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 1-3, 56, 60-62, 65, 68, 69, 74-82 and 84 are pending in this application.
Claim Rejections - 35 USC § 112
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 76-78, 81, 82 and 84 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
In evaluating the enablement question, several factors are to be considered. In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988); Ex parte Forman, 230 USPQ 546. The factors include: 1) The nature of the invention, 2) the state of the prior art, 3) the predictability or lack thereof in the art, 4) the amount of direction or guidance present, 5) the presence or absence of working examples, 6) the breadth of the claims, and 7) the quantity of experimentation needed.
The nature of the instant invention has claims, which embrace substituted sulfonyl benzamide compound.
HOW TO USE: Claims 76-78, 81, 82 and 84 is drawn to a method of modulating the level of activity of BCL-2 or BCL-2/BCL-XL and the method of treating one or more disease or disorder, which is associated with BCL-2 or BCL-2/BCL-XL protein activity. Any evidence presented must be commensurate in scope with the claims and must clearly demonstrate the effectiveness of the claimed compounds. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. The scope of claims 76-78, 81, 82 and 84 includes diseases and/or conditions not even known at this time, which may be associated with BCL-2 or BCL-2/BCL-XL protein activity. While the treatment of chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL) and acute myeloid leukemia (AML) has been linked with p38α mitogen-activated protein kinases in the art does not recognize use of such inhibitors as broad-based drugs for treating all disorders instantly embraced. “Ccancer” cannot be deemed enabled. The notion that a compound could be effective against cancer in general is contrary to our current understanding of how pharmacological work. All attempts to find a pharmaceutical to treat cancer, etc. generally have thus failed.
In view of the lack of direction provided in the specification regarding starting materials, the lack of working examples, and the general unpredictability of chemical reaction, it would take an undue amount of experimentation for one skilled in the art to make the claimed compounds and therefore practice the invention. To be enabling, the specification of a patent must teach those skilled in the art how to make and use the scope of the claimed invention without undue experimentation. The applicants are not entitled to preempt the efforts of others. The test for determining compliance with 35 U.S.C. § 112, is whether the applicants have clearly defined their invention.
The claims also include the treatment of cancer. Evidence involving a single compound and two types of cancer was not found sufficient to establish the enablement of claims directed to a method of treating seven types of cancer with members of a class of several compounds in re Buting 163 USPQ 689. The remarkable advances in chemotherapy have seen the development of specific compounds to treat specific types of cancer. The great diversity of diseases falling within the “tumor” category means that it is contrary to medical understanding that any agent (let alone a genus of thousands of compounds) could be generally effective against such diseases. The intractability of these disorders is clear evidence that the skill level in this art is low relative to the difficulty of the task.
Where the utility is unusual or difficult to treat or speculative, the examiner has authority to require evidence that tests relied upon are reasonably predictive of in vivo efficacy by those skilled in the art. See In re Ruskin, 148 USPQ 221; Ex parte Jovanovics, 211 USPQ 907; MPEP 2164.05(a).
Patent Protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable. Tossing out the mere germ of an idea does not constitute enabling disclosure. Genentech Inc. v. Novo Nordisk 42 USPQ2d 1001.
As stated in the MPEP, 2164.08 ''[t]he Federal Circuit has repeatedly held that the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. ln re Wright, 999 F.2d 1557, 1561 27 USPQ2d 1510, 1513 (Fed. Cir. 1993). Nevertheless, not everything necessary to practice the invention need be disclosed. In fact, what is well known is best omitted. In re Buchner, 929 F.2d 660, 661, 18 USPQ2d 1331, 1332 (Fed. Cir. 1991). AII that is necessary is that one skilled in the art be able to practice the claimed invention, given the level of knowledge and skill in the art. Further the scope of enablement must only bear a reasonable correlation to the scope of the claims. See, e.g., In re Fisher, 427 F.2d 833, 839,166 USPQ 18, 24 (CCPA 1970). As concerns the breadth of a claim relevant to enablement, the only relevant concern should be whether the scope of enablement provided to one skilled in the art by the disclosure is commensurate with the scope of protection sought by the claims. In re Moore, 439 F.2d 1232, 1236, 169 USPQ 236, 239 (CCPA 1971). See also Plant Genetic Sys., N.V. v. DeKalb Genetics Corp., 315 F.3d 1335, 1339, 65 USPQ2d 1452, 1455 (Fed. Cir. 2003) (alleged pioneer status of invention irrelevant to enablement determination.''
Claims 81, 82 and 84 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (preAlA), first paragraph, because the specification, while being enabling for doxorubicin, irinotecan, topotecan, etoposide, mitomycin, bendamustine, chlorambucil, cyclophosphamide, ifosfamide, carmustine, melphalan and bleomycin does not reasonably provide enablement for anti-tumor agent generally. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The nature of the instant invention has claims which embrace substituted sulfonyl benzamide compounds.
The method of the instant invention where the compounds of Formula I is co- administered with an additional active ingredient that is an anti-tumor agent. The specification does not define that which is intended in the use of a chemotherapeutic agent, an anti-tumor agent, a radiation therapy agent, an immunotherapy agent, an anti-angiogenesis agent, a targeted therapy agent, a cellular therapy agent, a gene therapy agent, a hormonal therapy agent, an antiviral agent, an antibiotic, an analgesic, an antioxidant, a metal chelator, a cytokine, a BTK inhibitor, a BCR-ABL inhibitor, a JAK3 inhibitor, or a PARP inhibitor. The following is a list of chemotherapeutic agents such as busulfan, mesna, daunorubicin, pefloxacin mesylate, 5-fluorouridine, pefloxacin, etc., an anti-tumor agents such as oleanonic acid, tasisulam, danthron, erianin, CHD1Li 6.11, ursonic acid, quinocetone, betulinicaldehyde, YL-109, deferasirox, EF24, monomethylauristatin F hydrochloride, etc., radiation therapy agents such as gemcitabine, doxorubicin, T0070907, vadimezan, LY2090314, rosiglitazone maleate, pertuzumab, pamrevlumab, tafasitamab, NDRG1 antibody, leronlimab, demcizumab, polatuzumab, ascrinvacumab, anti-PMEL, Anti-siglec-15, labetuzumab, Anti-CHI3L1, Anti-Lewis Y, erlizumab, Anti-PDGFRB, Anti-S100A4, CPI-455 HCl, artesunate, BML-277, boceprevir, atazanavir, isotretinoin, CGP 57380, MYCi361, amodiaquine, etc., immunotherapy agents such as XYL-1, etc., anti-angiogenesis agents such as ATN-161, vitamin E, withaferin A, ranibizumab, vulinacimab, vanucizumab, tunicamycin, eflornithine hydrochloride hydrate, hydroxychloroquine, E7820, pentostatin, danshensu, etc., targeted therapy agents such as dasatinib, sunitinib, dasatinib monohydrate, calderasib, etoposide phosphate, ribociclib succinate hydrate, amifostine, temoporfin, BBI-355, etc., cellular therapy agents such as vemurafenib, aloxistatin, vadimezan, erdafitinib, calpeptin, isotretinoin, tapinarof, spermine, pentostatin, radretumab, cordycepin, etc., gene therapy agents such as quizartinib, metformin hydrochloride, GANT61, ataluren, streptozotocin, pitavastatin calcium, progesterone, plixorafenib, grisnilimab, rinucumab, pelabresib, unesbulin, olmutinib, taletrectinib, etc., hormonal therapy agents such as talarozole, calderasib, etoposide phosphate, amifostine, temoporfin, sulfobromophthalein disodium salt, piboserod, medicarpin, veliparib dihydrochloride, ferric citrate, anthrone, culmerciclib, tradipitant, bismuth subnitrate, Trilaciclib dihydrochloride, etc., antiviral agents such as boceprevir, prunus serrulate extract, etc., antibiotics such as puromycin dihydrochloride, brefeldin A, doxycycline, idarubicin HCl, minocycline HCl, blasticidin S hydrochloride, azithromycin, puromycin, daptomycin, linezolid, tunicamycin, rifabutin, kanamycin sulfate, roxithromycin, tetracycline, tobramycin, thiamphenicol, nadifloxacin, enrofloxacin, spiramycin, gamithromycin, etc., analgesics such as etosalamide, naphazoline, etc., antioxidants such as gallic acid, proanthocyanidins, oolong tea extract, Morchella extract, bee pollen extract, moringa oleifera leaf extract, Basella rubra extract, pine bark extract, 2,2-diphenyl-1-picrylhydrazyl, etc., metal chelators such as llomastat, doxycycline, batimastat, dolutegravir, marimastat, tetrathiomolybdate, hematoxylin, TPEN, auraptene, abametapir, pyrithione, metalaxyl, tioxolone, gluconolactone, succimer, pentetic acid, tropolone, isocytosine, solasodine, triolein, emeramide, etc., cytokines such as , aprepitant, resiquimod, apilimod, tranilast, cepharanthine, diacerein, oclacitinib maleate, muscone, benznidazole, EC330, CPYPP, GSK5182, enokizumab, guselkumab, itolizumab, butoconazole nitrate, atibuclimab, clazakizumab, bakkenolide A, tyrosol, zansecimab, certolizumab, Lenzilumab, perflubron, golimumab, demethyleneberberine, etc., BTK inhibitors such as ibrutinib, acalabrutinib, spebrutinib, tirabrutinib hydrochloride, olmutinib, evobrutinib, fenebrutinib, branebrutinib, avitinib, Zanubrutinib, pirtobrutinib, nemtabrutinib, orelabrutinib, remibrutinib, tolebrutinib, etc., BCR-ABL inhibitors such as dasatinib, imatinib, ponatinib, nilotinib, bosutinib, tozasertib, nocodazole, degrasyn, danusertib, bafetinib, rebastinib, asciminib, berbamine, olverembatinib, radotinib, vodobatinib, flumatinib, etc., JAK3 inhibitors such as ruxolitinib, ibrutinib, dorsomorphin, tofacitinib, ruxolitinib, fedratinib, baricitinib, momelotinib, filgotinib, gandotinib, cerdulatinib, decernotinib, abrocitinib, solcitinib, ritlecitinib, Zanubrutinib, brepocitinib, ivarmacitinib, oclacitinib, delgocitinib, ilginatinib, etc., PARP inhibitors such as Olaparib, talazoparib, veliparib, rucaparib phosphate, niraparib, rucaparib, iniparib, berberine chloride, pamiparib, stenoparib, 3-aminobenzamide, saruparib, benzamide, fluzoparib, picolinamide, atamparib, venadaparib, nesuparib, nudifloramide, etc., which includes chemotherapeutic agents, anti-tumor agents, radiation therapy agents, immunotherapy agents, anti-angiogenesis agents, targeted therapy agents, cellular therapy agents, gene therapy agents, hormonal therapy agents, antiviral agents, antibiotics, analgesics, antioxidants, metal chelators, cytokines, BTK inhibitors, BCR-ABL inhibitors, JAK3 inhibitors, PARP inhibitors which are neither supported nor contemplated. This is just a few chemotherapeutic agents, an anti-tumor agents, radiation therapy agents, immunotherapy agents, anti-angiogenesis agents, targeted therapy agents, cellular therapy agents, gene therapy agents, hormonal therapy agents, antiviral agents, antibiotics, analgesics, antioxidants, metal chelators, cytokines, BTK inhibitors, BCR-ABL inhibitors, JAK3 inhibitors, PARP inhibitors embraced by “chemotherapeutic agents, an anti-tumor agents, radiation therapy agents, immunotherapy agents, anti-angiogenesis agents, targeted therapy agents, cellular therapy agents, gene therapy agents, hormonal therapy agents, antiviral agents, antibiotics, analgesics, antioxidants, metal chelators, cytokines, BTK inhibitors, BCR-ABL inhibitors, JAK3 inhibitors, PARP inhibitors”.
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 1-3, 56, 60-62, 65, 68, 69, 74-82 and 84 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. The following reasons apply:
Claims 1, 3, and claims dependent thereon are vague and indefinite in that it is not known what is meant by the definition of R3 where R3 is absent where R3 is the substituent bound to L1.
Claim 1 and claims dependent thereon are vague and indefinite in that it is not known what is meant by the definition of L2 where L2 contains the moieties C1-6 alkenyl, C1-6 alkynyl, hetero- C1-6 alkenyl and hetero- C1-6 alkynyl. C1-6 alkenyl and C1-6 alkynyl can never have a C1.
Claims 1, 3, and claims dependent thereon are vague and indefinite in that it is not known what is meant by the definition of Rc which includes the moieties -Ra2-NHRa3 and -Ra2-NHC(O)Ra3 where Ra2 is a divalent in each of these moieties but the definition of Ra2 is monovalent.
Claim 61 and claims dependent thereon are vague and indefinite in that it is not known what is meant by the definition of -L1-R3 where -L1-R3 is absent.
Claim 65 recites the limitation "
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" in the definition of Ra. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 2, 61 and 75-80 is/are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Guo et al., WO 2019/210828 (U.S. equivalents 2024/0376104, 12,077,536; and 11,420,968). Guo teaches the compounds, compositions and method of use of the compounds of Formula I where W is CH, n is 2, R1 is -NO2 and -NH-L3-Ra wherein L3 is CH2 and Ra is tetrahydro-2H-pyran-4-yl; R2 is hydrogen; L1 is O; R3 is pyrrolo[2,3-b]pyridine-5-yl; L2 is phenyl or cyclohexen-1-yl; R4 is isoindolin-2-yl or cyclopenta[c]pyrrol-2(1H)-yl; and Rf is phenyl or butyl as set forth in examples A87, C182 and C193 each of which is claimed in U.S. ‘968. The generic structure of Guo encompasses the instantly claimed compounds, compositions and method of use of the compounds of Formula I (see Formula (I), column 3) as claimed herein. Examples A87, C182 and C193 each anticipate the compounds of Formula I where W is CH, n is 2, R1 is -NO2 and -NH-L3-Ra wherein L3 is CH2 and Ra is tetrahydro-2H-pyran-4-yl; R2 is hydrogen; L1 is O; R3 is pyrrolo[2,3-b]pyridine-5-yl; L2 which corresponds to Ring A is a cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heterocyclyl, or heteroaryl, each of which is optionally substituted with 1 to 4 substituents R2; R2, at each occurrence, is independently selected from the group consisting of hydrogen, halogen, -C1-8alkyl, -C2-8alkenyl, C2-8alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, oxo, -CN, -NO2, -OR2a, -SO2R2a, -COR2a, -CO2R2a, -CONR2aR2b, -C(═NR2a)NR2bR2c, -NR2aR2b, -NR2aCOR2b, -NR2aCONR2bR2c, -NR2aCO2R2b, -NR2aSONR2bR2c, -NR2aSO2NR2bR2c, or -NR2aSO2R2b, each of said -C1-8alkyl, -C2-8alkenyl, -C2-8alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with halogen, hydroxy, -C1-8alkyoxy, cycloalkyl, heterocyclyl, aryl, or heteroaryl; R2a, R2b, and R2c, are each independently hydrogen, -C1-8alkyl, -C2-8alkenyl, -C2-8alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of said -C1-8alkyl, -C2-8alkenyl, -C2-8alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with halogen, hydroxy or -C1-8alkyoxy; R4 which corresponds to Ring B cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heterocyclyl, or heteroaryl, each of which is optionally substituted with 1 to 4 substituents R1; R1, at each occurrence, is independently selected from the group consisting of hydrogen, halogen, -C1-8alkyl, -C2-8alkenyl, -C2-8alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, oxo, -CN, -NO2, -OR1a, -SO2R1a, -COR1a, -CO2R1a, -CONR1aR1b, -C(═NR1a)NR1bR1c, -NR1aR1b, -NR1aCOR1b, -NR1aCONR1bR1c, -NR1aCO2R1b, -NR1aSONR1bR1c, -NR1aSO2NR1bR1c, or -NR1aSO2R1b, wherein said -C1-8alkyl, -C2-8alkenyl, -C2-8alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl are each independently optionally substituted with 1 to 4 substituents R1d. The compounds of the instant invention are generically embraced by Guo in view of the interchange ability of R1, R2, R3, R4, R5, L1, L2, L3, L4, m, Ring A and Ring B substituents of the sulfonylbenzamide ring system. Thus, one of ordinary skill in the art at the time the invention was made would have been motivated to select for example
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for the Ring B of the reference as well as other possibilities from the generically disclosed alternatives of the reference and in so doing obtain the instant compounds in view of the equivalency teachings outlined above.
Claim(s) 1-3, 56, 60-62, 65, 68, 69, 74-82 and 84 is/are rejected under 35 U.S.C. 102(1)(a) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Zhang et al. WO 2021/223736 (U.S. equivalent 2023/0159527). Zhang teaches the compounds, compositions and method of use of the compounds of Formula I where W is N, n is 2, R1 is -NO2 and -NH-L3-Ra wherein L3 is CH2 and Ra is tetrahydro-2H-pyran-4-yl or cyclohexyl wherein Rc is hydroxy and CH3; R2 is hydrogen; L1 is O; R3 is pyrrolo[2,3-b]pyridine-5-yl; L2 is
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; R4 is
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; and Rg is phenyl substituted by isopropyl or R4 is
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wherein Rg is phenyl substituted by Br as set forth in examples on pages 875, 896 and 897. The generic structure of Zhang encompasses the instantly claimed compounds, compositions and method of use of the compounds of Formula I (see Formula (I), column 3) as claimed herein. Examples on pages 875, 896 and 897 each anticipate the compounds of Formula I where W is N, n is 2, R1 is -NO2 and -NH-L3-Ra wherein L3 is CH2 and Ra is tetrahydro-2H-pyran-4-yl or cyclohexyl wherein Rc is hydroxy and CH3; R2 is hydrogen; L1 is O; R3 is pyrrolo[2,3-b]pyridine-5-yl; L2 which corresponds to Ring A is a spirocyclic ring system
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; R4 which corresponds to Ring B is
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where two R4 substituents together with the atoms to which they are attached form a C3-10 cycloalkyl or heterocyclic ring of 4 to 12 members containing 1, 2 or 3 heteroatoms independently selected from oxygen, sulfur, nitrogen and phosphorus. The compounds of the instant invention are generically embraced by Zhang in view of the interchange ability of X1, X2, X3, Y1, Y2, Y3, Z, B, A, W, R1, R2, R3, R4, R5, R6, R7, L1, L2, L3, L4, q, n, n1, n2, p, p1, p2, m, m1 and m2 substituents of the sulfonylbenzamide ring system. Thus, one of ordinary skill in the art at the time the invention was made would have been motivated to select for example
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for the
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of the reference as well as other possibilities from the generically disclosed alternatives of the reference and in so doing obtain the instant compounds in view of the equivalency teachings outlined above.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRENDA L COLEMAN whose telephone number is (571)272-0665. The examiner can normally be reached Mon-Fri 10-6 (flex).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey H. Murray can be reached on 571-272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRENDA L COLEMAN/Primary Examiner, Art Unit 1624