures as shown below:
wherein the resultant ADC comprises the instantly claimed structural elements as defined by the instant claims 13-14; W is C5 alkyl, L2 is a chemical bond, L3 is a four amino acid residue of Gly-Gly-Phe-Gly, Pc is an antibody, R1 is C3 cycloalkyl, R2, R5, R6, and R7 are all hydrogen, and m=0, and the antibody (i.e., Ab) is an anti-HER3 (ErbB3) antibody comprising sequence of LCDRs 1-3/VL/full light chain and HCRs 1-3/VH/full heavy chain respectively, corresponding to SEQ ID NOs: 24-26, 8, 28, 21-23, 7, and 27, respectively. One would have been motivated to substitute the linker-payload of structure of the reference application for that of Zhu with a reasonable expectation of success because Zhu discloses that the camptothecin derivatives, and the ADCs thereof, have significantly improved antitumor therapeutic activity and suggests an improved therapeutic window relative to traditional payload toxins, such as PBDs. Zhu further discloses using anti-HER3 antibodies in ADCs of the invention, and thus it would have been within the purview of one having ordinary skill in the art that the anti-HER3 antibody of the reference application could have been conjugated to the payload-linkers of Zhu to arrive at an ADC, still useful in the treatment of cancer (i.e., HER3 positive cancers) wherein said ADC would reasonably be expected to have anti-tumor activity, reduced toxicity, and an improved therapeutic window. It also would have been withing the purview of one having ordinary skill in the art to provide the ADC in the form of a pharmaceutical composition, as suggested by the reference application and Zhu, and/or a kit (i.e., for use as a medicament/for the preparation of a medicant wherein the medicaments are useful in the treatment of tumors/cancer), as disclosed by Zhu.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Claims 3-7, 9-16, and 18-20 are pending. Claims 9-10, 12, 15, and 18 are withdrawn. Claims 3-7, 11, 13-14, 16, and 19-20 are rejected. No claims are allowed.
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/ALYSSA RAE STONEBRAKER/Examiner, Art Unit 1642
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642