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 .
Priority
The instant application, filed 09/12/2023, is a national stage entry of PCT/US2022/020230, filed 03/14/2022, which claims domestic priority to provisional U.S. application number 63288965, filed 12/13/2021, and 63160436, filed 03/12/2021.
Preliminary Amendments and Claim Status
The preliminary amendment filed on 04/22/2024 is acknowledged and entered.
Claims 3-5, 7, 8, 11, 15-17, and 25-28 are amended;
Claims 6, 9, 10, 12-14, 18, 19, and 24 are cancelled;
Claims 1-5, 7, 8, 11, 15-17, 20-23, and 25-28 are pending and are under prosecution.
Information Disclosure Statement
The Information Disclosure Statement filed on 03/20/2025 is acknowledged and found to be in compliance with the provisions of 37 CFR § 1.97. Accordingly, the information disclosure statement is considered.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered. For example, paragraph [0167] (and other paragraphs throughout the specification) includes references not listed in the information disclosure statement.
Specification
The disclosure is objected to because of the following informalities:
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (e.g., see page 1 of the instant specification). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code . See MPEP § 608.01.
Appropriate correction is required.
Claim Rejections - 35 U.S.C. § 112
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 1-5, 7, 8, 11, 15-17, 20-22, and 25-28 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 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.
Claims 1-5, 7, 8, 11, 15-17, 20-22 and 25-28 of the instant application are drawn to compounds having following substituents:
R1 is aryl or heteroaryl, wherein the aryl and the heteroaryl are optionally substituted with one, two, three, four, or five substituents independently selected from C1-C3alkyl, C2-C4alkenyl, C2-C4alkynyl, amino, aminoC1-C3alkyl, C3-C4cycloalkyl, halo, haloC1-C3alkoxy, haloC1-C3alkyl, hydroxy, and hydroxyC1-C3alkyl;
PNG
media_image1.png
2
9
media_image1.png
Greyscale
PNG
media_image1.png
2
9
media_image1.png
Greyscale
PNG
media_image1.png
2
9
media_image1.png
Greyscale
(of Formula (I))
R2 is hydrogen, C1-C3alkoxy, C1-C3alkyl, cyano, halo, haloC1-C3alkyl, and hydroxy; R2 as C1-C3alkoxy, C1-C3alkyl, cyano, fluoro, bromo, iodo, haloC1-C3alkyl, and hydroxy;
R3 is hydrogen, C1-C3alkoxy, C1-C3alkyl, cyano, halo, haloC1-C3alkyl, and hydroxy; R2 as hydrogen, C1-C3alkoxy, C1-C3alkyl, cyano, chloro, bromo, iodo, haloC1-C3alkyl, and hydroxy;
Ra is hydrogen or C1-C3alkyl;
n is 0, 1, 2, 3, or 4;
Rb is C1-C3alkyl, C3-C6cycloalkyl, halo, and hydroxy; or, alternatively, two geminal Rb groups, together with the carbon atom to which they are attached, can form a 3- to 6-membered cycloalkyl ring;
R5 is —(C1-C3alkyl)-R6 or —(C1-C6alkyl)NRcRd wherein Rc and Rd, together with the nitrogen atom to which they are attached, form a five to ten-membered ring monocyclic or bicyclic ring optionally containing one additional heteroatom selected from nitrogen, oxygen, and sulfur, wherein the ring is optionally substituted with one, two, or three groups independently selected from C1-C3alkoxy, C1-C3alkoxyC1-C3alkyl, C1-C3alkyl, benzyl, halo, haloC1-C3alkyl, hydroxy, hydroxyC1-C3alkyl, and oxo; or one of Rc and Rd is selected from hydrogen and C1-C3alkyl and the other is selected from hydrogen, C1-C3alkyl, C1-C3alkoxycarbonyl, and C1-C3alkylcarbonyl, and
PNG
media_image2.png
83
51
media_image2.png
Greyscale
;
R6 is selected from: a C3-C6cycloalkyl substituted with NRcRd(C1-C3alkyl); and a five- to ten-membered monocyclic, bicyclic, or tricyclic ring containing one nitrogen atom and optionally a second heteroatom selected from oxygen or nitrogen, wherein the ring contains zero to three double bonds and wherein the ring is optionally substituted with one, two, or three groups independently selected from C1-C3alkoxy, C1-C3alkyl, halo, haloC1-C3alkoxy, haloC1-C3alkyl, and hydroxy;
35 U.S.C. § 112(a) and the first paragraph of pre-AIA 35 U.S.C. § all112 require that the "specification shall contain a written description of the invention ...." This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc); Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1560, 19 USPQ2d 1111,1114 (Fed. Cir. 1991); see also Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920-23, 69 USPQ2d 1886, 1890-93 (Fed. Cir. 2004) (discussing the history and purpose of the written description requirement); In re Curtis, 354 F.3d 1347, 1357, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004) ("conclusive evidence of a claim’s enablement is not equally conclusive of that claim’s satisfactory written description"). The written description requirement has several policy objectives. "[T]he ‘essential goal’ of the description of the invention requirement is to clearly convey the information that an applicant has invented the subject matter which is claimed." In re Barker, 559 F.2d 588, 592 n.4, 194 USPQ 470, 473 n.4 (CCPA 1977). Another objective is to convey to the public what the applicant claims as the invention. See Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1566, 43 USPQ2d 1398, 1404 (Fed. Cir. 1997), cert, denied, 523 U.S. 1089 (1998). "The ‘written description’ requirement implements the principle that a patent must describe the technology that is sought to be patented; the requirement serves both to satisfy the inventor’s obligation to disclose the technologic knowledge upon which the patent is based, and to demonstrate that the patentee was in possession of the invention that is claimed." Capon v. Eshhar, 418 F.3d 1349, 1357, 76 USPQ2d 1078, 1084 (Fed. Cir. 2005). Further, the written description requirement promotes the progress of the useful arts by ensuring that patentees adequately describe their inventions in their patent specifications in exchange for the right to exclude others from practicing the invention for the duration of the patent’s term.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Amer. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaffv. Wells Bees., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); EliLilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm.,927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991). An application specification may show actual reduction to practice by describing testing of the claimed invention.
In the present case, the important factors leading to a conclusion of inadequate written description is the absence of any working example of the invention as claimed, and the lack of predictability in the art.
In the instant specification, there is no disclosure of compounds having the following claimed substituents:
R1 as heteroaryl, wherein the heteroaryl is substituted with four, or five substituents independently selected from C3alkyl, C2-C4alkenyl, C3-C4alkynyl, aminoC1-C3alkyl, C3-C4cycloalkyl, halo, haloC2-C3alkoxy, haloC2-C3alkyl, and hydroxyC1-C3alkyl;
R2 as C1-C3alkoxy, C1-C3alkyl, cyano, fluoro, bromo, iodo, haloC1-C3alkyl, and hydroxy
R2 as hydrogen, C1-C3alkoxy, C1-C3alkyl, cyano, chloro, bromo, iodo, haloC1-C3alkyl, and hydroxy
Ra as C1-C3alkyl
n as 1, 2, 3, or 4
Rb as C1-C3alkyl, C3-C6cycloalkyl, halo, and hydroxy; or, alternatively, two geminal Rb groups, together with the carbon atom to which they are attached, can form a 3- to 6-membered cycloalkyl ring
R5 as —(C2-C3alkyl)-R6 or —(C2-C6alkyl)NRcRd wherein Rc and Rd, together with the nitrogen atom to which they are attached, form a five to ten-membered ring monocyclic or bicyclic ring optionally containing one additional heteroatom selected from sulfur, wherein the ring is optionally substituted with one, two, or three groups independently selected from C2-C3alkoxy, C1-C3alkoxyC1-C3alkyl, C2-C3alkyl, benzyl, halo, haloC1-C3alkyl, hydroxy, hydroxyC1-C3alkyl, and oxo; or one of Rc and Rd is selected from hydrogen and C2-C3alkyl and the other is selected from hydrogen, C1-C3alkyl, C1-C3alkoxycarbonyl, and C1-C3alkylcarbonyl or R5 as
PNG
media_image2.png
83
51
media_image2.png
Greyscale
R6 is selected from: a C4-C6cycloalkyl substituted with NRcRd(C1-C3alkyl); and a five- to ten-membered monocyclic, bicyclic, or tricyclic ring containing one nitrogen atom and optionally a second heteroatom selected from oxygen or nitrogen, wherein the ring contains one to three double bonds and wherein the ring is optionally substituted with two or three groups independently selected from C1-C3alkoxy, C2-C3alkyl, Chloro, Bromo, Iodo, haloC1-C3alkoxy, haloC1-C3alkyl, and hydroxy;
The instant specification (pages in 44-123) teaches compounds which are characterized as having only the following substituents:
R1 is aryl wherein the aryl is optionally substituted with one, two, or three substituents selected from C1-C2alkyl, C2alkynyl, amino, Fluoro, haloC1alkyl, hydroxy, or
PNG
media_image1.png
2
9
media_image1.png
Greyscale
PNG
media_image1.png
2
9
media_image1.png
Greyscale
PNG
media_image1.png
2
9
media_image1.png
Greyscale
(of Formula (I))
R2 is hydrogen, chloride
R3 is fluoride
Ra is hydrogen
n is 0
Rb is not exemplified
R5 is —(C1alkyl)-R6 or —(C1alkyl)NRcRd wherein Rc and Rd, together with the nitrogen atom to which they are attached, form a five to ten-membered ring monocyclic or bicyclic ring optionally containing one additional heteroatom selected from nitrogen and oxygen, and sulfur, wherein the ring is optionally substituted with one or two groups independently selected from C1alkoxy, C1alkyl, Fluoro; or one of Rc and Rd is selected from C1alkyl and the other is C1alkyl, and wherein R5 is
PNG
media_image2.png
83
51
media_image2.png
Greyscale
R6 is selected from: a C3cycloalkyl substituted with NRcRd(C1-C3alkyl); and a five- to ten-membered monocyclic orbicyclic containing one nitrogen atom and optionally a second heteroatom selected from oxygen or nitrogen, wherein the ring contains zero double bonds and wherein the ring is optionally substituted will will
Therefore, the compounds and methods described in the instant specification detail only a limited number of the total substituents claimed (see substituents 1-8, above). All working examples presented in the instant specification are related to the compounds containing a fraction of the total claimed substituents (see substituents 17-24, above).
There are no working examples in the instant specification for the wide range of substituents claimed, but for which evidence of possession has not been provided (see substituents 9-16, above). Thus the instant specification does not provide any evidence that Applicant was in possession of the claimed invention prior to the effective filing of the instant application.
Vas-Cath Inc. Mahurkar, 19 USPQ2d 1111, makes clear the "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116).
Finally, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 held that: ...To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F. 3d 1565, 1572, 41 USPQ2d 1961, 1966(1997); In re Gosteli, 872 F.2d 1008, 1012,10 USPQ2d 1614, 1618 (Fed Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.") Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.
It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. For inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession. For example, disclosure of only a method of making the invention and the function may not be sufficient to support a product claim other than a product-by-process claim. See, e.g., Fiers v. Revel, 984 F.2d at 1169, 25 USPQ2d at 1605; Amgen, 927 F.2d at 1206, 18 USPQ2d at 1021.
Thus, since Applicant has not described in adequate detail methods to synthesize compounds containing the claimed substituents, or provided evidence that said compounds have been characterized, or that they exist, an ordinary skilled artisan could not completely envisage Applicants’ invention. Moreover, it is clear that the written description requirement has not been met since Applicant has not provided any evidence that Applicant was in possession of the claimed invention prior to the effective filing of the instant application. Thus, claims 1-5, 7, 8, 11, 15-17, 20, 21-22, and 25-28 of the instant application are not supported by the instant specification and thus a rejection under 35 U.S.C. § 112 (a) for failing to comply with the written description requirement is proper.
Claim Rejections - 35 U.S.C. § 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)(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.
Claims 1-5, 15, 17, 22, 23, and 25-28 are rejected under 35 U.S.C. § 102(a)(2) as being anticipated by Zhang et al. (WO 2022061251 A1, effectively filed January 21, 2021 for the purpose of 35 U.S.C. § 102 (a)(2)), hereinafter Zhang.
The instant claims are drawn to a compound of Formula (I), a method for treating cancer susceptible to KRAS G12D inhibition, including pancreatic cancer, colorectal cancer, and lung cancer, comprising the administration of a pharmaceutical composition comprising a compound of Formula (I).
Zhang teaches compounds and methods for KRAS modulation (Title). Specifically, Zhang teaches compound P-0046 (claim 1, embodied as Example 2, pages 161 and 162, paragraph [0359-0361]), also known as CAS Registry Number: RN 2765344-69-0. [Database Registry Chemical Abstracts Service, Columbus, Ohio, Accession No. RN 2765344-69-0. Entered STN: 14 Apr 2022], as shown in Figure 1, below. Zhang anticipates the instant claims wherein,
R1 is aryl (naphthyl) substituted with hydroxide,
PNG
media_image3.png
141
128
media_image3.png
Greyscale
(see instant claims 1, 15, 17, 22, and 23)
R2 is Chloro (see instant claims 1, 3, 22, and 23)
R2 is Fluoro (see instant claims 1, 3, 22, and 23)
R4 is
PNG
media_image4.png
144
72
media_image4.png
Greyscale
, wherein Ra is H (see instant claims 1, 2, 22, and 23)
R5 is –(C1 alkyl)—R6, wherein R6 is a five-membered monocyclic ring containing one nitrogen atom, i.e. R5 is
PNG
media_image5.png
82
89
media_image5.png
Greyscale
(see instant claims 1, 4, 5, 22, and 23)
Figure 1. Structural comparison of prior art compound and instantly claimed Formula (I)
PNG
media_image6.png
367
827
media_image6.png
Greyscale
Figure 1. a) Zhang CAS Registry Number: RN 2765344-69-0; b) instantly claimed Formula (I)
Regarding claim 23, compound P-0046 anticipates the compound claimed on page 11, line 1 of the instant claim exemplified as
PNG
media_image7.png
154
204
media_image7.png
Greyscale
.
Regarding claim 25, teaches a pharmaceutical composition comprising the instantly claimed compound (claim 26).
Regarding claim 26, Zhang teaches a method for treating a disease mediated by KRAS (claim 28) comprising the administration of the instantly claimed compound, and specifically teaches that the compounds of the disclosure inhibit KRAS G12D (paragraph [0012]).
Regarding claims 27 and 28, embodiment 30 of Zhang teaches wherein the compounds of the prior art are used to treat pancreatic cancer, colorectal cancer and lung cancer (paragraph [0294]) and the disclosure teaches wherein the G12D mutation of KRAS has been implicated in said cancers (paragraph [0008]).
Within the disclosure of Zhang, numerous compounds anticipate the compounds of the instant claims (see Table 1A pages 195-388).
Correspondence
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sophia P. Hirakis whose telephone number is +1 (571) 272-0118. The examiner can normally be reached within the hours of 5:00 am to 5:00pm EST, Monday through Friday.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C. Milligan can be reached on +1 (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is +1 (571) 273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call +1 (800) 786-9199 (IN USA OR CANADA) or +1 (571) 272-1000.
/SOPHIA P HIRAKIS/Examiner, Art Unit 1623
/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623