DETAILED ACTION
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 1, 3, 5, 8, 12, 15, 19, 22, 25, 26, 28, 31, 32, 50, 51, 53, 57, 58, 61, 63, 64, 78, 79, 82-94 are pending. Claims 2, 4, 6, 7, 9-11, 13, 14, 16-18, 20, 21, 23, 24, 27, 29, 30, 33-49, 52, 54-56, 59-60, 62, 65-77, 80, and 81 are cancelled.
Status of Priority
The present application is a 35 U.S.C. § 371 national stage patent application of International patent application PCT/CN2021/121023, filed on September 27, 2021. This application also claims the benefits of foreign priority to CN202110905531.5, filed on August 05, 2021 and CN202011044828.9 filed on September 28, 2020.
Specification - Disclosure
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claims 12, 31, 32, and 92 are objected to because of the following informalities:
In claim 12, to be consistent with the claim it is dependent upon (i.e., claim 1):
“-NHC(O)(R1b)” should read “-NHC(O)(R1c)”
“-NHSO2(R1b)” should read “-NHSO2(R1c)”
Claim 31 discloses a structure represented by formula (II-e) as reproduced below:
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and states that R2a-1 is as defined by R2a in claim 1. However, in the most recent amended claim set (filed December 15, 2025), the R2a variable has been deleted from claim 1. As such, “(R2a-1)m2-1” can be removed from the structure of formula II-e to be consistent with claim 1 and for clarity.
Claim 32 discloses a structure represented by formula (II-e1) as reproduced below:
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and states that R2a-2 is as defined by R2a in claim 1. However, in the most recent amended claim set (filed December 15, 2025), the R2a variable has been deleted from claim 1. As such, “(R2a-2)m2-2” can be removed from the structure of formula II-e1 to be consistent with claim 1 and for clarity.
Also in claim 32, for completeness, the following phrase should be added in the description corresponding to the structure represented by formula (II-d6):
“R2x-1 is as defined by R2x in claim 1”
In claim 92, there are currently three alternatives listed. There should be an “or” between the first and second alternatives.
Appropriate correction is required.
Added Rejections
Claim Rejections - 35 USC § 112(a) – Enablement
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 86, 87, and 91-94 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
As stated in the MPEP 2164.01(a), “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.”
In evaluating the enablement question, several factors are to be considered. According to In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988), these factors include:
1) The nature of the invention,
2) the state of the prior art,
3) the predictability or lack thereof in the art,
4) the amount of direction or guidance present,
5) the presence or absence of working examples,
6) the breadth of the claims, and
7) the quantity of experimentation needed, and
8) the level of the skill in the art.
In the instant case, the Wands factors are relevant for the following reasons:
The nature of the invention
The nature of the invention claims a class of fused ring compounds that have a structure represented by formula (I’):
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and are compounds that can significantly inhibit the ataxia-telangiectasia mutated (ATM) kinase activity, exhibit good selectivity for the ATM target, and are useful for treating cancer.
The variables of general formula (I’) are defined in instant claim 1.
State of the prior art
According to an STN search, there is no prior art disclosing a compound with a structure represented by instant formula (I’). Thus, the instant compounds represented by instant formula (I’) are considered novel. As such, there are no prior art disclosing methods for treating any cancer or any disease and/or disorder which is partially mediated by ATM kinase by administering the instant compounds represented by formula (I’) to a subject in need thereof.
The level of the skill in the art
The level of ordinary skill in the art is relatively high. A person of ordinary skill would typically have formal training in oncology, medicinal chemistry, and organic synthesis and would be familiar with standard methods for evaluating therapeutic efficacy.
The presence or absence of working examples
The instant specification provides results from in vivo studies investigating:
the efficacy of the compounds of the present disclosure combined with irinotecan liposome injection on inhibiting the growth of subcutaneous xenograft tumor of human non-small cell lung cancer cell line NCI-H441 (starting on pg. 220, para. 001076)
the efficacy of the compounds of the present disclosure combined with irinotecan liposome injection on inhibiting the growth of subcutaneous xenograft tumor of human colon cancer cell line HT-29 (starting on pg. 222, para. 001086)
the efficacy of the compounds of the present disclosure combined with radiotherapy in the intracranial murine glioma GL-261-Luc model (starting on pg. 224, para. 001096) and
the efficacy of the compounds of the present disclosure combined with radiotherapy on inhibiting the growth of subcutaneous xenograft tumor of human glioblastoma LN-18 (starting on pg. 226, para. 001113).
According to MPEP § 2163:
“Satisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the inventor was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’ Such correlations may be established ‘by the inventor as described in the specification,’ or they may be ‘known in the art at the time of the filing date.’ See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014).
Even though the instant specification provides working examples of the instant compounds (represented by formula (I’)) being used to treat some cancers (i.e., non-small cell lung cancer, colon cancer, intracranial murine glioma, and glioblastoma) in animal models, there are no additional working examples of the instant compounds (represented by formula (I’)) being used to treat all other cancer or all other disease and/or disorder (which is at least partially mediated by ATM kinase) that are not covered in the instant specification.
The amount of direction or guidance present and quantity of experimentation necessary
In the absence of clear guidance, a person of ordinary skill in the art would require undue experimentation to test the efficacy of the compounds of the present disclosure in treating all other cancers or all other diseases and/or disorders (which is at least partially mediated by ATM kinase) that are not covered in the instant specification.
The breadth of the claims
The claims are broad insofar as the instant claims recite a method of treating a cancer or a disease and/or disorder which is at least partially mediated by ATM kinase, each of which further comprises numerous distinct disease entities.
Claims 87, 92, and 94, which are dependent on claims 86, 91, and 93, respectively, are also rejected for further requiring and/or reciting non-enabling elements as explained above.
Rejections necessitated by the amended claims
Claim Rejections - 35 USC § 112(a) – Written description
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claim 83 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 83 is directed towards intermediate compounds and includes the negative limitation “provided that the intermediate is not
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.” The specification, however, does not reasonably convey to a person of ordinary skill in the art that Applicant was in possession of the claimed subject matter including this exclusion at the time of filing. Accordingly, the negative limitation lacks adequate written description support.
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.
Claim 12 is 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.
In the last three lines of claim 12, it states that R1a can be -OCH3 or -OCH2CH3. Claim 12 is dependent on claim 1 which no longer allows R1a to be an alkoxy group. Since, claim 12 is broadening the scope of claim 1, it is thus written in an improper dependent form.
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.
Note on 35 USC § 102 and § 103 Rejections
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 § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim 83 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by an STN entry entered on August 8, 2011:
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According, to the entry, the compound can be purchased from Princeton BioMolecular Research, Inc. as of August 08, 2011. This compound is a compound represented by Formula (M-1) wherein:
L = CH
R4 = F; h = 1
Rx1 = H
A:
Q1 = Q3 = C
n2 = t5 = t6 = 0 (i.e., Q2, R12, and R13 are absent)
R8 = R9 = R10 = R11 = hydrogen (t3 = t4 = 1)
W = O
t1 = t2 = 0 (i.e., R6 and R7 are absent)
Allowable Subject Matter
Claims 1, 3, 5, 8, 15, 19, 22, 25, 26, 28, 50, 51, 53, 57, 58, 61, 63, 64, 78, 79, 82, 84, 85, 88, 89, and 90 are allowed. Claims 31 and 32 are objected to, but would be allowable once the corresponding appropriate corrections are made.
Conclusion
Claims 1, 3, 5, 8, 15, 19, 22, 25, 26, 28, 50, 51, 53, 57, 58, 61, 63, 64, 78, 79, 82, 84, 85, 88, 89, and 90 are allowed. Claims 31 and 32 are objected to. Claims 12, 83, 86, 87, and 91-94 are rejected. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTEN ROMERO whose telephone number is (571)272-6478. The examiner can normally be reached M-F 9:30 AM - 6:00 PM ET.
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/KRISTEN W ROMERO/Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624