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 16-17 and 22 have been cancelled and claims 15, 18, and 20 have been amended, as requested in the amendment filed on 07/28/2026. Following the amendment, claims 1-15, 18-21, and 22-24 are pending in the instant application.
Claims 10-13 stand as withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventions in the Response filed 09/11/2025, there being no allowable generic or linking claim.
Claims 1-9, 14-15, 18-21, and 23-24 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. Additionally, it is noted that an English translation of the foreign priority document has been provided, and as such the claim to foreign priority has been perfected.
Claims 1-9, 14-15, 18-21, and 23-24 have an effective filing date of June 28, 2019 corresponding to CN201910577909.6.
Claim Objections - Withdrawn
Claim 20 was objected to for a minor informality regarding a typographical error. Claim 20 has been amended to remove the typographical error. As such, the objection to claim 20 is withdrawn.
Claim Rejections - 35 USC § 112 - Withdrawn
Claims 15, 18, and 23-24 were rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, regarding scope of enablement. Independent claims 15 and 18 have been amended to now require that “the cancer expresses the antigen targeted by the antibody”, and in view of the amendment claims 15, 18, and 23-24 are considered to be enabled. The rejection of claims 15, 18, and 23-24 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, regarding scope of enablement is withdrawn.
Claim Rejections - 35 USC § 103 - Withdrawn
Claims 1-9, 14-15, 18-21, and 23-24 were rejected under 35 U.S.C. 103 as being unpatentable over CN 104755494A (previously cited on PTO-892; machine translation utilized; herein after referred to as "Masuda") in view of WO 2009/099741 Al (previously cited on PTO-892; herein after referred to as "Cohen"), non-patent literature by Jain et.al. (Pharm. Res., 2015, 32, 3526-3540; previously cited on PTO-892; herein after referred to as "Jain") and non-patent literature by Bryden et.al. (Org. Biomol. Chem., 2018, 16, 1882-1889; previously cited on PTO-892; herein after referred to as "Bryden") as evidenced by US 2009/0041770 Al (previously cited on PTO-892; herein after referred to as "Chamberlain").
Applicant’s arguments, see Pages 18-29 of Remarks, filed 07/28/2026, with respect to the rejections of claim(s) 1-9, 14-15, and 18-21 under 35 U.S.C. 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of WO 2019/236954 A1 (herein after referred to as "Jeffrey"), non-patent literature by Ogitani et. al. (Clinical Cancer Res., 2016, 22(20), OF1-OF12; herein after referred to as “Ogitani”), non-patent literature by Bryden et. al. (Org. Biomol. Chem., 2018, 16, 1882-1889; previously cited on PTO-892; herein after referred to as "Bryden"), and US 2009/0041770 A1 (previously cited on PTO-892; herein after referred to as “Chamberlain”).
Terminal Disclaimer
The terminal disclaimer filed on 07/28/2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of Application No. 18/884,153 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Double Patenting - Withdrawn
Claims 1-9, 14-15, 18-21, and 23-24 were provisionally rejected, and new claims 23-24 are newly provisionally rejected, on the ground of nonstatutory double patenting as being unpatentable over the pertinent claims of the copending Application Nos. listed below in view of CN 104755494 A (machine translation utilized; herein after referred to as "Masuda") and WO 2009/099741 A1 (herein after referred to as "Cohen"), as evidenced by US 2009/0041770 A1 (herein after referred to as “Chamberlain”).
Application No.
Brief Description of the Invention
Pertinent Claims
18293078
An Antibody-Drug Conjugate Generally Comprising a PABC Linker Component, a Topoisomerase Inhibitor, and an Anti-DLL3 Antibody, Method for Treating a Disease, and Pharmaceutical Composition Thereof
10-13, 17-18, 22
18884153
An Antibody-Drug Conjugate Generally Comprising a PABC Linker Component, a Topoisomerase Inhibitor, and an Anti-TROP2 Antibody
1-11
With regard to the rejection over copending Application No. 18/884,153, as noted above a terminal disclaimer has been filed and accepted over the copending application. As such, the rejection of claims 1-9, 14-15, 18-21, and 23-24 over claims 1-11 of copending Application No. 18/884,153 in view of Masuda, Cohen, and Chamberlain is withdrawn.
With regard to the rejection over copending Application No. 18/293,078, it is noted that Applicant’s arguments with regard to the cited prior art references have been deemed persuasive. As such, the rejection of claims 1-9, 14-15, 18-21, and 23-24 over claims 10-13, 17-18, and 22 of copending Application No. 18/293,078 in view of Masuda, Cohen, and Chamberlain is withdrawn.
Claim Rejections - 35 USC § 103 - New
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.
Claims 1-9, 14-15, 18-21, and 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2019/236954 A1 (herein after referred to as "Jeffrey") in view of non-patent literature by Ogitani et. al. (Clinical Cancer Res., 2016, 22(20), OF1-OF12; herein after referred to as “Ogitani”), non-patent literature by Bryden et. al. (Org. Biomol. Chem., 2018, 16, 1882-1889; previously cited on PTO-892; herein after referred to as "Bryden"), and US 2009/0041770 A1 (previously cited on PTO-892; herein after referred to as “Chamberlain”).
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Jeffrey teaches antibody-drug conjugates with camptothecin compounds, including methods of use and preparations thereof (Abstract). Jeffrey teaches that the camptothecin conjugates of the invention are stable in circulation, yet capable of inflicting cell death once free drug is released from a conjugate in the vicinity or within tumor cells (Paragraph 0004); in one embodiment a camptothecin conjugate of the invention has a formula: L-(Q-D)p, or a salt thereof, wherein L is a ligand unit, subscript p is an integer from 1 to 16, and Q is, generally, a linker, and D is a drug unit that can be selected from a group comprising CPT4 (Paragraph 0005, Pages 2-4).
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In a group of embodiments, camptothecin conjugates comprising a drug unit of CPT4 are represented by the formulae reproduced below (see Pages 35-36):
Jeffrey teaches that the ligand unit L is a targeting agent that specifically binds a target moiety that acts to target the camptothecin of the conjugates to the particular target cell population with which the ligand unit interacts, wherein the ligan unit includes, for example, antibodies (Paragraph 0163) wherein antibodies useful in the invention include monoclonal antibodies are
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to a particular antigenic determinant (e.g., a cancer cell antigen, a viral antigen, a microbial antigen, a protein, a peptide, a carbohydrate, a chemical, nucleic acid, or fragments thereof) (Paragraph 0175). In specific embodiments, a known antibody for the treatment of cancer is used (Paragraph 0184). With regard to linker unit Q as shown in the CPT4 conjugates above, Z is a stretcher unit, A is a bond or connector unit, B is a branching unit, S* is a partitioning agent, RL is a releasable linker (e.g., glucuronide unit or non-glucuronide unit), and Y is a spacer unit (see Paragraphs 0196-0204). Stretcher unit Z acts to connect the ligand unit to the remainder of the conjugate and, prior to attachment to a ligand unit (i.e. a stretcher unit precursor, Z'), has a functional group that can form a bond with a functional group of a targeting ligand (Paragraph 0205). An exemplary stretcher unit of the invention is of the formula shown below, wherein the bond at the left side of the structure connects to L and the bond at the right side of the structure connects to B, A, or S* (Paragraph 0215):
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In some embodiments, RL units contain a PAB moiety, and have the formula below:
wherein the wavy line marked with ** indicates the site of attachment to D; and the wavy
line marked with * indicates the point of attachment to additional linker components of Q (Paragraph 0281). In some embodiments, RL comprises a heterocyclic "self-immolating moiety"
of Formulas I, II or III bound to the drug and incorporates an amide group that upon hydrolysis by an intracellular protease initiates a reaction that ultimately cleaves the self-immolative
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moiety from the drug such that the drug is released from the conjugate in an active form; the linker moiety further comprises a peptide sequence adjacent to the self-immolative moiety that is a substrate for an intracellular enzyme, for example an intracellular protease such as a cathepsin (e.g., cathepsin B), that cleaves the peptide at the amide bond shared with the self-immolative moiety (Paragraph 0282-0287):
The spacer unit S can be a functional group to facilitate attachment of RL to the Camptothecin, or it can provide additional structural components to further facilitate release of the camptothecin
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from the remainder of the conjugate (e.g., a methylene carbamate unit) (Paragraph 0317). In those embodiments to further facilitate release of the camptothecin as free drug, exemplary spacer units are represented by the formulae reproduced below (Paragraphs 0318-0320):
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wherein in further embodiments spacer units that are methylene carbamate units are represented by the formulae reproduced below (Paragraphs 0321-0323):
It is specifically noted that Jeffrey defines “free drug” as referring to a drug as it exists once released from the drug-linker moiety, and in some embodiments, the free drug includes a fragment of the releasable linker or spacer unit (Y) group; free drug, which includes a fragment of the releasable linker or spacer unit (Y), are released from the remainder of the drug-linker moiety via cleavage of the releasable linker or released via the cleavage of a bond in the spacer unit (Y) group and is biologically active after release (Paragraph 0195). Jeffrey teaches scheme 1b, reproduced below, which depicts a mechanism of free drug release from a Camptothecin attached to a methylene carbamate unit in a camptothecin conjugate having a self-immolative moiety. In that scheme, T* is a heteroatom from the hydroxyl or primary or secondary amine of a camptothecin compound that is incorporated into the methylene carbamate unit (Paragraph 0324, see Pages 92-93):
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From the above, one of ordinary skill in the art would recognize that when the methylene carbamate unit comprises -N(CH2CH2S(O)sCH3)-CH2-O-CH2-C(O), which is attached to CPT4 via the amine group, the bolded oxygen atom assumes the T* position in the scheme above, such the free drug released corresponds to CPT4(via NH)C(O)-CH2OH, corresponding to
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the structure below:
Jeffrey further teaches that subscript p represents the number of drug linker moieties on a ligand unit of an individual camptothecin conjugate and is an integer preferably ranging from 1 to 16, 1 to 12, 1 to 10, or 1 to 8 (Paragraph 0325); in some embodiments, conjugation will be via the interchain disulfides and there will from 1 to about 8 camptothecin linker compound molecules conjugated to a targeting agent that becomes a ligand unit and in some embodiments conjugation will be via an introduced cysteine residue as well as interchain disulfides and there will be from 1 to 10 or 1 to 12 or 1 to 14 or 1 to 16 camptothecin linker compound molecules conjugated to a ligand unit (Paragraph 0326). Thus, Jeffrey reads on a camptothecin conjugate of the following structure:
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Furthermore, it is noted that Jeffrey teaches that the camptothecin conjugates of the invention are useful for inhibiting the multiplication of a tumor cell or cancer cell, causing apoptosis in a tumor or cancer cell, or for treating a cancer in a patient (Paragraph 0333). In one embodiment, the ligand unit of a camptothecin conjugate binds to or associates with a cancer-cell or a tumor-cell-associated antigen, and the camptothecin conjugate is taken up (internalized) inside the tumor cell or cancer cell through receptor-mediated endocytosis or other internalization mechanism, further wherein, in some embodiments, the antigen is attached to a tumor cell or cancer cell or is an extracellular matrix protein associated with the tumor cell or cancer cell (Id.). Cancers that are intended to be treated with camptothecin conjugates of the invention include those listed in Paragraph 0338, which include, for example, breast cancer, pancreatic cancer, stomach cancer, lung cancer, and bladder cancer. Jeffrey further teaches that the invention provides pharmaceutical compositions comprising the camptothecin conjugates of the invention and at least one pharmaceutically acceptable carrier; the pharmaceutical composition is in any form that allows the compound to be administered to a patient for treatment of a disorder associated with expression of the antigen to which the ligand unit binds (Paragraph 0352).
However, while it is noted that Jeffrey suggests the incorporation of cleavable peptides for use in combination with a self-immolative unit of Formula I-III above wherein such a unit is attached via an -OH of the lactone rings of the drug units, Jeffrey does not explicitly teach or suggest a linker comprising a PAB-Ala-Val linker unit specifically wherein the linker is attached via the -NH group of the drug unit. Nor does Jeffrey explicitly teach or suggest a ligand unit that is anti-HER2 antibody trastuzumab. These deficiencies are remedied by Ogintani, Bryden, and Chamberlain.
Ogitanti teaches the ADC structure of DS-8201a is shown in Fig. 1A (reproduced below) wherein DS-8201a is a HER2-targeting ADC and is composed of an anti-HER2 antibody and a derivative of DX-8951 (DXd), a topoisomerase I inhibitor, which are bound together by a maleimide glycyn-glycyn-phenylalanyn-glycyn (GGFG) peptide linker (Page OF3, Column 2, Structure of DS-8201a).
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The linker payload is conjugated with the antibody via the cysteine residues after the interchain disulfide bounds are reduced with a reducing agent, tris (2-carboxyethyl) phosphine hydrochloride (TCEP HCl), and as the tetrapeptide is decomposed by lysosomal enzymes such as cathepsins B and L which are highly expressed in tumor cells, it is supposed that DS-8201a is cleaved by lysosomal enzymes and releases DXd, which attacks target molecules specifically in tumor cells after it binds to HER2 receptors and is internalized in tumor cells; by using RPC, the DAR of DS-8201a was determined as approximately 8, which is the theoretical maximum drug loading number for conventional interchain cysteine conjugation (Id.). Furthermore, the authors confirmed that DXd is more potent in inhibitory activity in topoisomerase I than SN-38 as well as DX-8951f, as measured by a topoisomerase I–mediated DNA relaxation assay (Fig. 1C) (OF4, Column 1, First Partial Paragraph). The inhibitory activity of DS-8201a against cancer cell growth was compared with an anti-HER2 Ab and control IgG–ADC–conjugated with DXd against various human cancer cell lines (KPL-4, NCI-N87, SK-BR-3, and MDA-MB-468; HER2 expressing human breast cancer, HER2 expressing human gastric adenocarcinoma, HER2 expressing human breast cancer, and HER2 negative triple negative breast cancer cell lines, respectively) in vitro; results indicate that the cell growth–inhibitory activity of DS-8201a was remarkably enhanced by drug conjugation to the anti HER2 Ab, and also that DS-8201a shows target-specific growth inhibition against HER2-positive cell lines (OF4, Column 1, First Full Paragraph). Additionally, in vivo antitumor activity of DS-8201a was evaluated in a HER2-positive NCI-N87 xenograft model (i.e., HER2 positive gastric cancer), wherein DS-8201a induced tumor growth inhibition in a dose-dependent manner and tumor regression with a single dosing at more than 1 mg/kg without inducing any abnormalities in the general condition or body weight changes of the mice; it is suggested that the in vivo efficacy of DS-8201a depends on its HER2 binding, as no inhibition of tumor growth was seen for the control-IgG ADC (OF4, Column 2, First Paragraph). It is specifically noted that anti-HER2 Ab was a human monoclonal IgG1 produced with reference to the same amino acid sequence as trastuzumab (OF2, Column 2, First Paragraph).
Bryden teaches four novel HER2-targeting, cathepsin B-sensitive antibody-drug conjugates bearing a monomethylauristatin E (MMAE) cytotoxic payload, constructed via the conjugation of cleavable linkers to trastuzumab using a site-specific bioconjugation methodology; the linkers vary by both cleavable trigger motif and hydrophilicity wherein they contain one of two cathepsin B sensitive dipeptides (Val-Cit and Val-Ala), and engendered with either hydrophilic or hydrophobic character via application of a PEG12 spacer (Abstract). Both Val-Ala and Val-Cit are effective enzymatic triggers (cathepsin B sensitive), with the increased hydrophobicity of the Val-Ala offering more facile chemical manipulation, but restricting the drug-antibody ratio (DAR) obtained during bioconjugation; PEGylation augments linker hydrophilicity, allowing for the masking of the challenges of the Val-Ala trigger pair and also facilitating bioconjugation (Page 1886, Column 2, Conclusions). The broad applicability of the linkers developed in this work, in combination with the frequency of cathepsin B overexpression in neoplastic disease states means that these linkers also offer potential for the development of other ADCs exploiting novel antibodies and disease targets (Page 1887, Column 1, First Full Paragraph). Thus, Bryden demonstrates that both Val-Cit and Val-Ala are cathepsin B cleavable, and both are useful as protease-sensitive cleavable linkers for ADCs. While Val-Ala presents challenges regarding DAR, which can be addressed by increasing hydrophilic character of the linker, it is noted that in all cases, ADCs which comprise each of the four linkers all demonstrated excellent cytotoxicity against the target SK-BR-3 cell line analogous with that of the positive control T-DM1, and no cytotoxicity on the T-47D cell line, confirming a lack of cytotoxic action against HER2 minimally-expressing cell lines; while significant differences were observed between the ADCs and the TTZ control, similar efficacy between all synthesized ADCs was observed wherein both ADCs comprising the Val-Ala and Val-Cit (non-PEGylated) linkers engender cytotoxic action equivalent to T-DM1 despite their significant DAR differences which suggests that Val-Ala may be a more effective drug-release trigger (Page 1885, Column 2, Second Paragraph; Figure 6).
Chamberlain is relied upon solely for its teaching of the antibody sequences corresponding to anti-HER antibody trastuzumab. Chamberlain discloses SEQ ID Nos. 11 and 12, corresponding to the heavy and light chains of trastuzumab, respectively (see Figure 22). It is specifically noted that Chamberlain SEQ ID NOs: 11 and 12 are 100% matches to instantly claimed SEQ ID NOs: 6 and 5, respectively.
In the test of whether it is “obvious to try” there must be:
(1) a finding in the art at the time of filing of the invention that there had been a recognized problem or need in the art;
(2) a finding that there had been a finite number of identified, predictable potential solutions to the recognized need or problem;
(3) a finding that one of ordinary skill in the art could have pursued the known potential solutions with a reasonable expectation of success.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the camptothecin conjugates taught by Jeffrey such that the conjugates further comprise a Val-Ala-PABC unit in the linker (i.e., corresponding to RL) wherein the linker is conjugated to the camptothecin CPT4 via the -NH group, and wherein said conjugates further comprise anti-HER2 antibody trastuzumab, wherein the conjugates have the structure below:
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corresponding to the structure of instant claim 1, wherein Ab is trastuzumab, D is a cytotoxic drug (e.g., camptothecin CPT4 of Jeffrey, DXd of Ogitani), m is 2-8, the structure of L1 is formula III wherein (L)p is -Val-Ala- and R1 is a C2 alkyl substituted by (C1 alkyl)-S(O)2-, L2 is -CH2-CH2-CH2-CH2-CH2-, and L3 is succinimide. One would have been motivated to make such modifications because Jeffrey teaches camptothecin conjugates that are serum stable and capable of inflicting cell death once free drug is released, Ogintani suggests anti-HER2 (i.e., trastuzumab) camptothecin conjugates comprising a linker unit cleavable by cathepsin B (i.e., GGFG), wherein the cleavage of the linker yields the free drug corresponding to camptothecin derivative DXd that exerts antitumor effects in HER2-expressing cells, Chamberlain teaches the sequences corresponding to anti-HER2 antibody trastuzumab, and Bryden teaches that Val-Ala-PABC based linkers (i) may be more efficient at releasing drugs from ADCs (i.e., cathepsin B cleavable) and (ii) problems arising from the increased hydrophobicity of including the Val-Ala dipeptide can be overcome by adding hydrophilic groups to increase DAR; notably Jeffrey suggests combining a cleavable peptide with the PAB moiety of the linker, and using spacers with the camptothecin drugs wherein such spacers facilitate conjugation and drug release (e.g., by increasing hydrophilicity, which Bryden suggests in combination with Val-Ala-PAB). One of ordinary skill in the art would have a reasonable expectation of success because Jeffrey suggests higher DAR conjugates (e.g., 1-8 drug linkers per unmodified antibody), combining a cleavable peptide with the PAB moiety of the linker, and using spacers with the camptothecin drugs wherein such spacers facilitate conjugation and drug release (e.g., by increasing hydrophilicity) and wherein the released “free drug” may comprise portions of the spacer molecule; based on exemplary scheme 1b of Jeffrey and the structure rendered obvious above, one of ordinary skill in the art would recognize that the released free drug would correspond to the DXd structure of Ogitani, which would be expected to have improved efficacy relative to the release of free drug CPT4 of Jeffrey.
Double Patenting - New
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 1-15, 18-21, and 22-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 10-13, 17-18, and 22 of copending Application No. 18/293,078 (herein after referred to as “reference application”) in view of WO 2019/236954 A1 (herein after referred to as "Jeffrey"), non-patent literature by Ogitani et. al. (Clinical Cancer Res., 2016, 22(20), OF1-OF12; herein after referred to as “Ogitani”), and US 2009/0041770 A1 (previously cited on PTO-892; herein after referred to as “Chamberlain”).
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Claims 10-13 of the reference application are drawn to antibody-drug conjugate of general formula Ab-(L3-L2-L1-D)m wherein Ab is an anti-DLL antibody, m is to 8, D is a cytotoxic drug:
and further wherein L3, L2, and L1 are defined, reading on the full ADC structures claimed in reference application claim 13, which includes the full ADC structure reproduced below:
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Reference application claim 17 is drawn to a pharmaceutical composition comprising, for example, the ADC according to any one of claims 10-13. Reference application claim 18 is drawn to a use of, for example, the ADC of any one of claims 10-13 and/or the pharmaceutical composition of claim 17 in preparation of a medicament, kit, and/or drug administration device for treatment of a disease related to abnormal expression of DLL3, such as a tumor or cancer. Reference application claim 22 is drawn to a method for diagnosing and/or treating a disease related to abnormal expression of DLL3 comprising administering to a subject in need thereof an ADC of any one of claims 10-13 and/or the pharmaceutical composition of claim 17.
However, it is noted that the reference application does not claim an ADC comprising an anti-HER2 antibody that is trastuzumab. This deficiency is remedied by the combination of Jeffrey, Ogitani, and Chamberlain, whose teachings are provided in detail in the 103 section above.
In the test of whether it is “obvious to try” there must be:
(1) a finding in the art at the time of filing of the invention that there had been a recognized problem or need in the art;
(2) a finding that there had been a finite number of identified, predictable potential solutions to the recognized need or problem;
(3) a finding that one of ordinary skill in the art could have pursued the known potential solutions with a reasonable expectation of success.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the antibody-drug conjugates claimed by the reference application such that they comprise anti-HER2 antibody trastuzumab, wherein the conjugates have the structure below:
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corresponding to the structure of instant claim 1, wherein Ab is trastuzumab, D is a cytotoxic drug (e.g., camptothecin CPT4 of Jeffrey, DXd of Ogitani), m is 2-8, the structure of L1 is formula III wherein (L)p is -Val-Ala- and R1 is a C2 alkyl substituted by (C1 alkyl)-S(O)2-, L2 is -CH2-CH2-CH2-CH2-CH2-, and L3 is succinimide. One would have been motivated to make such modifications because Jeffrey teaches camptothecin conjugates that are serum stable and capable of inflicting cell death once free drug is released, wherein based on exemplary scheme 1b of Jeffrey and the structure rendered obvious above, one of ordinary skill in the art would recognize that the released free drug would correspond to the DXd structure of Ogitani, which would be expected to have improved efficacy relative to the release of free drug CPT4 of Jeffrey. Furthermore, Ogintani suggests anti-HER2 (i.e., trastuzumab) camptothecin conjugates comprising a linker unit cleavable by cathepsin B (i.e., GGFG), wherein the cleavage of the linker yields the free drug corresponding to camptothecin derivative DXd that exerts antitumor effects in HER2-expressing cells, and Chamberlain teaches the sequences corresponding to anti-HER2 antibody trastuzumab.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
With regard to the new rejection presented above, it is noted that the new combination of prior art references render obvious the instantly elected species of ADC. As such, with regard to Applicant’s arguments regarding data previously presented (see Remarks filed 03/02/2026) and unexpected results, it is specifically noted that the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). Furthermore, the arguments of unexpected results relied upon comparisons to prior art references no longer relied upon (i.e., Masuda), rendering such arguments moot.
Conclusion
Claims 1-15, 18-21, and 22-24 are pending. Claims 10-13 are withdrawn. Claims 1-9, 14-15, 18-21, and 23-24 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
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