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 continuation of U.S. Application No. 17/598,389 and is a U.S. National Phase application under 35 U.S.C. § 371 of PCT Application No. PCT/ US2020/026799, filed April 06, 2020 which claims priority under 35 U.S.C. § 119(e) from U.S. Provisional Application Serial No. 62/832125, filed on April 10, 2019.
Claim Status
Claims 1-6, 9, 11-12 and 14-17 are currently active and subject to examination.
Claim Rejections – Withdrawn
The rejection of claims 1, 4 and 6-8 under 35 U.S.C. 102(a)(1) as being anticipated by “N-(1H-indazol-7-yl)-1H-pyrazole-4-sulfonamide” (PubChem CID: 60911247, Published October 19, 2012; herein referred to as “PubChem A”) (of record IDS dated 08/20/2025, NPL cite no. 1) is withdrawn.
The rejection of claims 1, 4 and 6-8 under 35 U.S.C. 102(a)(1) as being anticipated by “N-(1H-indazol-7-yl)-1-methylpyrazole-4-sulfonamide” (PubChem CID: 47309930, Published November 26, 2010; of record IDS dated 08/20/2025, herein referred to as “PubChem B”) (of record, IDS dated 08/20/2025, NPL cite no 4) is withdrawn.
The rejection of claims 1, 4 and 6-8 under 35 U.S.C. 102(a)(1) as being anticipated by “1-tert-butyl-N-(1H-indazol-7-yl)-3,5-dimethylpyrazole-4-sulfonamide” (PubChem CID: 53609448, Published December 3, 2011; herein referred to as “PubChem C”) (of record, IDS dated 08/20/2025, NPL cite no. 3) is withdrawn.
The rejection of claims 1, 4 and 6-8 under 35 U.S.C. 102(a)(1) as being anticipated by “N-(1H-indol-7-yl)-3,5-dimethyl-1H-pyrazole-4-sulfonamide” (PubChem CID: 110867609, Published January 18, 2016; herein referred to as “PubChem D”) (of record, IDS dated 08/20/2025, NPL cite no 5) is withdrawn.
The above rejections were overcome by Applicant’s amendments to the claims.
Claims 7, 8, 10 and 13 have been cancelled. The rejection of those claims is withdrawn as moot.
The rejection of claims 1-13 under 35 U.S.C. 103 as being unpatentable over Yoshino et al. (US5767283A, Published June 16, 1998), as applied to claims 1-12 above, and further in view of Gray et al. (US 11,807,606 B2, Published November 7, 2023, Priority Date January 25, 2018) (of record, IDS dated 08/20/2025, U.S. patent cite no. 4) is withdrawn.
Gray was cited in this rejection primarily for the synthesis scheme of claim 13. Claim 13 was cancelled so the above rejection is withdrawn as duplicative.
The provisional rejection of claims 1-13 on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 9-11, and 14-16 of copending Application No. 17/598,389 (reference application) is withdrawn because copending Application No. 17/598,389 was abandoned.
Claim Rejections – 35 USC § 103 – Previously Presented
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.
The rejection of claims 1-6, 9, 11-12, 14 and 16 under 35 U.S.C. 103 as being unpatentable over Yoshino et al. (US5767283A, Published June 16, 1998) (of record, IDS dated 08/20/2025, U.S. patent cite no. 3) is maintained.
The rejection of claims 1-6, 9, 11-12, 14 and 16-17 under 35 U.S.C. 103 as being unpatentable over Gray et al. (US 11,807,606 B2, Published November 7, 2023, Priority Date January 25, 2018) (of record, IDS dated 08/20/2025, U.S. patent cite no. 4) in view of Liang et al. (Bioorganic & Medicinal Chemistry Letters, Vol. 26, Issue 16, 15 August 2016, p. 4036-4041) (of record, IDS dated 08/20/2025, NPL cite no. 2) is maintained.
Claims 14, 16 and 17 are newly added but are rejected on the same grounds as previously presented.
Response to Arguments
Applicant argues that the § 103 rejections are expressly shown to be hindsight bias because at page 7 of the action, a compound falling within claim 1 and labeled “drawn by examiner” is introduced before the scope and content of the prior art is described and that “[t]he correct logic to follow in order to determine the obviousness for avoiding hindsight” requires the Graham inquiries to be performed in a particular sequence (Remarks, pp. 13-14). This argument was fully considered but is not persuasive.
Graham v. John Deere Co., Inc., 383 U.S. 1 (1966) sets out the factual inquiries underlying an obviousness determination, but it does not prescribe any order in which those findings must be presented in an Office action. The relevant inquiry for hindsight bias is whether the rejection relies on knowledge gleaned only from Applicant’s disclosure. The compound appearing at page 7 of the prior Office action was constructed from the language of claim 1 itself, not from Applicant’s specification. Identifying a compound which claim 1 reads on is a necessary predicate to the Graham inquiry (ascertaining the differences between the claimed invention and the prior art) because the differences cannot be ascertained without first determining the scope of the claimed invention. Every factual finding supporting the rejection is drawn from Yoshino, Gray or Liang, each of which is prior art of record.
Applicant’s separate complaint that compound 46 is “not one of Applicant’s exemplary compounds” (Remarks, p. 15) is not accurate. Compound 46 was addressed because it was expressly recited in then-pending claim 10. The genus of claim 1 still reads on compound 46, which is “one of Applicant’s exemplary compounds.”
Applicant argues that the Examiner “arbitrarily selects” Example 55 of Yoshino, that a lead compound analysis is required, and that the cited paragraph of Yoshino “simply lists 30 different types of heterocyclic rings” with “no indication anywhere that suggest a pyrazole is preferred or comparable to imidazole” (Remarks, pp. 14-15). These arguments were fully considered but are not persuasive.
Applicant’s own authority is dispositive of the correct lead compound framing. As Applicant correctly notes “[a] lead-compound analysis is not required where the prior-art references expressly suggest the proposed modification. SIBIA Neurosciences, Inc. v. Cadus Pharm. Corp., 225 F.3d 1349, 1359 (Fed. Cir. 2000) (“The express teachings in the art provide the motivation and suggestion to modify [the prior art]”) (Remarks, p. 13). This is precisely the situation here.
Yoshino’s general formula is
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and A is expressly defined as follows: “such aromatic ring defined with respect to A include pyrrole, pyrazole, imidazole…” (Yoshino, col. 2, ll. 27-28) (emphasis added). Pyrazole and imidazole are therefore not merely two entries on an undifferentiated list of heterocycles. Rather, they are two expressly enumerated lists of alternatives for the same structural position. Yoshino Example 55 places imidazole at that position and substituting pyrazole at that position is a substitution that Yoshino expressly proposes. This is an express statement in the prior art of recognized equivalence, not an equivalence supplied by Applicant’s disclosure or by the Examiner. See MPEP § 2144.06 (substituting equivalents known for the same purpose is prima facie obvious where the equivalence is recognized in the prior art).
Applicant’s assertion that Yoshino contains no indication that pyrazole is a “preferred” substituent misapprehends the standard. A reference is prior art for all that it teaches, including embodiments that are not recognized as preferred:
A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v.Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989). See also Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005) (reference disclosing optional inclusion of a particular component teaches compositions that both do and do not contain that component); Celeritas Technologies Ltd. v. Rockwell International Corp., 150 F.3d 1354, 1361, 47 USPQ2d 1516, 1522-23 (Fed. Cir. 1998) (The court held that the prior art anticipated the claims even though it taught away from the claimed invention. “The fact that a modem with a single carrier data signal is shown to be less than optimal does not vitiate the fact that it is disclosed.”).
MPEP § 2131.
A showing of preference is not required. The question is whether the prior art suggests the modification with a reasonable expectation of success, not whether it identified the claimed compound as an optimal choice.
Applicant argues that Yoshino’s Formula I “goes on for two full columns and represents thousands of compounds,” and that a POSITA would have faced “thousands of molecular possibilities” (Remarks, pp. 15-16. This argument was fully considered but is not persuasive. The rejection does not depend on a POSITA testing the entire genus of Yoshino. Yoshino reduced the genus to practice in a limited number of exemplified compounds, one of which, example 55, is the positional isomer of a compound falling squarely within amended claim 1, differing only by the placement of a single ring nitrogen. Where the prior art differs from the claimed compound by a single, expressly contemplated structural variation, structural similarity alone supplies the requisite reasonable expectation of success (See MPEP § 2144.09).
Applicant argues that of the 84 exemplified compounds in Yoshino, “only 3 had an IC50 value that was worse than Example 55,” and askes why a POSITA would “choose a compound with one of the worst IC50 value and not the 75+ compounds with better IC50 values” (Remarks, pp. 16-17). This argument was fully considered but is not persuasive.
First, Applicant’s premise reinforces the rejection because Applicant’s premise concedes that Yoshino’s exemplified indole-7-yl heteroarylsulfonamides are, as a class, active antitumor agents. If the entire exemplified class is active against colon cancer cells, and Example 55 (imidazole at the A position) itself outperforms the control (IC50 of 0.59 for the test compound vs. 2.0 for the control; Yoshino, Cols. 11-12, Table 1-1), a POSITA would have had a reasonable expectation that the corresponding pyrazole analog, a compound which Yoshino’s generic formula encompasses, would likewise be active. The control was not vehicle, but rather a known active compound CQS:
Pharmacological Experimental Examples will now be described to illustrate the effect of the compound of the present invention, wherein 2-sulfanylamido-5-chloroquinoxaline (CQS: Japanese Patent Laid-Open No. 62-426), which is a known heterobicyclic sulfonamide, was used as the control for the evaluation of the effect.
Yoshino, col. 10, ll. 49-54;
Further, 2-sulfanylamidoquinoxaline derivatives (US-A4931433) and N-(2-anilino-3-pyridinyl)benzenesulfonamide derivatives (EP-A472053) have been reported as aromatic sulfonamide antitumor agents.
Yoshino, col. 1, ll. 22-25.
Second, a reference that identifies more potent alternatives is not a teaching away. “Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). ‘A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use.” In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994)’” (MPEP § 2123). Applicant has not identified anything in Yoshino that criticizes, discredits, or discourages the use of the pyrazole at the A position, and could not, because Yoshino expressly names the pyrazole there.
Applicant argues that the chemical arts are “notoriously unpredictable,” that slight modification of a substituent can lead to a great difference in potency, efficacy and toxicity (Remarks, p. 17). These arguments were fully considered but are not persuasive. Obviousness requires a reasonable expectation of success, not absolute predictability (See, e.g., In re O’Farrell, 853 F.2d 894, 903, 7 USPQ2d 1673, 1681 (Fed. Cir. 1988)). Generalized assertions that the chemical arts are unpredictable, unsupported by evidence directed towards the specific modification at issue, do not rebut the prima facie case of obviousness where compounds have a very close structural relationship and a similar utility:
A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) (discussed in more detail below) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990) (discussed below and in MPEP § 2144) for an extensive review of the case law pertaining to obviousness based on close structural similarity of chemical compounds. See also MPEP § 2144.08, subsection II.A.4.(c).
MPEP § 2144.09.
Sanofi-Synthelabo is inapposite. There, the claimed compound was a single enantiomer resolved from the racemate, the contributions of the individual enantiomers to the properties of the racemate were unknown, and the patentee introduced evidence of unexpected results where all the therapeutic activity resided in one enantiomer while all the neurotoxicity resided in the other (“resolving the racemate was not mere routine experimentation and that it was unexpected that the desirable activity of clopidogrel would be found only in the d-enantiomer”). Here, the modification is not a stereochemical resolution where one enantiomer had unexpected properties. It is the substitution of one five-membered nitrogen ring for another where the reference expressly identifies both as suitable. And unlike the patentee in Sanofi-Synthelabo, Applicant has submitted no evidence of unexpected results. Should the Applicant wish to rely on unexpected properties of the claimed compounds relative to the closest prior art, the Applicant is invited to submit a declaration of that effect commensurate with the scope of the claims.
Applicant argues that Gray teaches “thousands of sulfonamide derivatives… 71 of which are exemplified, and all of which have six-membered rings attached to the sulfur atom” and that combining a “randomly selected compound in Yoshino” with “one of the 70+ compounds in Gray” would not yield the claimed pyrazole sulfonamides having RBM39 degradation activity (Remarks, p. 18). This argument was fully considered but is not persuasive. With regards to the rejection of Yoshino in view of Gray, Gray is relied upon for its teachings with respect to now cancelled claim 13, for a synthesis scheme in which the sulfonyl is bonded to chlorine (Gray, col. 35).
Applicant’s observation that the claimed compounds possess “particular RBM39 protein degradation qualities” does not distinguish the claims (Remarks, p. 21). The present claims recite compounds, compositions, and a method of treating cancer. They do not recite an RBM39 degradation limitation. Regardless, where the prior art renders the claimed compound obvious, the discovery of a previously unappreciated property or mechanism of action of that compound does not confer patentability. (See MPEP § 2112.I).
Applicant argues that nothing would motivate a POSITA to select the identified compound form Gray or to substitute a chlorophenyl moiety with a 2-cyanoethyl-pyrazole moiety or ethyl-pyrazole moiety, and that Liang in fact demonstrates unpredictability and contradicts the Office’s position that these substituents are interchangeable (Remarks, pp. 18-19). These arguments were fully considered but are not persuasive. Liang is relied upon as evidence of the art-recognized relationship between substituted aryl and substituted pyrazole groups occupying the same position on a common scaffold (bioisosterism). Liang’s Tables 3 and 4 report that relationship directed. Across Table 3, the substituted aryl and six-membered heteroaryl analogs exhibit inhibitory activities (IC50s) spanning approximately 5.3 to 35.9 nM and across Tbale 4, the substituted pyrazole analogs exhibit IC50s spanning approximately 5.6 to 15.9 nM (Liang, pp. 4038-4039). The two sets overlap substantially. In particular, the 4-chlorophenyl analog (example 37) and the methyl pyrazole analog (example 44) differ by less than two-fold, which is the comparison on which the rejection relies.
Applicant’s reliance on Liang’s compounds 41 and 43 as showing a difference in properties of factor 10 or 100 (Remarks, p. 21) is not supported by the data. In Liang’s Table 3, compound 41 exhibits an IC50 of 10 nM and compound 43 an IC50 of 5.3 nM, a difference of less than two-fold in the enzyme assay. The larger difference the Applicant identifies appears in the cell-based assay, and Liang attributes these difference to permeability and plasma protein binding, rather than to intrinsic target activity. Applicant’s own quotation from Liang makes this point: the methyl substituted pyrazole “showed slightly better potency in spite of reduced permeability, presumably due to reduced hPPB for this analog.” This statement describes the pyrazole analog performing comparably to, or better than, the aryl lead in cells, supporting rather than contradicting, the reasonable expectation that altering an aryl to pyrazole would produce a compound with similar or better properties.
Applicant’s remaining characterization of Liang, that the authors began from a flawed lead, obtained a crystal structure, and synthesized numerous analogs, establishes only that Liang’s authors conducted an optimization study. It does not establish that a POSITA would have lacked a reasonable expectation that replacing an aryl with a pyrazolyl would yield an active compound. Liang affirmatively shows this expectation. As noted in the prior Office action for the parent application, a slight difference in potency does not demonstrate dissimilarity, it demonstrates similarity.
Applicant request that the Examiner identify “the specific passage or passages, or the drawing or drawings, which contain the necessary teaching, suggestion and/or disclosure required by law,” and alternatively, that the Examiner enter an affidavit substantiating any reliance on personal expertise (Remarks, pp. 21-22).
Every factual finding underlying the rejections is supported by a citation of record. For convenience the principal passages are: Yoshino, col. 1, ll. 45-65 (general formula (I)); col. 2, ll. 22-33 (identification of pyrazole and imidazole rings as substituents for ring A); col. 2, ll. 10-20 (pharmaceutical compositions, methods of treating tumors); cols. 11-12, Table 1-1 (in vitro antitumor activity against colon cancer cells); col. 4 (synthesis of compounds of formula (I)); col. 23 (Example 7); col. 24 (Example 8); col. 28 (Example 18); col. 29 (Example 21); col. 31 (Example 26); col. 33 (Example 30); col. 36 (Example 37); col. 38 (Example 55); col. 44 (Example 60). Gray, col. 1 (targeted degradation of RBM39); col. 2 (Formula (I)); col. 3, ll. 24-33 (pharmaceutical compositions; therapeutic use); col. 5 (Formula (Ia)); col. 19, ll. 45-48 (methods of treating cancer); col. 35 (synthesis scheme); cols. 51, 54, 58, 60-61 (exemplified compounds). Liang, p. 4038, Table 3; p. 4039, Table 4. The rejections do not rely on facts within personal knowledge of the examiner, and no official notice has been taken. See MPEP § 2144.03.
Reiterated Rejection
Claims 1-6, 9, 11-12, 14 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Yoshino et al. (US5767283A, Published June 16, 1998) (of record, IDS dated 08/20/2025, U.S. patent cite no. 3).
Claim 1 is directed towards a compound of formula I:
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(indole or indazole-pyrazole-sulfonamides).
For example, claim 1 reads on a compound having the following structure:
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(drawn by examiner).
This is a preferred compound of the invention and has the following structure:
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(Specification, page 73).
Yoshino teaches the following compound is an antitumor agent with activity against colon cancer cells (Yoshino, Specification, column 11, Table 1-1):
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(Yoshino, Specification, column 38, lines 45-55).
One of ordinary skill in the art would expect that the compounds claimed by the Applicant would have the same properties as the compounds disclosed by Yoshino because Yoshino teaches compounds which differ from a species falling within the genus by only a single nitrogen atom (imidazole instead of pyrazole) and a genus which includes pyrazole.
Yoshino teaches a generic formula wherein imidazole in the above compound can be pyrazole:
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(Yoshino, Specification, column 1);
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(Yoshino, Specificaiton, column 2; see line 28 for pyrazole). As stated in the MPEP, such compounds are so similar that an ordinary artisan would expect similar properties:
Prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979) (Claimed and prior art compounds were both directed to heterocyclic carbamoyloximino compounds having pesticidal activity. The only structural difference between the claimed and prior art compounds was that the ring structures of the claimed compounds had two carbon atoms between two sulfur atoms whereas the prior art ring structures had either one or three carbon atoms between two sulfur atoms. The court held that although the prior art compounds were not true homologs or isomers of the claimed compounds, the similarity between the chemical structures and properties is sufficiently close that one of ordinary skill in the art would have been motivated to make the claimed compounds in searching for new pesticides.).
MPEP § 2144.09 [R-07.2022].
Furthermore, Yoshino does teach that compound 55 has in vitro antitumor activity against colon cancer cells that outperforms the control (IC50 of 0.59 for the test compound vs. 2.0 for the control CQs) (Yoshino, Specification, columns 11-12). This activity is typical of species within the disclosed genus, structurally similar to that claimed, providing a reason for one of ordinary skill in the art to choose the claimed species from the genus, based on the reasonable expectation that structurally similar species usually have similar properties. See, e.g., Dillon, 919 F.2d at 693, 696, 16 USPQ2d at 1901, 1904. See also In re Deuel, 51 F.3d 1552, 1558, 34 USPQ2d 1210, 1214 (Fed. Cir. 1995) ("Structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds. For example, a prior art compound may suggest its homologs because homologs often have similar properties and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties.")
Thus, claim 1 was prima facie obvious at the time of filing.
Claim 2 is directed towards a compound of claim 1 wherein R1 is methyl or halo. While in compound 55 shown above R1 is hydrogen, one of ordinary skill in the art would have a reasonable expectation of success to generate a compound of formula I of claim 1 wherein R1 is C1-C4 alkyl or halo because Yoshino teaches examples wherein R1 is C1-C4 alkyl or halo. For example
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: (Yoshino, Specification, col. 24)
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(Yoshino, Specification, column 31);
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(Yoshino, Specification, column 33); Therefore, claim 2 was prima facie obvious at the time of filing.
Claim 3 is directed towards the compound of claim 1 wherein R1 is methyl, chloro, or fluoro. As shown above in the rejection of claim 2, both Yoshino teaches anticancer aryl sulfonamides wherein R1 is methyl or halogen (bromo and chloro are shown above). Therefore, one of ordinary skill in the art would have a reasonable expectation of success to generate a compound of formula I of claim 1 wherein R1 is methyl, fluoro, or chloro and claim 3 was prima facie obvious at the time of filing.
Claim 4 is directed towards the compound of claim 1 wherein R1 is hydrogen. As shown in the 103 rejection of claim 1, Yoshino teaches an indole-imidazole-sulfonamide wherein R1 is hydrogen. Therefore, one of ordinary skill in the art would have a reasonable expectation of success to generate a compound of formula I of claim 1 wherein R1 is hydrogen and claim 4 was prima facie obvious at the time of filing.
Claim 5 is directed towards the compound of claim 1 wherein R2 is chloro, fluoro, or cyano. Claim 9 is directed towards the compound of claim 1 wherein R2 is cyano. In the example compounds taught by Yoshino shown in the rejections of claims 1-2 above, R2 is cyano and chloro (fluoro is also halogen so would be expected to have similar properties). Therefore, one of ordinary skill in the art would have a reasonable expectation of success to generate a compound of formula I of claim 1 wherein R2 is chloro, fluoro, or cyano and claims 5 and 9 were prima facie obvious at the time of filing.
Claim 6 is directed towards the compound of claim 1 wherein R3 is hydrogen. While Yoshino does not teach these exact substituent locations on a pyrazole, one of ordinary skill in the art would have a reasonable expectation of success to generate a compound of formula I of claim 1 wherein R3 is hydrogen because Yoshino teaches that R3 is hydrogen on the imidazole ring. For example, see compound 55 above.
Thus, claim 6 was prima facie obvious at the time of filing.
Claim 11 is directed towards a pharmaceutical composition comprising a compound of claim 1. One of ordinary skill in the art would have a reasonable expectation of success to arrive at a pharmaceutical composition comprising a compound of claim 1 because similar compositions are commonly known in the art. For example, Yoshino teaches pharmaceutical compositions:
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(Yoshino, Specification, column 2). Thus, claim 11 was prima facie obvious at the time of filing.
Claim 12 is directed towards a method of treating cancer comprising administering a therapeutically effective amount of a compound of claim 1 to a subject. One of ordinary skill in the art would have a reasonable expectation of success to treat cancer with the compound of claim 1 because similar compound are known in the art for the treatment of cancer. For example, Yoshino teaches that the compounds of their invention are effective to treat cancer:
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(Yoshino, Specification, column 2); Thus, claim 12 was prima facie obvious at the time of filing.
Claims 14 and 16-17 are directed towards the compound: N-(3-chloro-4-methyl-1H-indol-7-yl)-1-methyl-pyrazole-4-sulfonamide. This compound differs from example 55 in that the indol is substituted with chloro and methyl instead of cyano and the imidazole is substituted with pyrazole. One of ordinary skill in the art would have a reasonable expectation of success to substitute imidazole with pyrazole for the reasons given in the rejection of claim 1. One of ordinary skill in the art would have a reasonable expectation of success to substitute the indole with chloro and methyl because Yoshino teaches that these substitutions yield active compounds. For example, see Yoshino’s example 26 in the rejection of claim 2. Therefore, claims 14 and 16 were prima facie obvious at the time of filing.
Claims 1-6, 9, 11-12, 14 and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Gray et al. (US 11,807,606 B2, Published November 7, 2023, Priority Date January 25, 2018) (of record, IDS dated 08/20/2025, U.S. patent cite no. 4) in view of Liang et al. (Bioorganic & Medicinal Chemistry Letters, Vol. 26, Issue 16, 15 August 2016, p. 4036-4041) (of record, IDS dated 08/20/2025, NPL cite no. 2).
Claim 1 is directed towards a compound of formula I:
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(indole or indazole-pyrazole-sulfonamides). For example, compounds of formula I include
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(Specification, p. 79) and
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(Specification, p. 75).
Grey teaches RBM39 degrading compounds with anticancer activity of general formula (I) and (Ia):
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Formula (I) (Grey, Specification, col. 2) and
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Formula (Ia) (Grey Specification, col. 5).
For example, Grey teaches the RBM39 degrading compound
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(Grey, Specification, col. 58).
While Grey’s compound differs from the instantly claimed compounds in that the sulfonamide is linked to chlorophenyl instead of 2-cyanoethyl-pyrazole or ethyl-pyrazole, one of ordinary skill in the art would have a reasonable expectation of success to substitute 2-cyanoethyl-pyrazole or ethyl-pyrazole because these groups are known in the art to have similar properties to chlorophenyl.
For example, see Liang who teaches that these substituents produce compounds with similar activities:
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Liang, p. 4038;
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Liang, p. 4039.
Therefore, claim 1 was prima facie obvious at the time of filing.
Claims 2-3 and 5-10 read on the compounds shown above and were thus prima facie obvious at the time of filing.
Claim 4 is directed towards a compound of claim 1, wherein R1 is hydrogen. One of ordinary skill in the art would have a reasonable expectation of success to generate an RBM39 degrader wherein R1 is hydrogen because Grey teaches that R1 may be hydrogen. For example,
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(Grey, Specification, col. 54, compound 31).
Therefore, claim 4 was prima facie obvious at the time of filing.
Claim 11 is directed towards a pharmaceutical composition comprising a compound of claim 1. One of ordinary skill in the art would have a reasonable expectation of success to arrive at a pharmaceutical composition comprising a compound of claim 1 because similar compositions are commonly known in the art. For example, Grey teaches pharmaceutical compositions: “In certain embodiments, disclosed herein are pharmaceutical compositions comprising a compound of Formula (І), Formula (II), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.” (Grey, Specification, col. 3, lines 29-33). Therefore, claim 11 was prima facie obvious at the time of filing.
Claim 12 is directed towards a method of treating cancer comprising administering a therapeutically effective amount of a compound of claim 1 to a subject. One of ordinary skill in the art would have a reasonable expectation of success to treat cancer with the compound of claim 1 because similar compound are known in the art for the treatment of cancer. For example, Grey teaches that the compounds of their invention are effective to treat cancer:
In certain embodiments, disclosed herein are compounds of Formula (I) or Formula (II) that act as degraders of RRM proteins. These compounds are therapeutic agents for the treatment of diseases such as cancer and metastasis, and other RRM protein mediated diseases.
Grey, Specification, col. 3, lines 24-29;
In certain embodiments the disclosure relates to a method of treating or preventing cancer, comprising administering to a subject in need thereof of a compound of Formula (I), Formula (II), or a pharmaceutically acceptable salt thereof.
Grey, Specification, col. 19, lines 45-48.
Therefore, claim 12 was prima facie obvious at the time of filing.
Claims 14, 16 and 17 are directed towards the compound 1-(2-cyanoethyl)-N-(3-cyano-4-methyl-1H-indol-7-yl) pyrazole-4-sulfonamide. This compound is shown and rejected in the rejection of claim 1, incorporated herein by reference. Therefore, claims 14 and 16-17 were prima facie obvious at the time of filing.
Given the above teachings, the invention as a whole was prima facie obvious at the time of filing.
Claim Objections – Dependent upon Rejected Base Claim
Claim 15 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.
Conclusion
No claim is found to be allowable.
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 extension fee 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.
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/HEATHER DAHLIN/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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