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 .
Status of the Claims
Claims 44-84 are pending. Acknowledgment is made of the amendment to claims 44, 47, 48, and 75 in the reply filed 03/20/2026.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/20/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawn Objections/Rejections
Applicant’s amendment to the claims, filed 03/20/2026, overcomes the objection to claims 44 and 75 for minor informalities. The objection to claims 44 and 75 has been withdrawn.
Applicant’s amendment to the claims, filed 03/20/2026, overcomes the rejection of claims 44, 45, 47, 48, 50-70, 72, 74, and 76-84 under 35 U.S.C. 101 for being inoperative. The rejection of claims 44, 45, 47, 48, 50-70, 72, 74, and 76-84 has been withdrawn.
Maintained Rejections
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.
Claims 77-81 and 84 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the inhibition of Mcl-1 and the treatment of myeloma comprising administering a compound of formula (I), does not reasonably provide enablement for treating any condition requiring an anti-apoptotic inhibitor, including any cancer or autoimmune disease. 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.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is undue. These factors include, but are not limited to: (a) breadth of the claims; (b) nature of the invention; (c) state of the prior art; (d) level of one of ordinary skill in the art; (e) level of predictability in the art; (f) amount of direction provided by the inventor or joint inventor; (g) existence of working examples; and (h) quantity of experimentation needed to make or use the invention based on the content of the disclosure. {See Ex parte Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986); and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988)}.
The above factors, regarding the present invention, are summarized as follows:
Breadth of the claims
The breadth of the claim includes a method of treating a disease requiring an anti-apoptotic inhibitor, including any cancer, autoimmune disease, or immune system disease, in a patient, comprising administering a compound of the formula (I).
Nature of the invention
The nature of the invention is performance of a method of treating a disease requiring an anti-apoptotic inhibitor, including any cancer, autoimmune disease, or immune system disease in a patient, comprising administering a compound of formula (I).
State of the prior art
No single drug has been discovered that is effective in treating any and every cancer, immune disease, or autoimmune disease, including but not limited to myeloma, multiple myeloma, lymphoma, especially Non-Hodgkin Lymphoma (NHL) and Diffuse Large B-cell Lymphoma (DLBCL), and leukemia, especially Chronic Lymphocytic Leukemia (CLL), T-cell Acute Lymphoblastic Leukemia (T-ALL), B-5 cell Acute Lymphoblastic Leukemia (B-ALL) and Acute Myelogenous Leukemia (AML), bladder, brain, breast, uterus, esophagus and liver cancers, colorectal cancer, renal cancer, melanoma, ovarian cancer, prostate cancer, pancreatic cancer and lung cancer, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) (page 78 of the specification). See In re Hokum, 226 USPQ 353 (ComrPats 1985). Since the compounds are novel, there is no prior art teaching that these compounds or compounds of a similar structure are capable of treating all the diseases listed in the instant claims.
Level of one of ordinary skill in the art
The artisans performing the inventor’s or joint inventor’s method of treating a disease requiring an anti-apoptotic inhibitor, including any cancer, autoimmune disease, or immune system disease in a patient, comprising administering a compound of formula (I), would be a collaborative team of synthetic chemists and/or health practitioners, possessing commensurate degree level and/or skill in the art, as well as several years of professional experience.
Level of predictability in the art
Synthetic organic chemistry is quite unpredictable. See In re Marzocchi and Horton 169 USPQ at 367 ¶3. Similarly, it is well established that “[T]he scope of enablement varies inversely with the degree of unpredictability of the factors involved, and physiological activity is generally considered to be an unpredictable factor”. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
Amount of direction provided by the inventor
The invention lacks direction with respect to making and/or using (performing) a method of treating a disease requiring an anti-apoptotic inhibitor, including any cancer, autoimmune disease, or immune system disease in a patient, comprising administering a compound of formula (I).
Existence of working examples
The disclosure is insufficient to allow extrapolation of the limited examples to enable performing the instantly recited method of treating a disease requiring an anti-apoptotic inhibitor, including any cancer, autoimmune disease, or immune system disease in a patient, comprising administering a compound of formula (I).
Similarly, according to the specification on page 78, compounds of formula (I) are capable of treating a variety of cancers and autoimmune diseases in a patient, including, but not limited to, myeloma, multiple myeloma, lymphoma, especially Non-Hodgkin Lymphoma (NHL) and Diffuse Large B-cell Lymphoma (DLBCL), and leukemia, especially Chronic Lymphocytic Leukemia (CLL), T-cell Acute Lymphoblastic Leukemia (T-ALL), B-5 cell Acute Lymphoblastic Leukemia (B-ALL) and Acute Myelogenous Leukemia (AML), bladder, brain, breast, uterus, esophagus and liver cancers, colorectal cancer, renal cancer, melanoma, ovarian cancer, prostate cancer, pancreatic cancer and lung cancer, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).
However, the specification fails to set forth any convincing in vitro and/or in vivo assays corroborating the alleged activity in association with any of the aforementioned diseases. The specification only provides examples for the inhibition of Mcl-1 and the inhibition of tumor growth in myeloma xenografts comprising administering compounds of formula (I). There is insufficient disclosure to reasonably conclude that the method of treating a disease requiring an anti-apoptotic inhibitor, including any cancer, autoimmune disease, or immune system disease in a patient, comprising administering a compound of formula (I), as recited, would contribute to treatment of any the aforementioned diseases. The inventor or joint inventor has neither provided convincing data for any patient population, nor indicated any art recognized correlation between the disclosed data and the breadth of the claim.
Quantity of experimentation needed
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the invention was filed, would not have taught one skilled in the art how to make and/or use (perform) the full scope of the claimed invention without undue experimentation. See In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
One skilled in the art, such as a medical doctor, would be required to perform thousands of clinical trials and in vivo or in vitro assays in order to determine which compounds of formula (I) would be capable of treating which cancers, immune diseases, and autoimmune diseases. Even in vitro and in vivo assays do not always correlate to efficacy in humans and are not generally predictive of clinical efficacy.
The determination that undue experimentation would have been needed to make and use the claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached by weighing all the above noted factual considerations. See In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404. These factual considerations are discussed comprehensively in MPEP § 2164.08 (scope or breadth of the claims), § 2164.05(a) (nature of the invention and state of the prior art), § 2164.05(b) (level of one of ordinary skill), § 2164.03 (level of predictability in the art and amount of direction provided by the inventor or joint inventor), § 2164.02 (the existence of working examples) and § 2164.06 (quantity of experimentation needed to make or use the invention based on the content of the disclosure).
Based on a preponderance of the evidence presented herein, the conclusion that the inventor or joint inventor is insufficiently enabled for a method of treating a disease requiring an anti-apoptotic inhibitor, including any cancer, autoimmune disease, or immune system disease in a patient, comprising administering a compound of formula (I), is clearly justified.
Applicant Argues:
Applicant cited references that show that the Mcl-1 gene is highly expressed across certain cancer cell lines, and that certain types of cancers can lead to increased Mcl-1 expression. It was also shown that Mcl-1 is essential for sustained growth of certain tumors. Applicant cited that Mcl-1 plays a role in the survival and differentiation of some hematopoietic cell lines, some of which play a role in the development of autoimmune diseases.
Examiner Responds:
Applicant's arguments, filed 03/20/2026, have been fully considered but they are not persuasive. The expression of Mcl-1, which only occurs in some occasions after a patient has a specific type of tumor, as cited by Applicant, would not lead one to believe that inhibiting Mcl-1 would be able to treat every type of cancer, and the prior art does not indicate this. There are more factors involved than just Mcl-1 expression in the development and treatment of cancer and autoimmune diseases, and one of ordinary skill in the art would not expect that inhibiting only the Mcl-1 gene would be effective in treating any and every cancer and immune disease, even if Mcl-1 expression is involved in the type of tumor or immune disease being treated. Additionally, there is no proof that Mcl-1 is involved in every type of cancer or immune disease.
New Rejections
Over previously unpublished co-pending application
Nonstatutory 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.
Claims 44-70 and 76-81 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 91 and 172-179 of copending Application No. 18/881,336 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Application ‘336 teaches a more limited genus of compounds than the instant claims. The reference compounds have the structure Formula (I), shown below.
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221
252
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The compounds of reference claim 172 read directly on instant claims 44-70. For example, (1r,3'R,4S,7'S)-4-(3-chloroanilino)-3'-[(dimethylamino)methyl]-7’-[(2R)-2 methyl-3-{[(5R)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy)propyl]-2’,3',7,8’-tetrahydrospiro-[cyclohexane-1,6'-indeno[5,6-b][1,4]dioxine]-4-carboxylicacid, shown below, where X is NH, R1 is chlorophenyl, R16 is OH, Y1 is C(R4)(R5), R5 is H, R4 is
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100
180
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, Y2 is C(R8)(R9), R8- is H, R9- is H, Y4 is CH, Y3 is CH, R11 and R12 are taken together to form
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77
126
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, R18 is methyl substituted by NR’R”, and R’ and R” are both methyl.
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258
557
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The pharmaceutical composition and methods of treatment of reference claims 173-179 read directly on instant claims 76-81.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Advisory Notice
Claims 71-75, 82, and 83 appear allowable if rewritten in independent form.
Conclusion
Claims 44-70, 76-81, and 84 are rejected.
Claims 71-75, 82, and 83 are objected to.
THIS ACTION IS MADE FINAL. 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 RILLA M SAMSELL whose telephone number is (703)756-5841. The examiner can normally be reached Monday-Friday, 7-3.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Murray can be reached at (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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/R.M.S./Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624
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