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 .
Current Status
This action is responsive to the amended claims of 06/30/2023. Claims 1-10 and 17-20 are pending. Claims 1-10 and 17-20 have been examined on the merits.
Note, no restriction/election requirement has been put in place.
Priority
The effective filing date is 12/31/2020.
Information Disclosure Statement
Please note, as of 10/07/2025, no information disclosure statement (IDS) has been submitted.
Claim Objections
Claims 1-10 and 17-20 are objected to because of the following informalities. Appropriate correction is required:
In claims 1-3, please make sure there is a comma after the second to last option in every list of 3 or more. For example, there is a comma lacking after X3 in the recitation of “X1, X2, X3 and X4” and after “-C(O)CH2NHC(O)-” in the definition of R2. Dependent claims 4-10 and 17-20 are similarly objected to since they do not rectify the issue.
In claims 1-3, the variable R1 is defined as –(CH)nX-R2. Under general chemical guidelines, the artisan would understand the CH, having only 3 defined bonds in the structure of Formula (I), to be bound to an implicit second H. To improve the form of the claim, Examiner suggests replacing “–(CH)nX-R2” with “–(CH2)nX-R2”. Dependent claims 4-10 and 17-20 are similarly objected to since they do not rectify the issue.
In claim 3, the variable R1 of Formula (I) is replaced with R1. The variable R1 is chosen from the same moieties as R1, thus, the discrepancy in subscripted vs. superscripted numeral does not cause any indefiniteness issues. However, to improve consistency of variable labeling between claims, Examiner suggests Applicant replace R1, in both the structure of (IV) and the accompanying claim text, with R1 as seen in genus Formula (I).
In claim 3, at the end of the limitation defining X, please replace “-C(O)NH-,” with “-C(O)NH-; and”. This improves grammar and is consistent with the formatting of the other claims.
In claim 5, compound 8 appears to be a duplicate of compound 7. Please remove the duplicated structure since it is redundant.
Claim Rejections - 35 USC § 112(b)
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 2-3 and 5 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.
Claim 2 recites the limitation "Ra is -H or C1-6 alkyl". There is insufficient antecedent basis for this limitation in the claim, in particular Ra is C5-6 alkyl. Antecedent claim 1 recites “Ra is -H or C1-4 alkyl", but does not recite wherein Ra is C5-6 alkyl. Thus, the scope of Ra is unclear and the metes and bounds of the claim are undefined rendering the claim indefinite.
To overcome: please replace C1-6 alkyl with C1-4 alkyl.
Claim 3 recites the variable Rm in Formula (IV) and the variables R and m in the accompanying claim text. Since Rm is recited wherein m is a subscript of R (i.e.,
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), there is a lack of continuity between the annotation in the Formula (IV) and the claim text. The claim text does not recite Rm and the Formula (IV) does not recite the variable R and the separate variable m; i.e., there is an internal lack of antecedent basis. It is unclear based on this discrepancy between Formula (IV) and the text whether the variable here
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should be interpreted as R and m or as Rm. Moreover, in the case that the variable is Rm, the claim text does not define a variable Rm making the chosen moieties unclear. Further, parent claim 1 does not recite the variable Rm and since claim 3 does not define the variable Rm, there is a lack of antecedent basis for the variable Rm. Thus, the metes and bounds of the claim are undefined rendering the claim indefinite.
To overcome: if Applicant meant for the variable Rm to represent variable R is present m times, please draw the variable as (R)m.
Claim 5 recites seven compounds which lack antecedent basis in the claim. Compounds 3-6 and 9-11 recite moieties which are outside of the scope of antecedent claim 1, as follows:
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in compound 3 B cannot be CH(Me) since Formula (I) states B is CH2;
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in compound 4 and
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in compound 9 the bonding between the core and the phenyl-piperazine moiety is incorrect and should occur at the asterisk annotation;
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in compound 5 the bonding between the phenyl and piperazine moiety is incorrect and should occur at the asterisk annotation;
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in compound 6 R1 cannot be Me based on the definition of R1 in Formula (I);
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in compound 10 the annotated N should be a Carbon and R1 cannot be Me per the structure of Formula (I); and
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in compound 11 the annotated N should be a Carbon per the structure of Formula (I). Since the structures of compounds 3-6 and 9-11 lack antecedent basis, the metes and bounds of claim 5 are undefined rendering the claim indefinite.
To overcome: Applicant could amend claim 5 to be independent.
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 2-3 and 5 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.
Claim 2 recites the limitation "Ra is -H or C1-6 alkyl”. Parent claim 1 recites “Ra is -H or C1-4 alkyl", but does not recite wherein Ra is C5-6 alkyl. Thus, the scope of Ra as defined in claim 2 is broader than the scope defined in claim 1. Therefore, claim 2 does not further limit claim 1.
Claim 3 recites the variable Rm in Formula (IV). Parent claim 1 does not recite the variable Rm. Since claim 3 does not define the variable Rm, the scope of the variable Rm is unknown. Therefore, claim 3 does not properly further limit parent claim 1.
Claim 5 recites compounds 3-6 and 9-11 which contains moieties that are outside of the scope of parent claim 1 (see paragraph 16 for a detailed explanation of the pertinent moieties). Thus, the compounds 3-6 and 9-11 of claim 5 do not further limit the parent claim 1.
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.
To overcome: please see the corresponding 35 USC 112(b) rejections, above, for suggestions to overcome.
Conclusion
Claims 2-3 and 5 are rejected.
Claims 1, 4, 6-10, and 17-20 are objected to.
A search for the compound of Formula (I) and the compounds of claim 5 did not return any prior art (see SEARCH 6 of the attached search notes). The closest art may be considered LEE (WO 2006/044933), ZHU (WO 2016/140971), LEE (WO 2007/120726), and BUDKE (Budke, B. et al. ChemMedChem, 2019, 14, 1031-1040).
LEE (2006) teaches RAD51 inhibitors (Pg. 2 line 28-30) such as the compound
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(Pg. 31 claim 5) which lacks the instant moiety
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at the annotated arrow. ZHU teaches RAD51 inhibitors (abstract) such as
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and
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(Pg. 5) which also lacks the same instant moiety as the compound of LEE. Neither LEE nor ZHU teach any RAD51 inhibitor compounds with the instant moiety
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and neither reference provides any teaching-suggestion-motivation to add the instant moiety to the RAD51 inhibitor compounds. LEE (2007; cited by the EPO in the Global Dossier) teaches a genus Formula
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(Pg. 3) and the scheme
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(Pg. 21 Scheme 3) wherein both bicycles may be substituted by a variety of moieties (some are drawn out but the inclusion of “etc.” broadens this scheme to the full scope of Formula 1 as it pertains to R1 and R2). LEE (2007) only teaches 3 species of the Formula 1 (redrawn here for clarity)
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,
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, and
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(Pg. 9 1A, 1B, & 1C). Each of 1A-1C lacks the instant moiety
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. While 1C contains a moiety which falls under the definition of the instant cycle containing A and B, the moiety is attached at a completely different position on the core structure. Further LEE (2007) only provides pharmacological data for compound 1A as a RAD51 inhibitor (Pg. 22 last para), thus, it is not shown whether other compounds encompassed by the large genus Formula 1 display the ability to inhibit RAD51. Since LEE (2007) only teaches 1 species wherein an analogous moiety to the instant moiety
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is present but is not substituted on the benzylsulfonyl-bearing cycle at the instantly claimed position and since LEE (2007) only provides data for a compound which completely lacks the analogous moiety (1A), there is no teaching-suggestion-motivation for the artisan to make the instant substitution. The teachings of LEE (2007) provide no evidence that the substitution of the instant moiety on the benzylsulfonyl-bearing cycle at the instantly claimed position would provide any pharmacological benefit. Furthermore, BUDKE provides a review of drug candidates that inhibit RAD51:
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(Pg. 1039 Fig. 6) wherein 41-43, 45-46, and 2h all have 2+ structural differences from the instant compounds and 44 is equivalent to compound 1A of LEE (2007). Thus, even in view of the contemporary art (i.e., BUDKE, LEE (2006), and ZHU), the artisan would not find any motivation to make the necessary substitution to arrive at the instant compounds from LEE (2007). To do so, the artisan would have to engage in picking and choosing of both chemical moiety and attachment point likely led by hindsight reasoning.
Finally, the instant disclosure provides evidence of superior results when comparing exemplary compounds of instant Formula (I) to the prior art compound IBR120 (i.e., 1A of LEE (2007)). As seen on Pg. 34 of the specification, Examples 14 and 15 (para 140-141) state that the instant compounds have superior activity to IBR120 in the inhibition of NSCLC cell line (Ex. 14) and pancreatic cancer cell line (Ex. 15). Figures 14 and 15 in the instant drawings clearly show the relative cell density is lower in the samples treated with the instant compounds compared to the prior art compound IBR120. Thus, Examiner understands superiority of a property shared with the prior art (i.e., anti-cancer activity) as evidence of nonobviousness (see MPEP 716.02(a)(II)).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARA ELIZABETH BELL whose telephone number is (703)756-5372. The examiner can normally be reached Monday-Friday 9:00-5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew Kosar can be reached at 571-272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/S.E.B./Examiner, Art Unit 1625
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625