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 .
Status of the Claims
The listing of claims filed 30 April 2024 has been reviewed.
Claims 13-28 are pending.
Claims 13-28 are newly added.
Claims 1-12 are cancelled.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) filed on 02 August 2024 and 22 May 2026 are acknowledged and have been considered.
Priority
The instant application was received 30 April 2024; it is a national stage application of PCT/CN2022/128588, filed 31 October 2022, and claims priority to CN202111375858.2, filed 19 November 2021, and CN202111281363.3, filed 01 November 2021. Acknowledgment is made of Applicant’s claim for foreign priority and a certified copy of the priority document has been received.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because it contains legal phraseology, specifically the term “comprising.” A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
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.
Claim 16 is 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 16 recites the variables “R3b”, “R3c”, and “R3d”. Claim 13, upon which claim 16 depends, recites, “A compound of formula (III)…” and provides the chemical structure. However, the variables “R3b”, “R3c”, and “R3d” are absent from claim 13. Therefore, it is unclear what structures or groups are being referred to by these variables.
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 22 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.
Claim 13, upon which claim 22 depends, recites, “…X5 and X6 are independently selected from CR6 or N, and X5 and X6 are not both CR6 or N…” (emphasis added). However, both X5 and X6 are CR6 in some of the instantly claimed compounds recited by claim 22. For example, in Compound 1 (p. 7, Claim 22) X5 and X6 are both CH (i.e., R6 is H). Thus, claim 22 does not further limit claim 13 because claim 22 improperly expands the scope of claim 13 to include compounds wherein both X5 and X6 are CR6. Additionally, in Compound 4 the S in the structure recited by claim 13 is replaced by O. Therefore, claim 22 also does not further limit claim 13 because claim 22 improperly expands the scope of claim 13 to include compounds wherein the S in the structure recited by claim 13 is instead O.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
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.
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Chuanfei (CN 111943960 A; IDS dated 02 August 2024, Cite No. 3) in view of Nogueira (Nogueira et al., “New FDA oncology small molecule drugs approvals in 2020: Mechanism of action and clinical applications,” Bioorganic & Medicinal Chemistry 46 (2021) 116340, p. 1-28).
Regarding claim 22, Chuanfei teaches compounds and pharmaceutical compositions for treating sex hormone-dependent diseases, said compounds being substituted pyrimidinedione compounds which are used as gonadotropin-releasing hormone receptor antagonists (p. 1, Technical Field). The core structure is represented by formula (I), shown below, wherein Z can be NRn, S, or O (p. 2):
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Exemplary compounds disclosed by Chuanfei having the same core structure as shown above include 1-(4-(3-(6-(1H-pyrazol-1-yl) pyridazin-3-yl)-1-(2,6-difluorobenzyl)-5-((dimethylamino) methyl) -2,4-dioxo -1,2,3,4 tetrahydrothieno [2,3-d] pyrimidin-6-yl) phenyl)-3-methoxyurea (p. 20, Example 12):
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Note, the compound shown above is structurally similar to instantly claimed Compound 4, but differs since it has an added pyrazole substitution and the O in Compound 4 is instead an S in the compound disclosed by Chuanfei.
Chuanfei does not explicitly teach an instantly claimed compound recited by claim 22.
Nogueira teaches Relugolix, also called TAK-385, Orgovyx, or Relumina, was approved in 2020 and has the following structure (p. 19, Col. 2, 5. Hormone antagonist; p. 20, Fig. 20):
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Relugolix is a selective gonadotropin-releasing hormone receptor antagonist (p. 20, Col. 1, ¶ 1). Furthermore, Nogueira indicates Relugolix could be used in treating various sex-steroid dependent diseases and disorders including endometriosis, uterine fibroids, hirsutism, dysfunctional uterine bleeding, premenstrual syndrome, precocious puberty, assisted reproduction, prostate cancer, leiomyoma, and breast cancer (p. 20, Col. 1-2).
Nogueira does not explicitly teach an instantly claimed compound recited by claim 22.
Prior to the filing of the instant application, a person having ordinary skill in the art (PHOSITA) following the teachings of Chuanfei would have found it prima facie obvious to prepare an instantly claimed compound recited by claim 22 based on the teachings of Nogueira because Chuanfei indicates the position corresponding to S in Relugolix could be O. Thus, a PHOSITA would have had a reasonable expectation of success in modifying the structure of Relugolix based on the teachings of Chuanfei because structurally similar compounds generally have similar activity, so a PHOSITA would have been motivated to change the S in Relugolix to O in search of analogs having similar activity due to the clinical success of Relugolix in Japan for treating uterine fibroids and in the US for treating prostate cancer (Nogueira, p. 20, Col. 2).
Allowable Subject Matter
Claims 13-15, 17-19, and 23-28 are allowed. None of the prior art of record nor a search in the pertinent art area teaches a compound of formula (III) or a pharmaceutically acceptable salt or stereoisomer thereof.
Regarding claims 13-15, 17-19, and 23-28, the following is a statement of reasons for the indication of allowable subject matter:
The claimed compound has the structure of formula (III):
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Wherein:
X5 and X6 are independently selected from CR6 or N, and X5 and X6 are not both CR6 or N;
R1 is independently selected from H, D, C1-C6 alkyl, C3-C6 cycloalkyl, and C1-C6 haloalkyl;
R2 is independently selected from H, D, C1-C6 alkyl, and C1-C6 substituted with R2a-O-;
R2a is independently selected from C1-C6 haloalkyl;
R3a and R3e are each independently selected from H, D, halogen, C1-C6 alkyl, C1-C6 haloalkyl, and C3-C6 cycloalkyl;
R4 is independently selected from H, D, halogen, -CN, -NO2, -NH2, -OH, -SH, -COOH, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 alkylamino, and C3-C6 cycloalkyl;
R5 is independently selected from H, D, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C3-C6 cycloalkoxy, and C1-C6 haloalkoxy;
R6 is independently selected from H, D, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy.
The closest prior art is Chuanfei (CN 111943960 A; IDS dated 02 August 2024, Cite No. 3) and Bestel (WO 2021/023877 A2; IDS dated 02 August 2024, Cite No. 8). Shown below are exemplary compounds disclosed by Chuanfei and Bestel, which share some structural similarities with the instantly claimed compounds:
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Chuanfei (p. 20, Example 12) Bestel (p. 213, Compound 83)
The instantly claimed compounds differ from those disclosed by Chuanfei and Bestel in the following respects:
In the instantly claimed compounds, R4 can be H, D, halogen, -CN, -NO2, -NH2, -OH, -SH, -COOH, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 alkylamino, or C3-C6 cycloalkyl. However, in the compound disclosed by Chuanfei the group corresponding to R4 is pyrazole.
In the instantly claimed compounds, X5 and X6 can be either CR6 or N, but X5 and X6 cannot both be CR6 or N. In the compounds disclosed by Chuanfei and Bestel, X5 and X6 are both C, wherein R6 is H.
Thus, while Chuanfei’s and Bestel’s compounds share some structural similarities with the instantly claimed compounds, a skilled artisan would not have been motivated to make the aforementioned changes as a whole to the structures which would have resulted in the instantly claimed compounds. Specifically, the prior art contains no suggestion to change a C in the same position as either X5 or X6 to N.
Claims 20-21 are allowed. None of the prior art of record nor a search in the pertinent art area teaches a compound of formula (II) or a pharmaceutically acceptable salt or stereoisomer thereof.
Regarding claims 20-21, the following is a statement of reasons for the indication of allowable subject matter:
The claimed compound has the structure of formula (II):
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Wherein:
X1 is independently selected from O or S;
X2 and X3 are each independently selected from CR4 or N;
X5 is independently selected from CH or N;
R1 is independently selected from H, D, and C1-C6 alkyl;
R2 is independently selected from the following groups substituted with R2a-O-: methyl, ethyl, n-propyl, and n-butyl;
R2a is independently selected from fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, and trichloromethyl;
R3a and R3e are each independently selected from H, D, fluorine, chlorine, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, and trichloromethyl;
R4 is independently selected from H, D, fluorine, chlorine, methoxy, ethoxy, n-propoxy, n-butoxy, fluoromethoxy, chloromethoxy, difluoromethoxy, dichloromethoxy, trifluoromethoxy, trichloromethoxy, methylthio, ethylthio, n-propylthio, n-butylthio, methylamino, ethylamino, n-propylamino, and n-butylamino;
R5 is independently selected from H, D, methyl, ethyl, n-propyl, n-butyl, methoxy, ethoxy, n-propoxy, and n-butoxy.
The closest prior art is Cho (WO 2004/067535 A1). Shown below is an exemplary compound disclosed by Cho (p. 98), which shares some structural similarities with the instantly claimed compounds:
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The instantly claimed compounds differ from those disclosed by Cho in the following respects:
In the instantly claimed compounds, R2 is R2a-O-substituted methyl, ethyl, n-propyl, or n-butyl wherein R2a is fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, and trichloromethyl. However, in the compound disclosed by Cho, R2 is Me-O-Et- and does not contain any halogen atoms.
In the instantly claimed compounds, X5 can be either CR4 or N. Cho does not suggest changing the C in this position to N.
Thus, while Cho’s compound shares some structural similarities with the instantly claimed compounds, a skilled artisan would not have been motivated to make the aforementioned changes as a whole to the structures which would have resulted in the instantly claimed compounds. Specifically, the prior art contains no suggestion to change a C in the same position as X5 to N neither does the prior art suggest R2 is a haloalkyl-O-alkyl- group where the haloalkyl is fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, or trichloromethyl.
Conclusion
Claims 13-15, 17-21, and 23-28 are allowed.
Claims 16 and 22 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIANNA L BAUER whose telephone number is (571)272-5752. The examiner can normally be reached 8am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, ADAM C MILLIGAN can be reached at (571)270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/B.L.B./Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
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