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 .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on April 23, 2026 has been entered.
Claims 1, 4-5, 7-12, 14, 19-21, 24 and 26-31 are pending and being acted upon in this Office Action.
Priority
Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file.
Specification
The substitute specification filed on April 3, 2026 will NOT be entered because a statement that the substitute specification contains no new matter is missing. Applicant must submit a proper statement that indicates the substitute specification contains no new matter each time that Applicant submitted a substitute specification.
Objection and Rejection Withdrawn
The objection to claims 1, 10, 19, 21 and 26 is withdrawn in view of the claim amendment.
The rejection of claims 1, 4-5, 7-12, 14, 19-20, 24 and 26-30 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph is withdrawn in light of the claims amendment and the argument that n cannot be 0 and definition of n as a decimal or an integer is well recognized in the field.
Claim objection
Claim 25 is objected to because of the following informality: “in need thereof” is missing after “subject”.
Claim 26 is objected to because of the following informality: “thereof” is missing after “in need”.
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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 4-5, 7-12, 14, 19-21, 24 and 26-31 are provisionally rejected on the ground of nonstatutory double patenting over claims 1-12, 18-20 of copending Application No. 18/029,075 (reference application, now allowed). Although the conflicting claims are not identical, they are not patentably distinct from each other because even though the instant claims were more specific than the ‘075 claims, the species of the instant claims 20, 21 were disclosed in the ‘075 specification and copending claim 3, 12, and thus the instant claims were not patently distinct from the ‘075 claims.
Copending 1. (Previously Presented) A pharmaceutical composition, comprising an anti-Claudin18.2 antibody drug conjugate and a buffer, wherein an anti-Claudin18.2 antibody in the anti-Claudin18.2 antibody drug conjugate comprises a heavy chain variable region and a light chain variable region, wherein: i) the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 having amino acid sequences identical to those of a heavy chain variable region set forth in SEQ ID NO: 5, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 having amino acid sequences identical to those of a light chain variable region set forth in SEQ ID NO: 6; or ii) the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 having amino acid sequences identical to those of a heavy chain variable region set forth in SEQ ID NO: 3, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 having amino acid sequences identical to those of a light chain variable region set forth in SEQ ID NO: 4; the buffer is a histidine salt buffer, which corresponds to instant claims 5, 7. The instant specification also teaches pharmaceutical composition (see para. [0039] to [0047]) comprising histidine buffer, see para. [0266].
The reference mAb1902 murine antibody heavy chain variable region set forth in SEQ ID NO: 5 is 100% identical to instant SEQ ID NO: 5, wherein the HCDR1, HCDR2 and HCDR3 are in bold.
ALIGNMENT:
Query Match 100.0%; Score 628; Length 118;
Best Local Similarity 100.0%;
Matches 118; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLQESGAELVKPGASVKLSCKASGYIFTSYWMHWVKQRPGQGLEWIGMIHPNSGSTNY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLQESGAELVKPGASVKLSCKASGYIFTSYWMHWVKQRPGQGLEWIGMIHPNSGSTNY 60
Qy 61 NEKFKGKATLTLDKSSSTAYMQLSSLPSEDSAVYYCARLKTGNSFDYWGQGTTLTVSS 118
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NEKFKGKATLTLDKSSSTAYMQLSSLPSEDSAVYYCARLKTGNSFDYWGQGTTLTVSS 118
And the mAb1902 murine antibody light chain variable region set forth in SEQ ID NO: 6 is 100% identical to instant SEQ ID NO: 6, wherein the LCDR1, LCDR2 and LCDR3 are in bold.
Query Match 100.0%; Score 592; Length 113;
Best Local Similarity 100.0%;
Matches 113; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIVLTQSPSSLTVTAGEKVTMSCKSSQSLLNSGNQKNYLTWYQQKPGQPPKLLIYWASTR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIVLTQSPSSLTVTAGEKVTMSCKSSQSLLNSGNQKNYLTWYQQKPGQPPKLLIYWASTR 60
Qy 61 ESGVPDRFTGSGSGTDFTLTISSVQAEDLAIYYCQNAYTYPFTFGSGTKLEIK 113
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ESGVPDRFTGSGSGTDFTLTISSVQAEDLAIYYCQNAYTYPFTFGSGTKLEIK 113
Or the mAb1901 murine antibody heavy chain variable region set forth in SEQ ID NO: 3 is 100% identical to instant SEQ ID NO:3, wherein the HCDR1, HCDR2 and HCDR3 are in bold.
Query Match 100.0%; Score 635; Length 120;
Best Local Similarity 100.0%;
Matches 120; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLMESGGGLVKPGGSLKLSCAASGFTFSDYGIHWVRQAPEMGLEWIAYISRGSSTIYY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLMESGGGLVKPGGSLKLSCAASGFTFSDYGIHWVRQAPEMGLEWIAYISRGSSTIYY 60
Qy 61 ADTVKGRFTMSRDNAKNTLFLQMTSLRSEDTAMYYCARGGYDTRNAMDYWGQGTSVTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADTVKGRFTMSRDNAKNTLFLQMTSLRSEDTAMYYCARGGYDTRNAMDYWGQGTSVTVSS 120
and the mAb1901 murine antibody light chain variable region set forth in SEQ ID NO: 4 is 100% identical to instant SEQ ID NO: 4, wherein the LCDR1, LCDR2 and LCDR3 are in bold.
Query Match 100.0%; Score 584; Length 113;
Best Local Similarity 100.0%;
Matches 113; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIVMTQSPSSLSVSAGEKVTMSCKSSQSLLNSGNQKNYLAWYQQKPGQPPKLLIYGASTR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIVMTQSPSSLSVSAGEKVTMSCKSSQSLLNSGNQKNYLAWYQQKPGQPPKLLIYGASTR 60
Qy 61 ASGVPDRFTGSGSGTDFTLTISSVQAEDLAIYHCQNDLYYPLTFGAGTKLELK 113
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ASGVPDRFTGSGSGTDFTLTISSVQAEDLAIYHCQNDLYYPLTFGAGTKLELK 113
Copending 2. (Previously Presented) The pharmaceutical composition according to claim 1, wherein the anti- Claudin18.2 antibody comprises a heavy chain variable region and a light chain variable region, wherein: iii) the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 set forth in SEQ ID NO: 15, SEQ ID NO: 16 and SEQ ID NO: 17, respectively, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 set forth in SEQ ID NO: 18, SEQ ID NO: 19 and SEQ ID NO: 20, respectively; or iv) the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 set forth in SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11, respectively, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 set forth in SEQ ID NO: 12, SEQ ID NO: 13 and SEQ ID NO: 14, respectively.
17/782980
18/029,075
SEQ ID NO: 15
SYWMH
SYWMH
SEQ ID NO: 16
MIHPNSGSTNYNEKFKG
MIHPNSGSTNYNEKFKGR
SEQ ID NO: 17
LKTGNSFDY
LKTGNSFDY
SEQ ID NO: 18
KSSQSLLNSGNQKNYLT
KSSQSLLNSGNQKNYLT
SEQ ID NO: 19
WASTRES
WASTRES
SEQ ID NO: 20
QNAYTYPFT
QNAYTYPFT
SEQ ID NO: 9
DYGIH
DYGIH
SEQ ID NO: 10
YISRGSSTIYYADTVKG
YISRGSSTIYYADTVKG
SEQ ID NO: 11
GGYDTRNAMDY
GGYDTRNAMDY
SEQ ID NO: 12
KSSQSLLNSGNQKNYLA
KSSQSLLNSGNQKNYLA
SEQ ID NO: 13
GASTRAS
GASTRAS
SEQ ID NO: 14
QNDLYYPLT
QNDLYYPLT
SEQ ID NO: 5
SEQ ID NO: 5
SEQ ID NO: 6
SEQ ID NO: 6
SEQ ID NO: 31
SEQ ID NO: 31
SEQ ID NO: 28
SEQ ID NO: 28
SEQ ID NO: 3
SEQ ID NO: 3
SEQ ID NO: 4
SEQ ID NO: 4
SEQ ID NO: 24
SEQ ID NO: 24
SEQ ID NO: 21
SEQ ID NO: 21
SEQ ID NO: 29
SEQ ID NO: 29
SEQ ID NO: 30
SEQ ID NO: 30
SEQ ID NO: 25
SEQ ID NO: 25
SEQ ID NO: 26
SEQ ID NO: 26
SEQ ID NO: 27
SEQ ID NO: 27
SEQ ID NO: 21
SEQ ID NO: 21
SEQ ID NO: 22
SEQ ID NO: 22
SEQ ID NO: 23
SEQ ID NO: 23
SEQ ID NO: 37
SEQ ID NO: 3
SEQ ID NO: 38
SEQ ID NO: 38
SEQ ID NO: 49
SEQ ID NO: 49
SEQ ID NO: 50
SEQ ID NO: 50
SEQ ID NO: 51
SEQ ID NO: 51
SEQ ID NO: 52
SEQ ID NO: 52
SEQ ID NO: 46
SEQ ID NO: 46
SEQ ID NO: 47
SEQ ID NO: 47
SEQ ID NO: 48
SEQ ID NO: 48
SEQ ID NO: 35
SEQ ID NO: 35
SEQ ID NO: 36
SEQ ID NO: 36
SEQ ID NO: 42
SEQ ID NO: 42
SEQ ID NO: 43
SEQ ID NO: 43
SEQ ID NO: 44
SEQ ID NO: 44
SEQ ID NO: 45
SEQ ID NO: 45
SEQ ID NO: 39
SEQ ID NO: 39
SEQ ID NO: 40
SEQ ID NO: 40
SEQ ID NO: 41
SEQ ID NO: 41
SEQ ID NO: 49
SEQ ID NO: 49
SEQ ID NO: 47
SEQ ID NO: 47
SEQ ID NO: 5
SEQ ID NO: 5
3. (Previously Presented) The pharmaceutical composition according to claim 1, wherein the anti- Claudin18.2 antibody drug conjugate has a structure of general formula (Pc-L-Y-D):
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643
590
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, which corresponds to instant claim 1.
4. (Currently Amended) The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition further comprises a surfactant selected from which is polysorbate (species). Instant specification also teaches the pharmaceutical composition further comprises surfactant, see para. [0116], such as TWEEN-20, see para. [0251].
5. (Previously Presented) The pharmaceutical composition according to claim 4, wherein the surfactant is at a concentration of 0.05 mg/mL to 0.5 mg/mL. Instant specification also teaches the surfactant, e.g., Tween-20 at concentration of 0.2 mg/ml, which is with the claimed range of 0.05 mg/mL to 0.5 mg/mL, see para. [0251].
6. (Previously Presented) The pharmaceutical composition according to claim 1, wherein the composition further comprises a sugar selected from the group consisting of sucrose, mannitol and trehalose. Instant specification also teaches the composition further comprises sucrose at concentration 60 mg/mL, see para. [0251].
7. (Previously Presented) The pharmaceutical composition according to claim 6, wherein the sugar is at a concentration of 20 mg/mL to 100 mg/mL. Instant specification also teaches the composition further comprises sucrose (aka sugar) at concentration 60 mg/mL, see para. [0251].
8. (Previously Presented) The pharmaceutical composition according to claim 1, wherein the anti- Claudin18.2 antibody drug conjugate is at a protein concentration of 1 mg/mL to 100 mg/mL. The instant specification teaches the antibody-drug conjugate is at 10 mg/ml, which is within the claimed range of 1 mg/mg to 100 mg/ml, see para. [0251].
9. (Previously Presented) The pharmaceutical composition according to claim 1, wherein the buffer is at a concentration of 5 mM to 50 mM. The instant specification teaches that the PBS buffer is 50 mM, or 10 mM succinic acid buffer, see para. [0251].
10. (Previously Presented) The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition has a pH of 5.0-6.5. The instant specification teaches that the 10 mM succinic acid buffer is at pH 5.3, which is within the range pH of 5.0-6.5, see para. [0251].
11. (Previously Presented) The pharmaceutical composition according to claim 1, comprising the following components: (a) the anti-Claudin18.2 antibody drug conjugate at a protein concentration of 10 mg/mL to 30 mg/mL, (b) 0.1 mg/mL to 0.2 mg/mL polysorbate, (c) 40 mg/mL to 80 mg/mL sugar, and (d) 10 mM to 30 mM histidine salt buffer; the pharmaceutical composition having a pH of 5.0-5.5.
12. (Original) A pharmaceutical composition, comprising: an anti-Claudin 18.2 antibody drug conjugate at a protein concentration of 20 mg/mL, 0.2 mg/mL polysorbate 80, 40 mg/mL sucrose, and 30 mM histidine-acetate buffer; the pharmaceutical composition having a pH of 5.0 to 5.3;
The anti-Claudin18.2 antibody drug conjugate having a structure of the formula shown below:
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278
581
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17. (Previously Presented) An article of manufacture, comprising a container containing the pharmaceutical composition according to claim 1.
18. (Currently Amended) A method for treating a tumor or cancer comprising administering to a subject an effective amount of the pharmaceutical composition according to claim 1; wherein the tumor or cancer is selected from the group consisting of head and neck squamous cell carcinoma, head and neck cancer, brain cancer, neuroglioma, glioblastoma multiforme, neuroblastoma, central nervous system carcinoma, neuroendocrine tumor, throat cancer, nasopharyngeal cancer, esophageal cancer, thyroid cancer, malignant pleural mesothelioma, lung cancer, breast cancer, liver cancer, hepatoma, hepatobiliary cancer, pancreatic cancer, gastric cancer, gastrointestinal cancer, intestinal cancer, colon cancer, colorectal cancer, kidney cancer, clear cell renal cell carcinoma, ovarian cancer, endometrial cancer, cervical cancer, bladder cancer, prostate cancer, testicular cancer, skin cancer, melanoma, leukemia, lymphoma, bone cancer, chondrosarcoma, myeloma, multiple myeloma, myelodysplastic syndrome, Krukenberg tumor, myeloproliferative tumor, squamous cell carcinoma, Ewing's sarcoma, systemic light chain amyloidosis and Merkel cell carcinoma, which corresponds to instant claims 24, 26.
19. (Previously Presented) The pharmaceutical composition according to claim 1, wherein the anti-Claudin18.2 antibody drug conjugate has a structure of the formula shown below:
20. (Currently Amended) The method of claim 18, wherein the lung cancer is selected from the group consisting of non-small cell lung cancer and small cell lung cancer, which corresponds to instant claim 26, instant application, para. [0040] to [0042].
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant’s arguments, filed April 3, 2026, have been fully considered but have not been found convincing.
Applicant submits that the present application relates to a CLDN18.2 ADC, with a priority date of December 12, 2019, and PCT filing date December 11, 2020. The '075 Application relates to formulations of CLDN 18.2 ADC, having a priority date of September 30, 2020 and PCT filing date of September 30, 2021. As set forth in MPEP 804, if a provisional nonstatutory 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 nonstatutory double patenting rejection in the other application into a nonstatutory double patenting rejection upon issuance of the patent. Since the instant application has an earlier PCT filing date (December 11, 2020) than the '075 application (September 30, 2021), Applicant respectfully requests that the Examiner withdraw the non-statutory double patenting rejection over the '075 Application.
In response, the copending application has been allowed. A terminal disclaimer is needed to overcome this rejection because the claims overlap in scope. The species of antibody-drug conjugate in the instant claims 20, 21 are disclosed in the ‘075 specification (see copending claims 3, 12), and thus the instant claims are not patently distinct from the ‘075 claims. For these reasons, the rejection is maintained.
Claims 1, 4-5, 7-11, 14, 19, 24 and 26-31 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claim 11 of U.S. Patent No. 12,428,478 (17/442,939) in view of WO2019219891 (published November 21, 2019; PTO 892).
Although the conflicting claims are not identical, they are not patentably distinct from each other because the claims differ only in scope. The instant claims limit the drug linker of formula (Pc-LY-D)
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614
810
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177
800
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wherein i) the heavy chain variable region comprises a HCDR1, a HCDR2 and a HCDR3 having sequences set forth in SEQ ID NO: 15, SEQ ID NO: 16 and SEQ ID NO: 17, respectively, and the light chain variable region comprises an LCDR1, an LCDR2 and an LCDR3 having sequences set forth in SEQ ID NO: 18, SEQ ID NO: 19 and SEQ ID NO: 20, respectively; or
ii) the heavy chain variable region comprises an HCDR1, an HCDR2 and an HCDR3 having sequences set forth in SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11, respectively, and the light chain variable region comprises an LCDR1, an LCDR2 and an LCDR3 having sequences set forth in SEQ ID NO: 12, SEQ ID NO: 13 and SEQ ID NO: 14, respectively.
Issued claim 11 recites an antibody-drug conjugate comprising the anti-Claudin 18.2 antibody comprising a heavy chain variable region and a light chain variable region, wherein:
i) the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 as shown in SEQ ID NO: 15, SEQ ID NO: 16 and SEQ ID NO: 17, respectively, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 as shown in SEQ ID NO: 18, SEQ ID NO: 19 and SEQ ID NO: 20, respectively; or
ii) the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 as shown in SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11, respectively, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 as shown in SEQ ID NO: 12, SEQ ID NO: 13 and SEQ ID NO: 14, respectively and a cytotoxic drug (genus).
The issued claimed anti-Claudin 18.2 antibody drug conjugate comprises the same anti-claudin 18.2 antibody as instant claims, see chart below.
17/782980
12,428,478
SEQ ID NO: 15
SYWMH
SYWMH
SEQ ID NO: 16
MIHPNSGSTNYNEKFKG
MIHPNSGSTNYNEKFKGR
SEQ ID NO: 17
LKTGNSFDY
LKTGNSFDY
SEQ ID NO: 18
KSSQSLLNSGNQKNYLT
KSSQSLLNSGNQKNYLT
SEQ ID NO: 19
WASTRES
WASTRES
SEQ ID NO: 20
QNAYTYPFT
QNAYTYPFT
SEQ ID NO: 9
DYGIH
DYGIH
SEQ ID NO: 10
YISRGSSTIYYADTVKG
YISRGSSTIYYADTVKG
SEQ ID NO: 11
GGYDTRNAMDY
GGYDTRNAMDY
SEQ ID NO: 12
KSSQSLLNSGNQKNYLA
KSSQSLLNSGNQKNYLA
SEQ ID NO: 13
GASTRAS
GASTRAS
SEQ ID NO: 14
QNDLYYPLT
QNDLYYPLT
SEQ ID NO: 5
SEQ ID NO: 5
SEQ ID NO: 6
SEQ ID NO: 6
SEQ ID NO: 31
SEQ ID NO: 31
SEQ ID NO: 28
SEQ ID NO: 28
SEQ ID NO: 3
SEQ ID NO: 3
SEQ ID NO: 4
SEQ ID NO: 4
SEQ ID NO: 24
SEQ ID NO: 24
SEQ ID NO: 21
SEQ ID NO: 21
SEQ ID NO: 29
SEQ ID NO: 29
SEQ ID NO: 30
SEQ ID NO: 30
SEQ ID NO: 25
SEQ ID NO: 25
SEQ ID NO: 26
SEQ ID NO: 26
SEQ ID NO: 27
SEQ ID NO: 27
SEQ ID NO: 21
SEQ ID NO: 21
SEQ ID NO: 22
SEQ ID NO: 22
SEQ ID NO: 23
SEQ ID NO: 23
SEQ ID NO: 37
SEQ ID NO: 3
SEQ ID NO: 38
SEQ ID NO: 38
SEQ ID NO: 49
SEQ ID NO: 49
SEQ ID NO: 50
SEQ ID NO: 50
SEQ ID NO: 51
SEQ ID NO: 51
SEQ ID NO: 52
SEQ ID NO: 52
SEQ ID NO: 46
SEQ ID NO: 46
SEQ ID NO: 47
SEQ ID NO: 47
SEQ ID NO: 48
SEQ ID NO: 48
SEQ ID NO: 35
SEQ ID NO: 35
SEQ ID NO: 36
SEQ ID NO: 36
SEQ ID NO: 42
SEQ ID NO: 42
SEQ ID NO: 43
SEQ ID NO: 43
SEQ ID NO: 44
SEQ ID NO: 44
SEQ ID NO: 45
SEQ ID NO: 45
SEQ ID NO: 39
SEQ ID NO: 39
SEQ ID NO: 40
SEQ ID NO: 40
SEQ ID NO: 41
SEQ ID NO: 41
SEQ ID NO: 49
SEQ ID NO: 49
SEQ ID NO: 47
SEQ ID NO: 47
SEQ ID NO: 5
SEQ ID NO: 5
The issued patent does not teach the drug-linker of general formula (Pc-L-D) wherein the Pc-LY-D is
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620
825
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177
800
media_image4.png
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as per claim 1, wherein the linker unit wherein L3 is a tetrapeptide reissue of the sequence set forth in SEQ ID NO: 55 (GGFG) as per claim 15 and wherein the general formula (Pc-L-Y-D) is
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263
705
media_image6.png
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Pc, R1, R2, R5 to R7, m and n are as defined in claim 1 as per claim 19.
However, the WO2019/219891 publication teaches antibody-drug conjugate comprising anti-MUC1 antibody conjugated to a drug-linker structure
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365
794
media_image7.png
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, wherein y is 1 to 10, or 2 to 8, see entire document, p. 31-33, p. 69-70, in particular.
The reference linker comprises –(succinimid-3-yl-N)-CH2-CH2-CH2-CH2-CH2-C(=O)-GGFG-NH-CH2-O-CH2-C(=O)-, which corresponds to instant L1-L2-L3-L4 wherein L1 is the succinimide, L2 is a chemical bond, L3 is tetrapeptide GGFG, L4 is NR5(CR6R7) wherein R5, R6 and R7 are identical and each independently hydrogen, n is 1-10, preferably n is 2-8, the antibody (AB) is connected to linker (L or *), see p. 31, line 5-7, in particular.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filling date of the claimed invention to conjugate any one of the anti-claudin18.2 antibody of
‘478 patent to the exatecan drug linker as taught by the WO2019/219891 publication to arrive at the claimed conjugate with a reasonable expectation of success, e.g., targeting exatecan or DXd to claudin 18.2 expressing cancer to release the drug at the site of cancer.
One of ordinary skill in the art would have been motivated to do so because the WO2019/219891 publication teaches that the antibody-drug conjugate (ADC) is useful for treating various cancer, e.g., liver cancer, colon cancer, head and neck cancer, gastrointestinal cancer, etc., see p. 12, lines 5-14.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant’s arguments, filed April 3, 2026, have been fully considered but have not been found convincing.
Applicant submits claim 1 of the present application clearly defines the CDR sequences of the CLDN18.2 antibody moiety and the specific linker-drug structure. Although the '478 Patent discloses the antibody sequences in the present application, it only relates to naked antibodies, which are completely different from the specific ADCs claimed in the present application. Importantly, the two are distinct in many aspects such as molecular structure, mechanism of action, and biological function. A person skilled in the art would recognize that antibodies and ADCs belong to different modalities, and they are also submitted for clinical trials and approved for marketing in accordance with different requirements. Therefore, Applicant submits that the claimed subject matter is patentably distinct from the '478 Patent. Withdrawal of the double patenting rejection over the '478 Patent is respectfully requested.
In response, contrary to applicant’s assertion that the '478 Patent only relates to naked antibodies, applicant’s attention is directed to claim 11 of the ‘478 patent.
Although the '478 Patent discloses the antibody sequences in the present application, the ‘478 patent does not disclose the drug linker of formula (Pc-L-Y-D) as set forth in claims 1 and 19 wherein L3 is a tetrapeptide residue of the sequence set forth in SQE ID NO: 55 (GGFG) as per claim 14.
However, the WO2019/219891 publication teaches antibody-drug conjugate comprising anti-MUC1 antibody conjugated to a drug-linker structure
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365
794
media_image7.png
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, wherein y is 1 to 10, or 2 to 8, see entire document, p. 31-33, p. 69-70, in particular.
The reference linker comprises –(succinimid-3-yl-N)-CH2-CH2-CH2-CH2-CH2-C(=O)-GGFG-NH-CH2-O-CH2-C(=O)-, which corresponds to instant L1-L2-L3-L4 wherein L1 is the succinimide, L2 is a chemical bond, L3 is tetrapeptide GGFG, L4 is NR5(CR6R7) wherein R5, R6 and R7 are identical and each independently hydrogen, n is 1-10, preferably n is 2-8, the antibody (AB) is connected to linker (L or *), see p. 31, line 5-7, in particular.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filling date of the claimed invention to conjugate any one of the anti-claudin18.2 antibody of
‘478 patent to the exatecan drug linker as taught by the WO2019/219891 publication to arrive at the claimed conjugate with a reasonable expectation of success, e.g., targeting exatecan or DXd to claudin 18.2 expressing cancer to release the drug at the site of cancer.
One of ordinary skill in the art would have been motivated to do so because the WO2019/219891 publication teaches that the antibody-drug conjugate (ADC) is useful for treating various cancer, e.g., liver cancer, colon cancer, head and neck cancer, gastrointestinal cancer, etc., see p. 12, lines 5-14.
For these reasons, the rejection is maintained.
Conclusion
No claim is allowed.
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/PHUONG HUYNH/ Primary Examiner, Art Unit 1641
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