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 .
Claims 45 and 47 have been canceled. Claims 1-4, 16,18, 21, 24, 42, 43, 44,and 46, have been amended. Claims 53-61 have been added. Claims 1-5, 10, 12, 13, 15-18, 20, 21, 23, 24, 42-44, 46, 50, 51 and 53-61 are pending and under consideration.
Claim 60 is objected to because of the following informalities: Claim 60 fails to conform to the sequence rules. Both of Gly-Phe-Leu-Gly and Ala-Leu-Ala-Leu are not labeled with the sequence identifiers of SEQ ID NO: 5 and 6, respectively.
Appropriate correction is required.
It is noted that “genetically encoded” amino acids of claims 16, 54 and 56 are interpreted as “unnatural amino acids” because in fact, they are not “genetically encoded” in the context of the instant claims. Genetically encoded ammino acids of claim 16, 54 and 56 require the engineering of a cell to express a polynucleotide having an amber codon, which is not present in nature. Culture of the recombinant cell in the presence of an amber t-RNA modified to carry an artificial structure, such as a tetrazine, results in the incorporation of the artificial structure in the protein. (Seitchik et al, Journal of the American chemical Society, 2012, Vol. 134, pp. 2898-2901, see page 2899, column 1, line 9 o column 2, line 19). In the instant invention, the unnatural amino acids are part of a linker which was synthesized rather than recombinantly expressed as part of a protein. Further, the resulting synthetically made linker would be the same as a linker derived from recombinant expression in a cell engineered to express the amber codon and cultured in the presence of the artificial amber t-RNA bearing the unnatural structure.
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 43 and 53 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.
(A)Applicant has amended claim 43 to place the conjunction “and” between the third listed species and prior to the remaining two species:
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. It is unclear if the selection of (L1)a and (L2)b requires the selection of both of
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.
as a single specie.
(B)The recitation of “carbonyl derived group” in claim 53 lacks specific antecedent basis in claim 1.
The rejection of claim 18 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement and the enablement requirement is withdrawn in light of applicant’s amendment.
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.
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, 2, 3, 4, 5, 10, 17, 18, 20, 21, 23, 24, 42, 44, 50 and 51 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al (WO2018/0753308,reference of the IDS filed 1/3/2023) in view of Sun et al (Bioorganic and Medicinal Chemistry, 2003, Vol. 11, pp. 1761-1768) and Burt et al (WO2014/064423, reference of the IDS filed 4/8/2024).
Liu et al teach the construct of formula Ib (page 2):
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wherein
P is a non-immunogenic polymer, B is H, or a capping group selected from C1-50 alkyl or aryl, , wherein one or more carbons of said alkyl may be replaced with a heteroatom (page 2, lines 15-17). T is a trifunctional small molecule linker moiety and has one, two, or more functional groups that are capable of site- specific conjugation with two different proteins (page 2, lines 7-9); L1 and L2 are bifunctional linkers, “a” and “b” are an integer from 0-10, “y” is an integer from 1-10, which meets the limitations of claim 1 with the exception that L2-A of Liu et al is present in place of the instant “B-Dn”. Liu et al teach that Al and A2 are any two different or same proteins, and at least one of A1 or A2 is a recognition binding moiety such as a single chain antibody (page 2,line 27 to page 3, line 2). Liu et al teach that the non-immunogenic polymer can be polyethylene glycol (page 3, lines 3-4) which meets the limitation of claim 20. Liu et al teach constructs comprising the pegylated multispecific antibodies comprising scFv that have a longer blood half-life than non-pegylated single-chain bispecific antibodies (page 10, lines 13-15). Liu et al teach that the P-moiety can be a linear PEG,
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, wherein B is methyl or other low-molecular weight alkyl (page 10, lines 25-27) which meets the limitations of claim 21. Liu et al teach that “n” is an integer from 10-2300 resulting in a molecular weight of from 10,000 to 40,000 (page 10, lines 24-25) which meets the limitations of claim 23. Liu et al teach that “F” is a terminal functional group for conjugating to the trifunctional small molecule compound (page 10, lines 27-29) which meets the limitations of claim 24 as pertaining to a permanent bond.
Liu et al teach that T can be derived from molecules with any combination of three functional groups, including hydroxyl, carboxyl, thiol and halide, which meet those limitation in claim 2. Liu et al teach that in some embodiments, T is lysine (page 3, line 22) which meets the limitations of claim 3. Liu et al teach that the bifunctional linkers may be:
–(CH2)aC(O)NR1(CH2)b- (page 12, line 28), which meets the limitation of the first listed linker in claim 42, wherein X is C(=O) and Y is NR1;
-(CH2)aO(CH2CH2O)c-(page 12, line 28), which meets the limitation of the second listed linker in claim 42, wherein “b” is 0, and X and Y are null;
-(CH2)aheterocycle- (page 12, line 28) which meets the limitation of the third listed linker in claim 42;
-(CH2)aC(O)- (page 12, line 28) which meets the limitation of the fourth listed linker in claim 42, wherein X is C(=O); and
-(CH2)aNR1-(page 12, line 29) which meets the limitation of the fifth listed linker in claim 42, wherein X is null and Y is NR1,
and wherein a, b and c are from 0-25.
Liu et al teach the functional groups that form linkages within (L1)a or (L2)b or between (L1)a and A1 or between (L2)b and A2 can be selected from the group consisting of thiol, maleimide, 2-pyridyldithio variant, aromatic sulfone or vinyl sulfone, acrylate, bromo or iodo acetamide, azide, alkyne, dibenzocyclooctyl (DBCO), carbonyl, 2-amino-benzaldehyde or 2-amino-acetophenone group, hydrazide, oxime, potassium acyltrifluoroborate, O-carbamoylhydroxylamine, trans- cyclooctene, tetrazine, or triarylphosphine (page 3, lines 12-18) which meet the same limitation in claim 4.
Liu et al teach pharmaceutical formulations comprising the antibody constructs and a pharmaceutically acceptable carrier (page 4, lines 1-2) which meets the limitations of claim 50. Liu et al teach the treatment of oncological diseases including carcinomas of the gastrointestinal tract, colon, stomach, pulmonary tract, lung, breast, ovary, prostate, uterus, endometrium, cervix, urinary bladder, or kidney (page 20, lines 23-33) which meets the limitation of claim 51.
Liu et al do not teach the compound of formula Ib wherein A1 or A2 is replaced by a branched linker “B” wherein each branch has a cleavable bond, wherein cleavage releases D or its derivative; wherein each of D is independently a cytotoxic peptide, and “N” is an integer from 1-25.
Sun et al teach that the use of mAb-drug conjugates targeted at tumor associated antigens have improved efficacy and reduced systemic toxicity doe to the high specificity of the antibody (page 1761, bridging sentence between the first and second columns). Sun et al teach that scFv exhibit improved tumor penetration relative to whole antibodies (page 1761, second column, lines 12-15). Sun et al teach that the small size of the scFv limits the possible number of sites for drug conjugation (page 1761, second column, lines 8-10 of the bottom paragraph). Sun et al teach that in order to address this problem, a linker unit conjugated to one scFv is in which multiple drug units may be attached would overcome this problem (page 1761, second column, lines 10-13). Sun et al teach that doubly branched linkers that a carry two drug molecules onto one site of a moAb have proven useful for increasing the molar ratio of the drug/antibody (page 1761, second column, lines 12-15).
Burt et al teach a preferred conjugate of Formula I’ having the structure:
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wherein “D” is a maytansine or an auristatin (page 39).
Burt et al teach that it was surprisingly found that compounds of formula I’ have improved activity compared with corresponding conjugates with the same number of “D”, drug moieties attached to the antibody without a branching linker (page 40, bottom paragraph). Burt et al teach a pharmaceutical composition comprising the conjugate of formula I’ with a pharmaceutically acceptable carrier, and a method for the treatment of a patient with cancer comprising the administration of a pharmaceutically effective amount of such a conjugate or composition to the patient (page 40, middle paragraph). The compound of formula I’ of Burt et al meets the limitations of claim 1 wherein B is a branched linker comprising an amino acid sequence linked to a self-immolating spacer, wherein cleavage of the amino acid sequence by an enzyme triggers the self-immolating mechanism to release D wherein “D” is a maytansinoid or an auristatin which meets the limitations of “a cytotoxic small molecule” or “peptide” in claim 1, the microtubule inhibitor in claim 17, the requirement for drug release in claim 44.
Burt et al teach that the auristatin includes monomethyl, auristatins E and F (page 3, lines 15-17), which meets the limitation of MAE and MMAF in claim 18.
It would have been prima facie obvious at the time of the effective filing date to substitute
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for -A1 or -A2 in formula Ib
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of Liu et al, wherein the above structure is joined to (L1)a or (L2)b of Formula Ib at the arrow. One of skill in the art would have been motivated to do so by the teachings of Sun et al regarding the use of mAb-drug conjugates over to improve efficacy in targeting tumor associated antigens; that doubly branched linkers that carry two drug molecules onto one site of a moAb have proven useful for increasing the molar ratio of the drug/antibody and that this techniques is especially useful for scFv which are desirable due to their small size and ability to penetrate tumors; and the teachings of Burt et al regarding compounds of formula I’ which have improved activity relative to corresponding conjugates with the same number of “D”, drug moieties attached to the antibody without a branching linker (page 40, bottom paragraph).
The rejection of claims 1-5, 10, 15-18, 20, 21, 23, 24, 42, 44, 50 and 51 under 35 U.S.C. 103 as being unpatentable over Liu et al, Sun et al and Burt et al as applied to claims 1-5, 10, 17, 18, 20, 21, 23, 24, 42, 44, 50 and 51 above, and further in view of Hallam et al (Molecular Pharmaceutics, 2015, Vol. 12, pp. 1848-1862) is maintained for reasons of record.
Claim 15 requires that the two binding domains of the bispecific single chain antibody are linked via a linker comprising a cysteine or an unnatural amino acid for site-specific conjugation of the antibody to L1
Claim 16 requires, in part, that the unnatural amino acid is p-acetyl phenyl alanine or p-azido phenylalanine.
The combined teachings of Liu et al, Sun et al and Burt et al render obvious the limitations of claims 1-5, 10, 17, 18, 20, 21, 23, 24, 42, 44, 50 and 51 for the reasons set forth above. The combined teachings do not address the incorporation of an unnatural amio acid into a bispecific scFv to allow attachment to L1 although Liu et al specifically teaches one example, wherein the two antibodies are respectively an anti-CD3 antibody that binds to a receptor on cytotoxic cell and an anti-CD 19 antibody that binds to a receptor of cancer cell (pages 2-3, bridging sentence). Liu et al teach that said two antibodies can be single chain antibodies (SCA or scFv) (page 3, line 2).
Hallam et al teach the expression of recombinant antibody FA allowing for the site-specific incorporation of an unnatural amino acid and site-specific bio-conjugation, specifically p-AcF and p-AzF (page 1849, Figure 1),. Hallam et al teach that site-specific conjugation produces a homogenous population of antibody conjugates with improved pharmacologic properties relative to conjugates formed through on-site-specific methods (abstract)
It would have been prima facie obvious at the time prior to the effective filing date to provide a bispecific scFv antibody comprising an unnatural amino acid, such as pAcF for linkage to L1 in the formula Ib of Liu et al. One of skill in the art would have been motivated to do so by the teachings of Hallan et al regarding the improvements associated with homogenous populations of antibody conjugates using unnatural amino acids to allow for site-specific conjugation.
The rejection of claims 1-5, 10, 12, 15-18, 20, 21, 23, 24, 42, 44, 50 and 51 under 35 U.S.C. 103 as being unpatentable over Liu et al, Sun et al and Burt et al and Hallam et al as applied to claims 1-5, 10, 15-18, 20, 21, 23, 24, 42, 44, 50 and 51 above, and further in view of Huang et al (Mabs, 2018, Vol. 10, pp. 864-875) and Spiess et al (Molecular Immunology, 2015, Vol. 67, pp. 95-106) is maintained for reasons of record.
Claim 12 requires that the bispecific antibody of claim 10 is an anti-Her2 (ii) X anti-Her2 (IV) antibody.
The combined teachings of Liu et al, Sun et al, Burt et al and Hallam et al render obvious the limitations of claims 1-5, 10, 15-18, 20, 21, 23, 24, 42, 44, 50 and 51 for the reasons set forth above. The combined teachings do not address the requirement of claim 12 wherein the bispecific antibody is an anti-Her2 (ii) X anti-Her2 (iv) antibody, although Liu et al teach that the antibodies of the inventive construct are Double Site-specific PEGylated Bispecific Antibody (DSP-BsAb), which are capable of binding two or more epitopes of the same antigen, and that the two antibodies that bind the same tumor antigen can be scFv,
Huang et al teach afucosylated MBS301 bispecific antibody made with knobs-into-holes technology, wherein the MBS301 comprises a monovalent heavy chain light chain pair specific for Trastuzumab which binds to domain iv of Her2 and a monovalent heavy chain light chain pair specific for pertuzumab which binds to domain ii of Her2 (Figure 1). Huang et al teach that the two arms of MBS301 bind to Her2 domains II and IV simultaneously (page 667). Huang et al teach that MBS301 synergistically inhibited the proliferation of Her2 positive cancer cell lines (page 868 paragraph under the heading, and page 870, first column, top paragraph).
Spiess et al teach bispecific antibody fragments including scFv, such as scFv-CH-CL-scFv (Figure 1, right side of the page, 1st structure, fourth line).
It would have been prima facie obvious at the time prior to the effective filing date to make the bispecific scFv-CH-CL-scFv by recombinant expression thereby including an unnatural amino acid, such as pAcF or pAzF, wherein the first scFv was derived from trastuzumab and bound domain iv of Her2 and the second scFv was derived from pertuzumab and bound the ii domain of Her2, and wherein the unnatural amino acid was used as a conjugation handle for L1. One of skill in the art would have been motivated to do so by the teachings of Liu et on the antibodies of the inventive construct which are capable of binding two or more epitopes of the same antigen, and that the two antibodies that bind the same tumor antigen can be scFv; the teachings of Huang et al on the bispecific antibody MBS301 which incorporates monovalent binding to domain iv of Her2 with monovalent binding to domain ii, wherein binding to both epitopes synergistically inhibits proliferation of Her2 positive cell lines; and the teachings of Hallam et al on the improvements afforded by site-specific conjugation through recombinant incorporation of unnatural amino acids into antibody fragments. One of skill in the art would have been motivated to provide the construct rendered obvious by the combined teachings of Liu et al, Sun et al and Burt et al and Hallam et al wherein in addition to delivery of a cytotoxic agent by antibody targeting via scFv, the scFv itself provided a negative proliferation signal by simultaneous binding to both domain iv and domain ii of Her2 on Her2 positive cells or tumors.
Applicant argues that the construct of Liu et al (formula Ib (page 2))
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pertains only to the attachment of two antibodies as A1 and A2. This has been considered but not found persuasive. Liu et al teach that the multi-specific compound can be further conjugated to one or more effector molecules such as cytotoxic agent, chemotherapeutic agents, drugs growth inhibitory agents, toxins, protein toxins, enzymatically active toxins of bacteria, fungus plant or animal origin (page 29, line 25 to page 31, line 15 of ‘308). Applicant further argues that Liu et al fails to teach the replacement of A1 or A2 with cytotoxic, small molecules connected via a branched linker. This has been considered but not found persuasive, because Sun et a and Burt et al teach the advantages of using branched linkers as stated in the rejection above. Applicant argues that Sun et al and Burt et al provide no teachings regarding the conjugation of the cytotoxic small molecules and “even teach away” from using a branched linker. Applicant states that in Examples 9 and 13 of Burt et al trastuzumab carrying only a single MMAE was superior to a Fab fragment loaded with two MMAE moieties and that based on this, one of skill in the art would conclude that all of the other teachings in Burt et al, namely that “that compounds of formula I’ have improved activity compared with corresponding conjugates with the same number of “D”, drug moieties attached to the antibody without a branching linker” (page 40, bottom paragraph) are negated. This has been considered but not found persuasive. Applicant is comparing the delivery of MMAE cargo to Her2 expressing cell lines by the bivalent trastuzumab to the delivery of MMAE cargo to Her2 expressing cell lines by monovalent Fab. The art teaches that in general, bivalent antibodies capable of mediating receptor dimerization , stimulate the process of endocytosis (Marks et al, WO99/55720, see page 49, line 27 to page 50, line 9). It is not unexpected that the Fab conjugate does not stimulate endocytosis of Her2 relative to the trastuzumab conjugate, and it is therefore not unexpected that the resulting IC50 was not as low as with the trastuzumab conjugate.
Applicant argues that the compounds of formula (Ib) induce effective cytotoxicity against tumor cells with low target antigen expression (example 16), have high internalization rates (example 17), show no recycling or efflux out of target cells after internalization (example 18) and have high tissue specificity (example 19). This has been considered but not found persuasive. Examples 16-19 pertain to compound 111/JY201.
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which is attached to two single chain anti-Her2 antibodies which bind to two different epitopes of Her2 (epitopes II and IV, see Figures 14 and 15). Section 716.02(d) of the M.P.E.P. states that unexpected results must be commensurate in scope with claimed invention. Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.". In the instant claims, compounds of Formula (ib) are claimed:
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which encompass a multitude of linker structures, payloads (“D”) and antibodies. Claims 43, 46, and 59 exemplify a multitude of linkers, none of which appear to be the branch linker in JY201.
Thus, the scope of the claims s not commensurate with the evidence of nonobviousness which is alleged by applicant..
Applicant has also provided “annex 2” with data on the synthesis and evaluation of compounds 112-114. It is noted that the invitro cell growth inhibitory activity of each of compounds 112, 113 and 114 are reported as percent growth inhibition relative to untreated control, which fails to support an unexpected result.
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 44 is provisionally rejected and claims 1-5, 15, 17, 18, 20, 21, 23, 24, 42-44, 50 and 51 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 4, 11, 13, 32, 37, 38, 43, and 44 of copending Application No. 18/992,608(reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘608 application anticipate the instant claims. Claim 1 of ‘608 anticipates claims 1 and 44. Claim 3 of ‘608 anticipates claims 4, 42 and 43. Claim 4 of ‘608 anticipates “single-chain antibody” in claim 5 and cysteine or unnatural amino acid in claim 15. Claim 11 anticipates claims 17 and 18. Claim 13 of ‘608 anticipates claims 20, 21, 23, and 24. Claim 32 anticipates claim 43. Claim 37 anticipates instant claim 50 and claim 38 anticipates instant claim 51. Claim 43 anticipates instant claims 2 and 3. Claim 44 of ‘608 anticipates instant claim 59.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant argues that the claims of the ‘608 application are patentably distinct. Applicant states that the instant application is “directed to” a compound of formula Ib with the specific branched linker, B, the representative compound being the conjugate JY201 which exhibits effective cytotoxicity against tumor cells and show superior ability of penetration into tumor tissues that traditional antibody-drug conjugates. This has been considered but not found persuasive. The claims of the ‘608 application anticipate the instant claims.
Claims 53-60 are provisionally rejected and claims 1-5, 10, 13, 15-18, 20, 21, 23, 24, 42, 43, 44, 46, 50, and 51 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4-5, 21, 24, 60-64 of copending Application No. 18/836,485(reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘485 application anticipate the instant claims. Claim 1 anticipates instant claims 1 and 44. Claim 2 anticipates claim 2 and claim 53. Claim 4 anticipates claim 4. Claim 5 anticipates claims 5, 10, 15, and 16 as well as claim 13 because SEQ ID NO:2 of ‘485 is identical to the instant SEQ ID NO:1:
Alignment result
GenCore version 6.5.2
Copyright (c) 1993 - 2025 Biocceleration Ltd.
OM protein - protein search, using sw model
Title: US-18-836-485-2
Perfect score: 2701
Sequence: 1 DIQMTQSPSSLSASVGDRVT..........PTFGQGTKVEIKRTHHHHHH 506
Scoring table: BLOSUM62
Gapop 10.0 , Gapext 0.5
Searched: 1 seqs, 506 residues
Total number of hits satisfying chosen parameters: 1
Minimum DB seq length: 0
Maximum DB seq length: inf
Post-processing: Minimum Match 0%
Maximum Match 100%
Listing first 1 summaries
Database : US-17-995-541-1.pep:*
SUMMARIES
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 2701 100.0 506 1 US-17-995-541-1 ANTIBODY-DRUG CONJ
ALIGNMENTS
RESULT 1
US-17-995-541-1
Query Match 100.0%; Score 2701; DB 1; Length 506;
Best Local Similarity 100.0%;
Matches 506; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCKASQDVSIGVAWYQQKPGKAPKLLIYSASYRYTGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSLSASVGDRVTITCKASQDVSIGVAWYQQKPGKAPKLLIYSASYRYTGVPS 60
Qy 61 RFSGSGSGTDFTLTISSLQPEDFATYYCQQYYIYPYTFGQGTKVEIKRTGGSGGSGGSGG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDFTLTISSLQPEDFATYYCQQYYIYPYTFGQGTKVEIKRTGGSGGSGGSGG 120
Qy 121 SGGEVQLVESGGGLVQPGGSLRLSCAASGFTFTDYTMDWVRQAPGKGLEWVADVNPNSGG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SGGEVQLVESGGGLVQPGGSLRLSCAASGFTFTDYTMDWVRQAPGKGLEWVADVNPNSGG 180
Qy 181 SIYNQRFKGRFTLSVDRSKNTLYLQMNSLRAEDTAVYYCARNLGPSFYFDYWGQGTLVTV 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 SIYNQRFKGRFTLSVDRSKNTLYLQMNSLRAEDTAVYYCARNLGPSFYFDYWGQGTLVTV 240
Qy 241 SSGCGSGGSGGSGGSGGEVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGK 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 SSGCGSGGSGGSGGSGGEVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGK 300
Qy 301 GLEWVARIYPTNGYTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 GLEWVARIYPTNGYTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDG 360
Qy 361 FYAMDYWGQGTLVTVSSGGSGGSGGSGGSGGDIQMTQSPSSLSASVGDRVTITCRASQDV 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 FYAMDYWGQGTLVTVSSGGSGGSGGSGGSGGDIQMTQSPSSLSASVGDRVTITCRASQDV 420
Qy 421 NTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQ 480
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Db 421 NTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQ 480
Qy 481 QHYTTPPTFGQGTKVEIKRTHHHHHH 506
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Db 481 QHYTTPPTFGQGTKVEIKRTHHHHHH 506
Claim 5 of ‘485 also anticipates instant claims 54-56. Claim 50 anticipates instant claims 57-60. Claim 21 anticipates claims 17 and 18. Claim 24 anticipates claims 20, 21, 23 and 24. Claim 60 anticipates claim 50 and claim 61 anticipates claim 51. Claim 63 anticipates claims 42, 43 and 45. The first structure of claim 63 on page 20 of the ‘485 claims anticipates the first structure listed on instant claim 46. The first structure on page 21 of the ‘485 claims anticipates the second structure listed of instant claim 46.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant argues that the ‘485 application “pursues” a compound linking a cytotoxic hydroxyl-bearing small molecule or peptide D, wherein the in vitro cytotoxicity of the compounds are demonstrated in the examples. This has been considered but not found persuasive. The claims of the ‘485 application anticipate the instant claims.
Allowable Subject Matter
Claim 61 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
All other rejections and/or objections as set forth in the prior Office action are withdrawn.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAREN A CANELLA whose telephone number is (571)272-0828. The examiner can normally be reached M-F 10-6:30.
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KAREN A. CANELLA
Examiner
Art Unit 1643
/Karen A. Canella/Primary Examiner, Art Unit 1643
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