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 .
Priority
This application is a DIV of 16/759,175 filed on 04/24/2020 now Patent number 11998584. 16/759,175 is a 371 of PCT/CN2017/120454 filed on 12/31/2017.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements submitted on 08/08/2025 and 10/09/2025 have been considered by the examiner.
Claim Status
Claims 1-17 are pending. Claim 1 is amended. Claims 9-17 are new. Claims 1-17 are being examined on the merits in this office action.
Claim Rejections - Withdrawn
The rejection of claims 1-8 under 35 U.S.C. 103 as being unpatentable over Zhao et al. (WO2014009774A1 – hereinafter “Zhao”) in view of the claim amendments and arguments.
Claim Rejections - 35 USC § 112 – Maintained
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 the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 1-17 are rejected 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. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP § 2137 states that "the written description requirement for a genus must be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
For written description, the analysis (a) considers actual reduction to practice, (b) disclosure of drawings or structural chemical formulas, (c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties, functional characteristics when coupled with known or disclosed and (d) representative number of examples.
Actual reduction to practice and (b) disclosure of drawings or structural chemical formulas:
The instant claims recite a side chain-linkage compound of Formula (IV), which can readily react to a cell-binding molecule T to form a conjugate:
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wherein
“
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” represents a single bond;
L1 and L2 are, the same or different, independently selected from O, NH, N, S, N(R3), N(R3)N(R3′), CH, CO, C(O)NH, C(O)O, polyethyleneoxy unit of formula (OCH2CH2)pOR3, or (OCH2CH—(CH3))pOR3, or NH(CH2CH2O)pR3, or NH(CH2CH(CH3)O)pR3, or N[(CH2CH2O)pR3], [(CH2CH2O)pR3′], or (OCH2CH2)pCOOR3, or CH2CH2(OCH2CH2)pCOOR3, wherein p and p′ are independently an integer selected from 0 to about 1000, or a combination of two or more thereof; C1-C8 alkyl; C2-C8 heteroalkyl, alkylcarbonyl, or heteroaryl; or (Aa)r, r=1-12 (1 to 12 amino acid units), which is composed from natural or unnatural amino acids, or the same or different sequences of dipeptide, tripeptide, tetrapeptide, pentapeptide, hexapeptide, heptapeptide, octapeptide, nonapeptide, decapeptide, undecapeptide or dodecapeptide unit;
W is a stretcher unit having C1-C18, and is a peptidic unit, a disulfide, an ester, or an amide bond; w is 1 or 2 or 3;
V1 and V2 are independently a spacer unit and selected from NH, C1-C8 alkyl, alkylcarbonyl, or (Aa)r, r=1-12 (1 to 12 amino acid units), which is composed from a natural or unnatural amino acid, or the same or different sequences of dipeptide, tripeptide, tetrapeptide, pentapeptide, hexapeptide, heptapeptide, octapeptide, nonapeptide, decapeptide, undecapeptide or dodecapeptide unit; or (CH2CH2O)p, p is 0-1000; and v1 and v2 are independently 0, 1 or 2, but v1 and v2 are not 0 at the same time; when v1 or v2 is 0, one of the side chain Q1 or Q2 fragment is absent;
Q1 and Q2 are independently represented by Formula (I-q1):
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wherein
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is a site linked to L1 or L2; G1 and G2 are independently OC(O), NHC(O), C(O), CH2, NH, OC(O)NH, NHC(O)NH, O, Ar, ArCH2, ArO, ArNH, ArS, ArNR1, or (Aa)q1; G3 is OH, SH, OR1, SR1, OC(O)R1, NHC(O)R1, C(O)R1, CH3, NH2, NR1, +NH(R1), +N(R1)(R2), C(O)OH, C(O)NH2, NHC(O)NH2, S(O)2(OH), (CH2)q1C(O)OH, (CH2)q1P(O)(OH)2, C(O)(CH2)q1C(O)OH, OC(O)(CH2)q1C(O)OH, NHC(O)(CH2)q1C(O)OH, CO(CH2)q1P(O)(OH)2, NHC(O)O(CH2)q1C(O)OH, OC(O)NH(CH2)q1C(O)OH, NHCO(CH2)q1P(O)(OH)2, NHC(O)(NH)(CH2)q1C(O)OH, Ar, ArR1, ArOH, ArNH2, ArSH, ArNHR1, or (Aa)q1; (Aa)q1 is a peptide containing the same or different sequence of natural or unnatural amino acids; X1 and X2 are independently O, CH2, S, S(O), NHNH, NH, N(R1), +NH(R1), +N(R1)(R2), C(O), OC(O), OC(O)O, OC(O)NH, or NHC(O)NH;
Y2 is O, NH, NR1, CH2, S, NHNH, or Ar; p1, p2 and p3 are independently 0-100 but are not 0 at the same time; q1 and q2 are independently 0-24;
R1, R2, R3 and R3′ are independently H, C1-C8 alkyl; C2-C8 heteroalkyl, or heterocyclic; C3-C8 aryl, Ar-alkyl, cycloalkyl, alkylcycloalkyl, heterocycloalkyl, heteroalkylcycloalkyl, carbocyclic, or alkylcarbonyl;
alternatively, any one or more of W, Q1, Q2, L1, L2, V1, or V2 can be independently absent but Q1 and Q2 are not absent at the same time;
D is tubulysin analog having following formula (II):
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or a pharmaceutically acceptable salt, hydrate, or hydrated salt; or a polymorphic crystalline structure; or an optical isomer, racemate, diastereomer or enantiomer thereof,
wherein ----- is a linkage site that links to W independently;
wherein R1, R2, R3, and R4 are independently H, C1-C8 alkyl; C2-C8 heteroalkyl, or heterocyclic; C3-C8 aryl, Ar-alkyl, cycloalkyl, alkylcycloalkyl, heterocycloalkyl, heteroalkylcycloalkyl, carbocyclic, or alkylcarbonyl; or R1 and R2, R1 and R3, R2 and R3, R3 and R4, R5 and R6, R11 and R12, or R13 and R14 form a 3-7 membered carbocyclic, cycloalkyl, heterocyclic, heterocycloalkyl, aromatic or heteroaromatic ring system; R1 and R2 can be independently absent when they link to W independently or simultaneously, Y1 is N or CH;
wherein R5, R6, R8, R10 and R11 are independently H, or C1-C4 alkyl or heteroalkyl;
wherein R7 is independently H, R14, —R14C(═O)X1R15; or —R14X1R15; X1 is O, S, S—S, NH, CH2 or NR14;
wherein R9 is selected from H, OH, —O—, ═O, —OR14, —OC(═O)R14, —OC(═O)NHR14—, —OC(═O)R14SSR15—, OP(═O)(OR14)—, —OC(═O)NR14R15, OP(═O)(OR14), or OR140P(═O)(OR15);
wherein R11 is independently H, R14, —R14C(═O)R16, —R14X2R16, —R14C(═O)X2, wherein X2 is —O—, —S—, —NH—, —N(R14)—, —O—R14—, —S—R14—, —S(═O)—R14—, or —NHR14;
wherein R12 is R15, —OH, —SH, —NH2, NH, NHNH2, —NH(R15), —OR15, —R15COR16,
R15COOR16, —R15C(O)NH2, —R15C(O)NHR17, —SR16, R15S(═O)R16, —R15P(═O)(OR17)2, —R15OP(═O)(OR17)2, —CH2OP(═O)(OR17)2, —R15SO2R17, —R15X2R16, —R15C(═O)X2, where X2 is —O—OH, SH, —S—, NH2, —NH—, —N(R15)—, —O—R15—, —S—R15—, —S(═O)—R15—, CH2 or —NHR5—;
R13 and R14 are independently H, O, S, NH, N(R15), NHNH, —OH, —SH, —NH2, NH, NHNH2, —NH(R15), —OR15, CO, —COX2, —COX2R16, R17, F, Cl, Br, I, SR16, NR16R17, N═NR16, N═R16, NO2, SOR16R17, SO2R16, SO3R16, PR16, PR16R17, POR16R17, PO2R16R17, OP(O)(OR17)2, OCH2OP(O)(OR17)2, OC(O)R17, OC(O)OP(O)(OR17)2, PO(OR16)(OR17), OP(O)(OR17)OP(O)(OR17)2, OC(O)NHR17, —O—(C4-C12 glycoside), —N—(C4-C12 glycoside); C1-C8 alkyl or heteroalkyl; C2-C8 alkenyl, alkynyl, heteroalkyl, or heterocycloalkyl; C3-C8 aryl, Ar-alkyl, carbocyclic, cycloalkyl, heteroalkylcycloalkyl, alkylcarbonyl, or heteroaryl, or C2-C8 ester, ether, or amide; or peptide containing 1-8 amino acids (NH(Aa)1-8 or CO(Aa)i-s (N-terminal or C-terminal 1-8 same or different amino acids), or polyethyleneoxy unit of formula (OCH2CH2)p or (OCH2CH(CH3))p, wherein p is an integer from 0 to about 1000, or a combination of two or more thereof; X2 is O, S, S—S, NH, CH2, OH, SH, NH2, CHR14 or NR14;
R15, R16 and R17 are independently H, C1-C8 alkyl or heteroalkyl; C2-C8 alkenyl, alkynyl, heteroalkyl, or heterocycloalkyl; C3-C8 aryl, Ar-alkyl, carbocyclic, cycloalkyl, heteroalkylcycloalkyl, alkylcarbonyl, heteroaryl, or alkylcarbonyl, or Na+, K+, Cs+, Li+, Ca2+, Mg+, Zn2+, N+(R1)(R2)(R3)(R4), or HN+(C2H5OH)3 salt;
Y1 and Y2 are independently N or CH; q is 0 or 1; when q=0, Y3 does not exist, Y4, Y5, Y6 and Y7 are independently CH, N, NH, O, S, or N(R′), thus Y2, Y4, YS, Y6 and Y7form a heteroaromatic ring of furan, pyrrole thiophene, thiazole, oxazole, imidazole, pyrazole, triazole, tetrazole, or thiadiazole; when q=1, Y3, Y4, Y5, Y6 and Y7 are independently CH or N, thus Y2, Y3, Y4, Y5, Y6 and Y7 form an aromatic ring of benzene, pyridine, pyridazine, pyrimidine, pyrazine, triazine, tetrazine, or pentazine;
LV1 is a reacting group that can be reacted with a thiol, amine, carboxylic acid, selenol, phenol or hydroxyl group on a cell-binding molecule; LV1 is selected from OH; F; Cl; Br; I; nitrophenol; N-hydroxysuccinimide (NHS); phenol; dinitrophenol; pentafluorophenol; tetrafluorophenol; difluorophenol; mono-fluorophenol; pentachlorophenol; triflate; imidazole; dichlorophenol; tetrachlorophenol; 1-hydroxybenzotriazole; tosylate; mesylate; 2-ethyl-5-phenylisoxazolium-3′-sulfonate, anhydride formed by an acid itself, or formed with another anhydride; or an intermediate molecule generated with a condensation reagent for peptide coupling reactions, or for Mitsunobu reactions; the condensation reagent is selected from: EDC (N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide), DCC (dicyclohexyl-carbodiimide), N,N′-diisopropylcarbodiimide (DIC), N-cyclohexyl-N′-(2-morpholino-ethyl)carbodiimide metho-p-toluenesulfonate (CMC, or CME-CDI), 1,1′-carbonyldiimi-dazole (CDI), TBTU (0-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate), N,N,N′,N′-tetramethyl-O-(1H-benzo-triazol-1-yl)-uronium hexafluoro-phosphate (HBTU), (benzotriazol-1-yloxy)tris(dimethylamino)-phosphonium hexafluorophosphate (BOP), (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (PyBOP), diethyl cyanophosphonate (DEPC), chloro-N,N,N′,N′-tetra-methylformamidiniumhexafluorophosphate, 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU), 1-[(dimethylamino)-(morpholino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridine-1-ium 3-oxide hexafluoro-phosphate (HDMA), 2-chloro-1,3-dimethyl-imidazolidinium hexafluorophosphate (CIP), chlorotripyrrolidinophosphonium hexafluorophosphate (PyCloP), fluoro-N,N,N′,N′-bis(tetramethylene)-formamidinium hexafluorophosphate (BTFFH), N,N,N′,N′-tetramethyl-S-(1-oxido-2-pyridyl)thiuronium hexafluorophosphate, O-(2-oxo-1(2H)pyridyl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TPTU), S-(1-oxido-2-pyridyl)-N,N,N′,N′-tetramethylthiuronium tetrafluoroborate, O-[(ethoxycarbonyl)-cyanomethylenamino]-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HOTU), (1-cyano-2-ethoxy-2-oxoethylidenaminooxy) dimethylamino-morpholino-carbenium hexafluorophosphate (COMU), O-(benzotriazol-1-yl)-N,N,N′,N′-bis(tetramethylene)-uronium hexafluorophosphate (HBPyU), N-benzyl-N′-cyclohexyl-carbodiimide (with, or without polymer-bound), dipyrrolidino(N-succinimidyl-oxy)carbenium hexafluoro-phosphate (HSPyU), chlorodipyrrolidinocarbenium hexafluorophosphate (PyClU), 2-chloro-1,3-dimethylimidazoli-dinium tetrafluoroborate(CIB), (benzotriazol-1-yloxy)dipiperidino-carbenium hexafluorophosphate (HBPipU), 0-(6-chlorobenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TCTU), bromotris(dimethylamino)-phosphonium hexafluorophosphate (BroP), propylphosphonic anhydride (PPACA, T3P©), 2-morpholinoethyl isocyanide (MEI), N,N,N′,N′-tetramethyl-O—(N-succinimidyl)uronium hexafluorophosphate (HSTU), 2-bromo-1-ethyl-pyridinium tetrafluoroborate (BEP), O-[(ethoxycarbonyl)cyano-methylenamino]-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TOTU), 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholiniumchloride (MMTM, DMTMM), N,N,N′,N′-tetramethyl-O—(N-succinimidyl)uronium tetrafluoroborate (TSTU), O-(3,4-dihydro-4-oxo-1,2,3-benzotriazin-3-yl)-N,N,N′,N′-tetramethyluronium tetrafluoro-borate (TDBTU),1,1′-(azodicarbonyl)-dipiperidine (ADD), di-(4-chlorobenzyl)azodicarboxylate (DCAD), di-tert-butyl azodicarboxylate (DBAD), diisopropyl azodicarboxylate (DIAD), diethyl azodicarboxylate (DEAD)
Applicant has reduced to practice the compounds recited in claim 8 and the compounds are limited to D (tubulysin) being
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The compounds reduced to practice have different linkers. Examiner notes that the instant claims currently recite the compound of Formula IV with a laundry list of possible groups or variables and the claims are not a representation of any particular species. Written description issues may also arise if the knowledge and level of skill in the art would not have permitted the ordinary artisan to immediately envisage the claimed product arising from the disclosed process. See, e.g., Fujikawa v. Wattanasin, 93 F.3d 1559, 1571, 39 USPQ2d 1895, 1905 (Fed. Cir. 1996) (a "laundry list" disclosure of every possible moiety does not necessarily constitute a written description of every species in a genus because it would not "reasonably lead" those skilled in the art to any particular species); In re Ruschig, 379 F.2d 990, 995, 154 USPQ 118, 123 (CCPA 1967) (See MPEP 2162.1 (A).
sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties
A correlation between structure and function, for the instantly claimed genus of compounds, is not disclosed in the specification. Examiner notes that the species disclosed in the instant application comprise a similar tubulysin structure linked to a monoclonal antibody or reacting group using different types of linkers. The instant claims however, list numerous variables or functional groups that could be attached to the compound leading to the numerous types of linkers and thus numerous compounds. Thus, the instant claims are not limited to a particular structure given the variability of the linkers that could be generated.
Representative number of examples
A “representative number of species” means the species which are adequately described are a representative of the entire genus. Therefore, when there is a substantial variation within a genus, the applicant must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) ("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). See MPEP 2163.3 (ii).
The elected species and the compounds recited in the application specification are not a representation of the entire genus recited in the claims. The instant Examples are focused on producing the compounds that all have the same tubulysin structure, linker and a monoclonal antibody or reacting group. The Examples do not disclose the numerous linkers that could be generated from all the variables recited in the instant Formula IV. Further, the Examples do not disclose the numerous linkers linked to the numerous reacting groups recited in the instant claims. Thus, the specification fails to provide adequate written description for the genus of compounds claimed and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Response to Arguments
Applicant's arguments filed 09/30/2025 have been fully considered but they are not persuasive.
Applicant argues that the claims were amended to redefine W, Q1, Q2, , L1, L2, V1, V2, LV1.
Examiner notes that the amendments do not overcome the written description rejection. Applicant has reduced to practice the compounds recited in claim 8 and the compounds are limited to D (tubulysin) being
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The compounds reduced to practice have different linkers. Examiner notes that the instant claims currently recite the compound of Formula IV with a laundry list of possible groups or variables and the claims are not a representation of any particular species. Written description issues may also arise if the knowledge and level of skill in the art would not have permitted the ordinary artisan to immediately envisage the claimed product arising from the disclosed process. See, e.g., Fujikawa v. Wattanasin, 93 F.3d 1559, 1571, 39 USPQ2d 1895, 1905 (Fed. Cir. 1996) (a "laundry list" disclosure of every possible moiety does not necessarily constitute a written description of every species in a genus because it would not "reasonably lead" those skilled in the art to any particular species); In re Ruschig, 379 F.2d 990, 995, 154 USPQ 118, 123 (CCPA 1967) (See MPEP 2162.1 (A). The instant Examples are focused on producing the compounds that all have the same tubulysin structure, linker and a monoclonal antibody or reacting group. The Examples do not disclose the numerous linkers that could be generated from all the variables recited in the instant Formula IV. Further, the Examples do not disclose the numerous linkers linked to the numerous reacting groups recited in the instant claims. Thus, the specification fails to provide adequate written description for the genus of compounds claimed and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Double Patenting - Maintained
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 1-2, 5-6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. US10399941B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the patent recite a side chain-linkaged conjugate compound of the Formula (I):
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(claim 1), wherein the conjugate has the structure
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(claims 2-3), and the structure
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(claim 5).
The instant claims recite a side chain-linkage compound of Formula (IV), which can readily react to a cell-binding molecule T to form a conjugate:
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Q1 and Q2 are independently represented by Formula (I-q1):
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D is tubulysin analog having following formula (II):
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or a pharmaceutically acceptable salt, hydrate, or hydrated salt; or a polymorphic crystalline structure; or an optical isomer, racemate, diastereomer or enantiomer.
The claims of the patent anticipate the instant claims.
Regarding claims 2 and 5, the claims of the patent recite wherein the conjugate comprises
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(claim 5) which comprises maleimide and comprises the instant tubulysin.
Regarding claim 6, the claims of the patent recite wherein the conjugate comprises
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(claim 13), which comprises the instant 3rd structure.
Claims 1-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 27-35 of copending Application No. 18/706,734. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the copending application recite a compound drug linker complex that comprises the formula
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or
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wherein LV1 and LV2 is
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and linkers such as
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(claim 27) that is attached to a monoclonal antibody (claim 28-31) and wherein the drugs are PEG (claim 32), wherein the tubulysin analog
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specifically,
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(claim 33).
The instant claims recite a side chain-linkage compound of Formula (IV), which can readily react to a cell-binding molecule T to form a conjugate:
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Q1 and Q2 are independently represented by Formula (I-q1):
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D is tubulysin analog having following formula (II):
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or a pharmaceutically acceptable salt, hydrate, or hydrated salt; or a polymorphic crystalline structure; or an optical isomer, racemate, diastereomer or enantiomer.
The claims of the copending application anticipate the instant claims.
Regarding claims 2-7, claims of the copending application recite a compound drug linker complex that comprises the formula
PNG
media_image11.png
51
241
media_image11.png
Greyscale
or
PNG
media_image12.png
99
264
media_image12.png
Greyscale
wherein LV1 and LV2 is
PNG
media_image13.png
155
496
media_image13.png
Greyscale
and linkers such as
PNG
media_image14.png
206
1005
media_image14.png
Greyscale
(claim 27) that is attached to a monoclonal antibody (claim 28-31) and wherein the drugs are PEG (claim 32), wherein the tubulysin analog
PNG
media_image15.png
216
788
media_image15.png
Greyscale
specifically,
PNG
media_image16.png
142
655
media_image16.png
Greyscale
(claim 33).
Regarding claim 8, the claims of the copending application teaches compounds such as
PNG
media_image17.png
247
1057
media_image17.png
Greyscale
(claim 35).
Regarding claim 9, the claims of the copending application recite that the variables can be C1-C8 alkyl, or the structures below
PNG
media_image18.png
565
787
media_image18.png
Greyscale
(claim 27).
Regarding claims 12-17, the claims of the copending application recite
PNG
media_image19.png
201
796
media_image19.png
Greyscale
PNG
media_image20.png
265
1107
media_image20.png
Greyscale
PNG
media_image21.png
471
973
media_image21.png
Greyscale
Claims 1-8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 41-44, 46-52 of copending Application No. 18/706,736. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the copending application recite an antibody drug conjugate comprising the tubulysin analog
PNG
media_image22.png
150
548
media_image22.png
Greyscale
PNG
media_image23.png
312
827
media_image23.png
Greyscale
(claims 41-42).
That the conjugate comprises the linker such as
PNG
media_image24.png
145
816
media_image24.png
Greyscale
and
PNG
media_image25.png
221
781
media_image25.png
Greyscale
(claim 43-44, 46-52).
The instant claims recite a side chain-linkage compound of Formula (IV), which can readily react to a cell-binding molecule T to form a conjugate:
PNG
media_image1.png
207
738
media_image1.png
Greyscale
Q1 and Q2 are independently represented by Formula (I-q1):
PNG
media_image3.png
282
893
media_image3.png
Greyscale
D is tubulysin analog having following formula (II):
PNG
media_image5.png
443
1300
media_image5.png
Greyscale
or a pharmaceutically acceptable salt, hydrate, or hydrated salt; or a polymorphic crystalline structure; or an optical isomer, racemate, diastereomer or enantiomer.
The claims of the copending application anticipate the instant claims.
Regarding claims 2-8, claims of the copending application recite a compound drug linker complex that comprises the formula
PNG
media_image11.png
51
241
media_image11.png
Greyscale
or
PNG
media_image12.png
99
264
media_image12.png
Greyscale
wherein LV1 and LV2 is
PNG
media_image13.png
155
496
media_image13.png
Greyscale
and linkers such as
PNG
media_image14.png
206
1005
media_image14.png
Greyscale
(claims 43-44), wherein the tubulysin analog
PNG
media_image22.png
150
548
media_image22.png
Greyscale
(claim 41-42).
Claims 1-8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 24-28, 31-34 of copending Application No. 18/706,741. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the copending application recite a drug-linker complex of the formula
PNG
media_image26.png
77
427
media_image26.png
Greyscale
wherein LV1 and LV2 include
PNG
media_image27.png
112
188
media_image27.png
Greyscale
wherein the linker includes
PNG
media_image28.png
150
842
media_image28.png
Greyscale
or
PNG
media_image29.png
92
641
media_image29.png
Greyscale
(claim 24-28), wherein the tubulysin analog includes
PNG
media_image30.png
131
625
media_image30.png
Greyscale
(claim 31-34).
The instant claims recite a side chain-linkage compound of Formula (IV), which can readily react to a cell-binding molecule T to form a conjugate:
PNG
media_image1.png
207
738
media_image1.png
Greyscale
Q1 and Q2 are independently represented by Formula (I-q1):
PNG
media_image3.png
282
893
media_image3.png
Greyscale
D is tubulysin analog having following formula (II):
PNG
media_image5.png
443
1300
media_image5.png
Greyscale
or a pharmaceutically acceptable salt, hydrate, or hydrated salt; or a polymorphic crystalline structure; or an optical isomer, racemate, diastereomer or enantiomer.
The claims of the copending application anticipate the instant claims.
Regarding claims 2-8, claims of the copending application recite a compound drug linker complex that comprises the formula
PNG
media_image11.png
51
241
media_image11.png
Greyscale
or
PNG
media_image12.png
99
264
media_image12.png
Greyscale
wherein LV1 and LV2 is
PNG
media_image13.png
155
496
media_image13.png
Greyscale
and linkers such as
PNG
media_image14.png
206
1005
media_image14.png
Greyscale
(claims 24-28), wherein the tubulysin analog
PNG
media_image22.png
150
548
media_image22.png
Greyscale
(claim 31-34).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's argument has been fully considered but is not found persuasive because only compliance with objections or requirements as to form not necessary for further consideration of the claims may be held in abeyance until allowable subject matter is indicated. MPEP §804. Therefore, the nonstatutory double patenting rejections are maintained.
Conclusion
No claims are allowed.
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 Mercy H. Sabila whose telephone number is (571)272-2562. The examiner can normally be reached Monday - Friday 5:00 am - 3:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G. Garyu can be reached at (571)270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MERCY H SABILA/Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654