Double Patenting
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 .
Claims Status
Claim(s) 1-14 is/are currently pending and presented for examination on the merits.
Claim Objections
Claim(s) 5-14 is/are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claim. See MPEP § 608.01(n). Accordingly, claims 5-14 have not been further treated on the merits.
Claim(s) 1-4 is/are objected to because of the following informalities: For clarity, claim 1 should be amended to read as recited below. Appropriate correction is requested.
“An anti-CLDN-18.2 antibody-drug conjugate (ADC) or a pharmaceutically active salt thereof, wherein the ADC formula comprises Formula (I-1):
Ab-(L-D)m, wherein:
L is a linker unit;
D is a cytotoxic small drug molecule;
m represents…”
Claim Rejections - 35 USC § 112(b)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
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.
Claim(s) 1-4 is/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.
Claim(s) 1-4, recite the phrase "preferably 2-7, and more preferably 2-5" in line 8 of claim 1 rendering the claims indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173. It is unclear if the preferred limitation(s) are required limitation(s) or merely provided as an example. For the purposes of compact prosecution, the preferred limitations are not considered part of the claimed invention. This rejection may be overcome by amending claim(s) 1 to remove preferred limitations. Claim(s) 2-4 can overcome this rejection by amending claim(s) 1 as recited above.
Claim(s) 1-4, recite(s) “as shown in SEQ ID NO:…” in lines (I)-(V) in claim 1, rendering the claim(s) indefinite. Specifically, it is unclear if the phrase “as shown in” means (1) there must be a 100% sequence identity to the recited sequence(s); (2) a partial sequence match (e.g., a shorter section of the sequence(s) recited); or (3) something else. For the purposes of compact prosecution, the phrase will be considered to mean “comprising” (e.g., requiring a 100% sequence identity match to sequence(s) recited). This rejection may be overcome by amending claim(s) 1 as recited above or to otherwise clearly recite the limitation(s) of the instant invention. Claim(s) 2-4 can overcome this rejection by amending claim(s) 1 as recited above.
Regarding claim(s) 2-4, the phrase "preferably" in line 3 of claim 2, and line 7 of claim 3 renders the claims indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173. It is unclear if the preferred limitation(s) are required limitation(s) or merely provided as an example. For the purposes of compact prosecution, the preferred limitations are not considered part of the claimed invention. This rejection may be overcome by amending claim(s) 2 and 3 to remove preferred limitations. Claim(s) 4 can overcome this rejection by amending claim(s) 2 and 3 as recited above.
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.
Claim(s) 1-3 is/are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim(s) 17-23 of copending Application No. 18/016,279 (reference application; hereinafter “A279”), in view of WO2016/166122 A1 (hereinafter “WO122”). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding instant claim(s) 1-3, A279 claims 17-23 teach an anti-CLDN-18.2 antibody or antigen binding fragment thereof comprising an HCDR1-3 and LCDR1-3 with 100% sequence identity to the instant claimed anti-CLDN-18.2 HCDR1-3 and LCDR1-3 sequences (see sequence alignments below for matching 6 CDR sets between the instant application and A279).
Alignment of instant anti-CLDN-18.2 antibody HCDR1-3 and LCDR1-3 (SEQ ID NOs: 1, 72, 73, 7-9, respectively) with the A279 anti-CLDN18.2 antibody of claim 17 line “(XIV)” (SEQ ID NOs: 1, 72, 73, 7-9, respectively):
CLUSTAL O(1.2.4) multiple sequence alignment
Instant_1x72x73xxxxx7x8x9 NFGMHxYISSGSGTIYYADSVKGxAYYGNAFSFxxxxxKSSQSLLNSGNQKNYLTxWAST 60
A279_1x72x73xxxxx7x8x9 NFGMHxYISSGSGTIYYADSVKGxAYYGNAFSFxxxxxKSSQSLLNSGNQKNYLTxWAST 60
************************************************************
Instant_1x72x73xxxxx7x8x9 RESxQNVYSYPLT 73
A279_1x72x73xxxxx7x8x9 RESxQNVYSYPLT 73
*************
Alignment of instant anti-CLDN-18.2 antibody HCDR1-3 and LCDR1-3 (SEQ ID NOs: 1, 72, 3, 7-9, respectively) with the A279 anti-CLDN18.2 antibody of claim 17 line “(XV)” (SEQ ID NOs: 1, 72, 3, 7-9, respectively):
CLUSTAL O(1.2.4) multiple sequence alignment
Instant_1x72x3xxxxx7x8x9 NFGMHxYISSGSGTIYYADSVKGxAYYGNGFSFxxxxxKSSQSLLNSGNQKNYLTxWAST 60
A279_1x72x3xxxxx7x8x9 NFGMHxYISSGSGTIYYADSVKGxAYYGNGFSFxxxxxKSSQSLLNSGNQKNYLTxWAST 60
************************************************************
Instant_1x72x3xxxxx7x8x9 RESxQNVYSYPLT 73
A279_1x72x3xxxxx7x8x9 RESxQNVYSYPLT 73
*************
Alignment of instant anti-CLDN-18.2 antibody HCDR1-3 and LCDR1-3 (SEQ ID NOs: 1, 41, 3, 7-9, respectively) with the A279 anti-CLDN18.2 antibody of claim 17 line “(XIII)” (SEQ ID NOs: 1, 41, 3, 7-9, respectively):
CLUSTAL O(1.2.4) multiple sequence alignment
Instant_1x41x3xxxxx7x8x9 NFGMHxSISSGSGTIYYADSVKGxAYYGNGFSFxxxxxKSSQSLLNSGNQKNYLTxWAST 60
A279_1x41x3xxxxx7x8x9 NFGMHxSISSGSGTIYYADSVKGxAYYGNGFSFxxxxxKSSQSLLNSGNQKNYLTxWAST 60
************************************************************
Instant_1x41x3xxxxx7x8x9 RESxQNVYSYPLT 73
A279_1x41x3xxxxx7x8x9 RESxQNVYSYPLT 73
*************
Alignment of instant anti-CLDN-18.2 antibody HCDR1-3 and LCDR1-3 (SEQ ID NOs: 10, 40, 12, 13-15, respectively) with the A279 anti-CLDN18.2 antibody of claim 17 line “(XII)” (SEQ ID NOs: 10, 40, 12, 13-15, respectively):
CLUSTAL O(1.2.4) multiple sequence alignment
Instant_10x40x12xxxxx13x14x15 NYGMNxWINTYTGESTYADGFTGxTLGYGNSLAYxxxxxKSSQSLLNSGNQRNYLTxWAS 60
A279_10x40x12xxxxx13x14x15 NYGMNxWINTYTGESTYADGFTGxTLGYGNSLAYxxxxxKSSQSLLNSGNQRNYLTxWAS 60
************************************************************
Instant_10x40x12xxxxx13x14x15 TRESxQNNYFYPFT 74
A279_10x40x12xxxxx13x14x15 TRESxQNNYFYPFT 74
**************
Alignment of instant anti-CLDN-18.2 antibody HCDR1-3 and LCDR1-3 (SEQ ID NOs: 28, 74, 30, 13-15, respectively) with the A279 anti-CLDN18.2 antibody of claim 17 line “(XVI)” (SEQ ID NOs: 28, 74, 30, 13-15, respectively):
CLUSTAL O(1.2.4) multiple sequence alignment
Instant_28x74x30xxxxx13x14x15 SYGMSxTISGGDSYTYYPDSVKGxSYNGNSLPYxxxxxKSSQSLLNSGNQRNYLTxWAST 60
A279_28x74x30xxxxx13x14x15 SYGMSxTISGGDSYTYYPDSVKGxSYNGNSLPYxxxxxKSSQSLLNSGNQRNYLTxWAST 60
************************************************************
Instant_28x74x30xxxxx13x14x15 RESxQNNYFYPFT 73
A279_28x74x30xxxxx13x14x15 RESxQNNYFYPFT 73
*************
Alignment of instant anti-CLDN-18.2 antibody HCDR1-3 and LCDR1-3 (SEQ ID NOs: 28, 74, 75, 13-15, respectively) with the A279 anti-CLDN18.2 antibody of claim 17 line “(XVII)” (SEQ ID NOs: 28, 74, 75, 13-15, respectively):
CLUSTAL O(1.2.4) multiple sequence alignment
Instant_28x74x75xxxxx13x14x15 SYGMSxTISGGDSYTYYPDSVKGxSYNANSLPYxxxxxKSSQSLLNSGNQRNYLTxWAST 60
A279_28x74x75xxxxx13x14x15 SYGMSxTISGGDSYTYYPDSVKGxSYNANSLPYxxxxxKSSQSLLNSGNQRNYLTxWAST 60
************************************************************
Instant_28x74x75xxxxx13x14x15 RESxQNNYFYPFT 73
A279_28x74x75xxxxx13x14x15 RESxQNNYFYPFT 73
*************
A279 does not expressly teach an ADC comprising (a) a valine-citrulline linker and (b) a cytotoxic the cytotoxic drug MMAE.
Regarding instant claims 1-3, WO122 teaches anti-CLDN-18.2 ADCs comprising an anti-CLND-18.2 antibody, a linker, and cytotoxic drug [e.g., title, abstract; fig. 1]. WO122 further teaches that anti-CLND18.2 ADCs are suitable for ADC development and conjugation of anti-CLDN-18.2 antibodies MMAE have been successful using valine-citrulline linkers [e.g., pg. 4, ¶ 1].
It would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to combine the anti-CLDN-18.2 antibodies as taught by A279, with the anti-CLDN-18.2 ADC comprising a valine-citrulline linker and MMAE taught by WO122, to arrive at the instant-claimed anti-CLDN-18.2 ADCs. A PHOSITA would have been motivated to combine the anti-CLDN-18.2 antibodies as taught by A279, with the anti-CLDN-18.2 ADC comprising a valine-citrulline linker and MMAE taught by WO122, because A279 teaches anti-CLDN-18.2 antibodies, and WO122 teaches that anti-CLDN-18.2 ADCs comprising MMAE cytotoxic drug and valine-citrulline linker result in dose-dependent tumor growth inhibition, and even complete regression of early and advance tumors, and is a effective cancer therapy [e.g., title, abstract; pg. 4, ¶ 1]. There would have been a reasonable expectation of success for a PHOSITA to combine the anti-CLDN-18.2 antibodies as taught by A279, with the anti-CLDN-18.2 ADC comprising a valine-citrulline linker and MMAE taught by WO122, because A279 teaches anti-CLDN-18.2 antibodies, and WO122 teaches anti-CLDN18.2 ADCs comprising a valine-citrulline linker and MMAE are effective anti-cancer therapeutics. This rationale aligns with the principle of applying a known technique to a known method to yield predictable results, supporting a conclusion of obviousness (see MPEP § 2143). Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Free From the Prior Art
During the course of examination, the anti-CLDN-18.2 antibody drug conjugate (ADC) and/or antigen binding fragment thereof comprising any one of the HCDR1-3 and LCDR1-3 sets (see summary table below for details), were found to nonobvious over the prior art. Briefly, a sequence search of the prior art returned no 100% sequence identity matches to any of the instant claimed HCDR1-3 sets, and therefore cannot return a 100% matches to the instant claimed HCDR1-3 and LCDR1-3 sets (see closest prior art alignments below).
PNG
media_image1.png
200
400
media_image1.png
Greyscale
Alignment of anti-CLDN-18.2 ADC HCDR1-3 (SEQ ID NO: 1, 72, 73) with WO2011016238-A1 (Mouse anti-A beta monoclonal antibody VH sequence, SEQ 2366):
PNG
media_image2.png
213
557
media_image2.png
Greyscale
Alignment of anti-CLDN-18.2 ADC HCDR1-3 (SEQ ID NO: 1, 72, 3) with WO2011016238-A1 (WO2011016238-A1):
PNG
media_image3.png
219
563
media_image3.png
Greyscale
Alignment of anti-CLDN-18.2 ADC HCDR1-3 (SEQ ID NO: 1, 41, 3) with WO2011016238-A1 (Mouse anti-A beta monoclonal antibody VH sequence, SEQ 2366):
PNG
media_image4.png
211
560
media_image4.png
Greyscale
Alignment of anti-CLDN-18.2 ADC HCDR1-3 (SEQ ID NO: 10, 40, 12) with WO2024098066-A1 (WO2024098066-A1):
PNG
media_image5.png
214
568
media_image5.png
Greyscale
Alignment of anti-CLDN-18.2 ADC HCDR1-3 (SEQ ID NO: 28, 74, 30) with US2005158829-A1 (ScFv-2-1G3-Fc-ScFv-1-1F11 fusion protein SEQ ID NO:51):
PNG
media_image6.png
367
564
media_image6.png
Greyscale
Alignment of anti-CLDN-18.2 ADC HCDR1-3 (SEQ ID NO: 28, 74, 75) with WO2012117067-A1 (WO2012117067-A1):
PNG
media_image7.png
134
554
media_image7.png
Greyscale
Conclusion
No claims are currently allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY M CHATTIN whose telephone number is (571)270-0646. The examiner can normally be reached T-F 0600-1600 PST.
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/AMY M. CHATTIN/Examiner, Art Unit 1643
/GARY B NICKOL/Primary Examiner, Art Unit 1643
Prosecution Insights