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 .
DETAILED ACTION
Response to Amendment
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 1/23/2026 has been entered.
Newly amended Claims 27-34 and 42-52 are pending in the application and examined herein.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied and constitute the complete set presently being applied to the instant application.
Response to Arguments
Applicant argues regarding the rejections issued over Andersson that no Andersson compound is within the scope of the amended Formula II and does not suggest modification. Also, Andersson merely performs a virtual screening of the taught compounds. Applicant’s argument is fully considered but not persuasive. First, the newly amended Formula II genus now only encompasses homologs of Andersson Compound 17. Although, Andersson does not explicitly teach the modification of Compound 17 to form a homolog encompassed within the amended Formula II, it is known that substituting a methyl group for a hydrogen is an obvious modification and expected to yield a compound with similar properties (In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977); MPEP 2144.09). Secondly, a successful virtual screening of the Andersson compounds suggests in vitro and in vivo activity. Such models are used to predict activity of the compounds in particular environments and forecast their binding properties before clinical use. Because no evidence is supplied to suggest the contrary, it stands that a virtual screening is a valid method of determining compounds capable of binding specific targets. The rejections over Andersson are reissued below and amended to reflect the above teachings regarding homologous structures.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 33 and 49 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Regarding Claim 33, the scope of the claim encompasses all p53 mutant tumors because a tumor is either with or without MSI. Both variants are claimed. Claim 33 therefore does not further limit the scope of Claim 27.
Claim 49 describes a compound (Left) which is not a theophylline derivative like those compounds encompassed by Formula II (Right):
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Therefore, Claim 49 improperly broadens the scope of Claim 27.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claims 27-34, 42-48, and 50 are rejected under 35 U.S.C. 103 as being unpatentable over Andersson (Journal of Medicinal Chemistry. 2012, 55, 7706-7718) in view of Bachmann (Molecular Cancer 2014, 13:125, 1-24) and Ramqvist (Oncogene (1993), 8, 1495-1500).
Andersson teaches ADP-ribosyltransferases or ARTDs are useful in DNA repair and remodeling and inhibitors of ARTDs, specifically ARTD1/2, are known for the treatment of cancers. Andersson teaches Compound 17 as a potential ARTD8 binder (Page 7710, Table 1; Page 7711, Figure 5):
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in which the following definitions of examined Formula II apply: R1, R2, R3, R4, R6, and R7 are H; R5 is Me, an unsubstituted alkyl; X is sulfur; and n is 2. The Andersson compound differs from the examined genus of Formula II in that R5 is methyl rather than a group recited in the examined definition of Formula II. Andersson does not teach modifying said compound. However, compounds which are homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See MPEP 2144.09. Therefore, one seeking to form an ARTD8 binding compound would find it obvious to modify Compound 17 of Andersson to form a homolog as described in the MPEP because the difference between H and CH3 is a single methylene, CH2. The resulting homolog is encompassed within Formula II:
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Andersson teaches the specific role and function of ARTD8 is not known (Abstract) and fails to disclose the use of additional therapies in the treatment of ARTD8-mediated cancers.
Bachmann teaches “ARTD8 has been shown to mediate survival in c-Myc-driven Burkitt lymphoma [BL]-like tumors in vivo and multiple myeloma [MM]” (Page 2, Right Col, Para 2). Bachmann confirms ARTD8 can play a role in specific cancers similar to ARTD1/2 inhibitors as taught in Andersson.
Regarding Claim 33, the scope of the claim encompasses all tumors because a tumor is either with or without MSI. Both variants are claimed.
Regarding Claim 34, Bachmann further teaches “overexpression of DTX3L, ARTD8 and ARTD9 is indeed associated with enhanced STAT1 (pSTAT1-S727)-signaling” (Page 3, Left Col, Para 3). With respect to increased STAT1 signaling, “the combined targeted inhibition of STAT1, ARTD8, ARTD9 and/or DTX3L could increase the efficacy of chemotherapy or radiation treatment in prostate and other high-risk tumor types with an increased STAT1 signaling” (Abstract).
Bachmann fails to teach the presence of p53 mutations in Burkitt lymphomas (BL).
Ramqvist teaches that most, at least 60%, of BL cell lines carry a mutated p53 cell line (Abstract).
Therefore, one of ordinary skill in the art would find it obvious to treat the most common form of BL, having a p53 mutation as required by Claim 33, with Compound 17 of Andersson which modulates the activity of ARTD8 and thereby BL. The same artisan, motivated by Bachmann’s teaching of the use of chemo- and radiation therapy in BL, would administer Compound 17 to modulate ARTD8 activity as well as use chemo- and/or radiation therapy to supplement the treatment, expecting “increased efficacy” in the treatment of BL before the effective filing date of the instant application.
Claims 27-33, 42-48, and 50-52 are rejected under 35 U.S.C. 103 as being unpatentable over Andersson (Journal of Medicinal Chemistry. 2012, 55, 7706-7718) in view of Zhao (Int J Clin Exp Pathol 2016;9(2):1829-1838) and Li (World J Gastroenterol 2015 January 7; 21(1): 84-93).
Andersson teaches ADP-ribosyltransferases or ARTDs are useful in DNA repair and remodeling and inhibitors of ARTDs, specifically ARTD1/2, are known for the treatment of cancers. Andersson teaches Compound 17 as a potential ARTD8 binder (Page 7710, Table 1; Page 7711, Figure 5):
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in which the following definitions of examined Formula II apply: R1, R2, R3, R4, R6, and R7 are H; R5 is Me, an unsubstituted alkyl; X is sulfur; and n is 2. The Andersson compound differs from the examined genus of Formula II in that R5 is methyl rather than a group recited in the examined definition of Formula II. Andersson does not teach modifying said compound. However, compounds which are homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See MPEP 2144.09. Therefore, one seeking to form an ARTD8 binding compound would find it obvious to modify Compound 17 of Andersson to form a homolog as described in the MPEP because the difference between H and CH3 is a single methylene, CH2. The resulting homolog is encompassed within Formula II:
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Andersson teaches the specific role and function of ARTD8 is not known (Abstract).
Zhao teaches ARTD8 is elevated in colorectal cancers (Page 1831-1832):
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“It suggested that ARTD8 probably participate in the progression of colorectal carcinoma” (Page 1833, Para 2). Further, “The expression of ARTD8 has been seen in various tumor tissues including B-cell lymphomas, hepatocellular carcinoma, and multiple myeloma. As a member of the B aggressive lymphoma (BAL) family, ARTD8 is expressed in lymphoid organs and lymphocyte cell lines and it is linked to the aggressiveness of B-cell lymphomas in diffuse large B-cell lymphomas” (Page 1833, Para 2).
Regarding Claim 33, the scope of the claim encompasses all tumors because a tumor is either with or without MSI. Both variants are claimed.
Zhao does not teach a relationship between ARTD8 and CRC.
Li teaches “[i]t is generally known that the progression of CRC follows mutations of the APC, K-Ras, and p53 genes. p53 is the most commonly mutated gene in human cancers” and “p53 mutation in CRC occurs in 34% of the proximal colon tumors, and in 45% of the distal colorectal tumors” (Page 87, P53 MUTATION…).
Therefore, one of skill in the art seeking to treat common forms of CRC with mutant p53 variants, including progressed variants wherein p53 and KRAS are mutated, would find it obvious to use an ARTD8 inhibitor like Compound 17 taught in Andersson to treat said disease because Zhao suggests ARTD8 inhibitors are effective for the treatment of cancers with elevated ARTD8 like CRC. The same artisan before the effective filing date of the instant claims would have reasonably expected the effective treatment of the mutated cancer using the Andersson compound because mutant-p53 CRC commonly expresses increased ARTD8 as a characteristic of its pathology.
Conclusion
No claim is allowable.
Claim 49 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Richard G. Peckham whose telephone number is (703)756-4621. The examiner can normally be reached 7:30am - 4:30pm.
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/RICHARD GRANT PECKHAM/Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627