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 .
Election/Restrictions
Applicant’s election without traverse of
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in the reply filed on 12/15/2025 is acknowledged.
The elected species reads on claims 1, 6, 8, 11, 13, 17, 19, 21, 23, 25, 47, 48, and 262.
Claims 26, 28, 29, and 256-261 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/15/2025.
Current Status of 18/037,697
The amended claims of 11/16/2023 were used to write this Office Action.
Claims 1, 6, 8, 11, 13, 17, 19, 21, 23, 25, 47, 48, and 262 are examined on the merits.
Priority
This application is a national stage entry of PCT/US21/59668, which claims priority to US provisional application 63/115,317.
The instant claims find support from the provisional application. Therefore, the instant application’s effective filing date is 11/18/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 6/23/2023, 09/12/2023, 11/16/2023, 12/14/2023, 09/05/2024, 09/06/2024, 02/13/2025, 06/18/2025, 07/11/2025, 08/12/2025, 09/15/2025, and 12/15/2025, are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1, 11, 13, 17, 19, 21, 23, 25, 47, 48, and 262 are rejected under 35 U.S.C. 103 as being unpatentable over Curis (WO 2019089580, previously cited in the IDS of 06/23/2023) in view of Espinosa (Espinosa et al. “Activation of the NF-kappaB signaling pathway in diffuse large B-cell lymphoma: clinical implications”, Histopathology, October 2008).
Curis teaches the elected species (CAS# 1801344-12-6 compound fourth compound on page 92). This teaches the compound from claims 1, 17, 19, 21, 23, 25, 47, and 48.
Curis teaches a method of treating of cancer using the elected species (ref. claim 35). Specifically, Curis uses the elected species (also called CA-4948) to treat a mice model of Diffuse large B-cell lymphoma (DLBCL) (example 2 on page 69-70). This teaches the disease of claim 262.
Curis does not teach obtaining a biological sample or measuring an expression level of a phosphorylated NF-KB.
Espinosa characterized the activation of the nuclear factor (NF)-kappaB pathway in diffuse large B-cell lymphoma (DLBCL) by immunohistochemistry (abstract).
Espinosa teaches obtaining a biological sample (“cells” Abstract) of claim 1.
Espinosa teaches DLBCL were evaluated with antibodies against phosphorylated p65 (p-p65); p-p65 positive tumors showed a better response to chemotherapy (P = 0.025) and a trend to increased event-free survival (P = 0.08). This helps teach claim 11. This also helps comparing the level of expression of the phosphorylated NF-KB to a reference level of expression of phosphorylated NF-KB of claim 1.
Espinosa teaches measuring an expression level of a phosphorylated NF-KB (p-p65) in a biological sample (cells) (abstract) of claim 1.
Espinosa teaches that the expression of NF-KB p-p65 is nuclear expression (abstract). This helps teach claim 13.
An artisan would have been motivated to look for biomarkers before administering a treatment because elevated p-p65 showed a better response to chemotherapy (Espinosa abstract). The artisan would expect to be able to measure the expression level of a phosphorylated NF-KB, such as p-p65, in DBLCL cells (Espinosa abstract). The artisan would also be motivated and expected to administer a treatment of the elected species (Curis example 2 on page 69-70 ) for a disease with an increased expression level of a phosphorylated NF-KB, such as p-p65 (Espinosa abstract). This teaches claims 1, 11, 13, 17, 19, 21, 23, 25, 47, 48, and 262.
Claim(s) 1, 6, 7, 17, 19, 21, 23, 25, 47, 48, and 262 are rejected under 35 U.S.C. 103 as being unpatentable over Curis (WO 2019089580) in view of Schmitt (Schmitt et al,. “p50 (NF-κB1) is an effector protein in the cytotoxic response to DNA methylation damage”, Mol Cell, December 2011).
Curis teaches the elected species (CAS# 1801344-12-6 compound fourth compound on page 92). This teaches the compound from claims 1, 17, 19, 21, 23, 25, 47, and 48.
Curis teaches a method of treating of cancer using the elected species (ref. claim 35). This teaches the disease of claim 262.
Curis does not teach obtaining a biological sample or measuring an expression level of a phosphorylated NF-KB.
Schmitt teaches that phosphorylation of p50 results in the inhibition of NF-κB DNA binding; Expression of an un-phosphorylateable p50 mutant blocks inhibition of NF-κB regulated anti-apoptotic gene expression and attenuates SN1-methylator-induced cytotoxicity (summary). This helps teaches that when p50 is phosphorylated, it shuts downs anti-apoptotic genes (pro-survival). Schmitt teaches p-p50 was from a nuclear extract (page 3). This helps teach claims 6 and 8.
An artisan would have been motivated to look for biomarkers before administering a treatment because elevated p-p50 shuts downs anti-apoptotic genes, which is pro-survival (Schmitt summary). The artisan would expect to be able to measure the expression level of a phosphorylated NF-KB, such as p-p50, in cancer cells (“nuclear extract” Schmitt page 3). The artisan would also be motivated and expected to administer a treatment of the elected species (Curis example 2 on page 69-70 ) for cancer (Curis ref. claim 35). This teaches claims 1, 6, 8, 17, 19, 21, 23, 25, 47, 48, and 262.
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 1, 11, 13, 17, 19, 21, 23, 25, 47, 48, and 262 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claim 1 of U.S. Patent No. US10758518 (CURIS) in view of Espinosa (Espinosa et al,. “Activation of the NF-kappaB signaling pathway in diffuse large B-cell lymphoma: clinical implications”, Histopathology, October 2008).
Curis teaches the elected species (ref claim 1). This teaches the compound from claims 1, 17, 19, 21, 23, 25, 47, and 48.
Curis teaches a method of treating of cancer (DLBCL) using the elected species (ref. claim 1). This teaches the disease of claim 262.
Curis does not teach obtaining a biological sample or measuring an expression level of a phosphorylated NF-KB.
Espinosa characterized the activation of the nuclear factor (NF)-kappaB pathway in diffuse large B-cell lymphoma (DLBCL) by immunohistochemistry (abstract).
Espinosa teaches obtaining a biological sample (“cells” Abstract) of claim 1.
Espinosa teaches DLBCL were evaluated with antibodies against phosphorylated p65 (p-p65); p-p65 positive tumors showed a better response to chemotherapy (P = 0.025) and a trend to increased event-free survival (P = 0.08). This helps teach claim 11. This also helps comparing the level of expression of the phosphorylated NF-KB to a reference level of expression of phosphorylated NF-KB of claim 1.
Espinosa teaches measuring an expression level of a phosphorylated NF-KB (p-p65) in a biological sample (cells) (abstract) of claim 1.
Espinosa teaches that the expression of NF-KB p-p65 is nuclear expression (abstract). This helps teach claim 13.
An artisan would have been motivated to look for biomarkers before administering a treatment because elevated p-p65 showed a better response to chemotherapy (Espinosa abstract). The artisan would expect to be able to measure the expression level of a phosphorylated NF-KB, such as p-p65, in DBLCL cells (Espinosa abstract). The artisan would also be motivated and expected to administer a treatment of the elected species (Curis ref claim 1) for a disease with an increased expression level of a phosphorylated NF-KB, such as p-p65 (Espinosa abstract). This teaches claims 1, 11, 13, 17, 19, 21, 23, 25, 47, 48, and 262.
Claim(s) 1, 6, 7, 17, 19, 21, 23, 25, 47, 48, and 262 rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claim 1 of U.S. Patent No. US10758518 (CURIS) in view of Schmitt (Schmitt et al,. “p50 (NF-κB1) is an effector protein in the cytotoxic response to DNA methylation damage”, Mol Cell, December 2011).
Curis teaches the elected species (ref claim 1). This teaches the compound from claims 1, 17, 19, 21, 23, 25, 47, and 48.
Curis teaches a method of treating of cancer (DLBCL) using the elected species (ref. claim 1). This teaches the disease of claim 262.
Curis does not teach obtaining a biological sample or measuring an expression level of a phosphorylated NF-KB.
Schmitt teaches that phosphorylation of p50 results in the inhibition of NF-κB DNA binding; Expression of an un-phosphorylateable p50 mutant blocks inhibition of NF-κB regulated anti-apoptotic gene expression and attenuates SN1-methylator-induced cytotoxicity (summary). This helps teaches that when p50 is phosphorylated, it shuts downs anti-apoptotic genes (pro-survival). Schmitt teaches p-p50 was from a nuclear extract (page 3). This helps teach claims 6 and 8.
An artisan would have been motivated to look for biomarkers before administering a treatment because elevated p-p50 shuts downs anti-apoptotic genes, which is pro-survival (Schmitt summary). The artisan would expect to be able to measure the expression level of a phosphorylated NF-KB, such as p-p50, in cancer cells (“nuclear extract” Schmitt page 3). The artisan would also be motivated and expected to administer a treatment of the elected species (Curis ref claim 1) for cancer (Curis ref. claim 1). This teaches claims 1, 6, 8, 17, 19, 21, 23, 25, 47, 48, and 262.
Claims 1, 11, 13, 17, 19, 21, 23, 25, 47, 48, and 262 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claim 1 of U.S. Patent No. US12178821 (CURIS) in view of Espinosa (Espinosa et al,. “Activation of the NF-kappaB signaling pathway in diffuse large B-cell lymphoma: clinical implications”, Histopathology, October 2008).
Curis teaches the elected species (ref claim 23). This teaches the compound from claims 1, 17, 19, 21, 23, 25, 47, and 48.
Curis teaches a method of treating of cancer (DLBCL) using the elected species (ref. claim 1 and ref claim 23). This teaches the disease of claim 262.
Curis does not teach obtaining a biological sample or measuring an expression level of a phosphorylated NF-KB.
Espinosa characterized the activation of the nuclear factor (NF)-kappaB pathway in diffuse large B-cell lymphoma (DLBCL) by immunohistochemistry (abstract).
Espinosa teaches obtaining a biological sample (“cells” Abstract) of claim 1.
Espinosa teaches DLBCL were evaluated with antibodies against phosphorylated p65 (p-p65); p-p65 positive tumors showed a better response to chemotherapy (P = 0.025) and a trend to increased event-free survival (P = 0.08). This helps teach claim 11. This also helps comparing the level of expression of the phosphorylated NF-KB to a reference level of expression of phosphorylated NF-KB of claim 1.
Espinosa teaches measuring an expression level of a phosphorylated NF-KB (p-p65) in a biological sample (cells) (abstract) of claim 1.
Espinosa teaches that the expression of NF-KB p-p65 is nuclear expression (abstract). This helps teach claim 13.
An artisan would have been motivated to look for biomarkers before administering a treatment because elevated p-p65 showed a better response to chemotherapy (Espinosa abstract). The artisan would expect to be able to measure the expression level of a phosphorylated NF-KB, such as p-p65, in DBLCL cells (Espinosa abstract). The artisan would also be motivated and expected to administer a treatment of the elected species (Curis ref claim 1 and 23) for a disease with an increased expression level of a phosphorylated NF-KB, such as p-p65 (Espinosa abstract). This teaches claims 1, 11, 13, 17, 19, 21, 23, 25, 47, 48, and 262.
Claim(s) 1, 6, 7, 17, 19, 21, 23, 25, 47, 48, and 262 rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claim 1 of U.S. Patent No. US12178821 (CURIS) in view of Schmitt (Schmitt et al,. “p50 (NF-κB1) is an effector protein in the cytotoxic response to DNA methylation damage”, Mol Cell, December 2011).
Curis teaches the elected species (ref claim 23). This teaches the compound from claims 1, 17, 19, 21, 23, 25, 47, and 48.
Curis teaches a method of treating of cancer (DLBCL) using the elected species (ref. claim 1). This teaches the disease of claim 262.
Curis does not teach obtaining a biological sample or measuring an expression level of a phosphorylated NF-KB.
Schmitt teaches that phosphorylation of p50 results in the inhibition of NF-κB DNA binding; Expression of an un-phosphorylateable p50 mutant blocks inhibition of NF-κB regulated anti-apoptotic gene expression and attenuates SN1-methylator-induced cytotoxicity (summary). This helps teaches that when p50 is phosphorylated, it shuts downs anti-apoptotic genes (pro-survival). Schmitt teaches p-p50 was from a nuclear extract (page 3). This helps teach claims 6 and 8.
An artisan would have been motivated to look for biomarkers before administering a treatment because elevated p-p50 shuts downs anti-apoptotic genes, which is pro-survival (Schmitt summary). The artisan would expect to be able to measure the expression level of a phosphorylated NF-KB, such as p-p50, in cancer cells (“nuclear extract” Schmitt page 3). The artisan would also be motivated and expected to administer a treatment of the elected species (Curis ref claim 23) for cancer (Curis ref. claim 1). This teaches claims 1, 6, 8, 17, 19, 21, 23, 25, 47, 48, and 262.
Claims 1, 11, 13, 17, 19, 21, 23, 25, 47, 48, and 262 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claim 1 of U.S. PG PB No. 2023310444 (CURIS) in view of Espinosa (Espinosa et al,. “Activation of the NF-kappaB signaling pathway in diffuse large B-cell lymphoma: clinical implications”, Histopathology, October 2008).
Curis teaches the elected species (ref claim 1). This teaches the compound from claims 1, 17, 19, 21, 23, 25, 47, and 48.
Curis teaches a method of treating of cancer using the elected species (ref. claim 67). This teaches the disease of claim 262.
Curis does not teach obtaining a biological sample or measuring an expression level of a phosphorylated NF-KB.
Espinosa characterized the activation of the nuclear factor (NF)-kappaB pathway in diffuse large B-cell lymphoma (DLBCL) by immunohistochemistry (abstract).
Espinosa teaches obtaining a biological sample (“cells” Abstract) of claim 1.
Espinosa teaches DLBCL were evaluated with antibodies against phosphorylated p65 (p-p65); p-p65 positive tumors showed a better response to chemotherapy (P = 0.025) and a trend to increased event-free survival (P = 0.08). This helps teach claim 11. This also helps comparing the level of expression of the phosphorylated NF-KB to a reference level of expression of phosphorylated NF-KB of claim 1.
Espinosa teaches measuring an expression level of a phosphorylated NF-KB (p-p65) in a biological sample (cells) (abstract) of claim 1.
Espinosa teaches that the expression of NF-KB p-p65 is nuclear expression (abstract). This helps teach claim 13.
An artisan would have been motivated to look for biomarkers before administering a treatment because elevated p-p65 showed a better response to chemotherapy (Espinosa abstract). The artisan would expect to be able to measure the expression level of a phosphorylated NF-KB, such as p-p65, in DBLCL cells (Espinosa abstract). The artisan would also be motivated and expected to administer a treatment of the elected species (Curis ref claim 1) for a disease with an increased expression level of a phosphorylated NF-KB, such as p-p65 (Espinosa abstract). This teaches claims 1, 11, 13, 17, 19, 21, 23, 25, 47, 48, and 262.
Claim(s) 1, 6, 7, 17, 19, 21, 23, 25, 47, 48, and 262 rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claim 1 of U.S. PG Pub 2023310444 (CURIS) in view of Schmitt (Schmitt et al,. “p50 (NF-κB1) is an effector protein in the cytotoxic response to DNA methylation damage”, Mol Cell, December 2011).
Curis teaches the elected species (ref claim 1). This teaches the compound from claims 1, 17, 19, 21, 23, 25, 47, and 48.
Curis teaches a method of treating of cancer (DLBCL) using the elected species (ref. claim 67). This teaches the disease of claim 262.
Curis does not teach obtaining a biological sample or measuring an expression level of a phosphorylated NF-KB.
Schmitt teaches that phosphorylation of p50 results in the inhibition of NF-κB DNA binding; Expression of an un-phosphorylateable p50 mutant blocks inhibition of NF-κB regulated anti-apoptotic gene expression and attenuates SN1-methylator-induced cytotoxicity (summary). This helps teaches that when p50 is phosphorylated, it shuts downs anti-apoptotic genes (pro-survival). Schmitt teaches p-p50 was from a nuclear extract (page 3). This helps teach claims 6 and 8.
An artisan would have been motivated to look for biomarkers before administering a treatment because elevated p-p50 shuts downs anti-apoptotic genes, which is pro-survival (Schmitt summary). The artisan would expect to be able to measure the expression level of a phosphorylated NF-KB, such as p-p50, in cancer cells (“nuclear extract” Schmitt page 3). The artisan would also be motivated and expected to administer a treatment of the elected species (Curis ref claim 1) for cancer (Curis ref. claim 67). This teaches claims 1, 6, 8, 17, 19, 21, 23, 25, 47, 48, and 262.
Conclusion
No claims are allowed as currently written.
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/G.A.H./ Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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