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, 2, 9, 12, 16, 18, 20, 22, 25, 27, 30, 32, 36, 38, 53, 79, 88, 90, 91, and 94 are pending. Claims 3-8, 10, 11, 13-15, 17, 19, 21, 23, 24, 26, 28, 29, 31, 33-35, 37, 39-52, 54-78, 80-87, 89, 92, 93, and 95 are cancelled.
Status of Priority
The present application is a 35 U.S.C. § 371 national stage patent application of International patent application PCT/US2022/079896, filed on November 15, 2022. This application also claims the benefits of priority to U.S. Provisional Application No. 63/279,353, filed on November 15, 2021; 63/338,210, filed on May 4, 2022; 63/374,491, filed on September 2, 2022; 63/383,113, filed on November 10, 2022.
Specification - Abstract
Applicant is reminded of the proper content of an abstract of the disclosure.
In chemical patent abstracts for compounds or compositions, the general nature of the compound or composition should be given as well as its use, e.g., “The compounds are of the class of alkyl benzene sulfonyl ureas, useful as oral anti-diabetics.” Exemplification of a species could be illustrative of members of the class.
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 is not in compliance with 37 C.F.R. 1.72 (b). Specifically, the sheet presenting the abstract includes other parts of the application or other material. 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).
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 Rejections - 35 USC § 112(a)
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.
Scope of Enablement
Claims 1, 2, 9, 12, 16, 18, 20, 22, 25, 27, 30, 32, 36, 38, 53, 79, 88, and 91 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
A compound of Formula (I), or pharmaceutically acceptable salt thereof:
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wherein
R1 is H;
R2 is halogen, C1-C3 alkyl, C1-C3 haloalkyl, -C(=O)NH2, or C3-C6 cycloalkyl;
R3 is H;
W, X, and V are as recited in instant claim 1;
Y, Z, and Y-Z are as recited in instant claim 1;
wherein
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is a 5- to 8-membered ring;
R4 is as recited in instant claim 1;
R5 is H, C1-6 alkyl, C1-6alkyl-OCH3, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkyl-C3-6cycloalkyl, or
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;
R6 = H or C1-6 alkyl;
Ring A is selected from the group consisting of:
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,
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,
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,
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,
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, phenyl, pyridinyl, and pyrazolyl;
Each R7 is independently halogen, C1-6 haloalkyl, C1-6 alkyl, C3-6 cycloalkyl, -S-(C1-6 alkyl), or 4-8 membered heterocycloalkyl containing 1-2 N and/or O atoms
Each R7a is independently OH, CN, C1-6 alkyl, C3-6 cycloalkyl, -C(=O)NH2, -C(=O)NH(C1-3 alkyl), -N(C1-3 alkyl)2,
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, or -O-C1-6 haloalkyl
n = 0-3
R = C1-6 alkyl, C3-6 cycloalkyl, OH, or
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;
A compound of Formula (II), or pharmaceutically acceptable salt thereof:
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R1, R2, Ring A, R7, and n are as defined above in points 1a, 1b, 1j, 1k, and 1m, respectively;
R3 = H or C1-6 alkyl;
R8 = -C(=O)NH2, -C(=O)NH(C1-3 alkyl), -C(=O)N(C1-3 alkyl)2,
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, -NH2, CN, -NH-S(=O)2-(C1-3 alkyl), -S(=O)2NH2, -S(=O)2-(C1-3 alkyl), -P(=O)(C1-3 alkyl)2, -S(=O)2(C1-3 alkyl)-OCH3, or -S(=O)2(C1-3 alkyl)-(6-membered heterocycloalkyl);
R9 = H, C1-6 alkyl, -(C1-6 alkyl)-OCH3, -O-(C1-6 alkyl)-OCH3, -C(=O)NRcRd wherein Rc and Rd are taken together with the atom to which they are attached to form a 6-membered heterocycloalkyl, -C(=O)NH2, -(C1-6 alkyl)-(6-membered heterocycloalkyl), or 6-membered heterocycloalkyl
does not reasonably provide enablement for elements that are outside the scope of the enabling elements listed above. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
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 to make and use the invention based on the content of the disclosure, 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 compounds that are ULK1/2 inhibitors and their use in the treatment of disorders such as cancers.
State of the prior art and the predictability or lack thereof in the art
The prior art discloses compounds encompassed by the scope of the instant claims. However, these previously disclosed compounds have been reported in the prior art as ERK inhibitors, CDK inhibitors, or general kinase inhibitors rather than ULK1/2 inhibitors. Thus, the prior art does not provide a predictable structure-activity relationship from which a POSITA could reasonably determine which combinations of substituents, substitution patterns, or substitution positions would result in compounds having ULK1/2 inhibitory activity. Accordingly, the prior art demonstrates that kinase target selectivity within the claimed genus is unpredictable.
See “Claim Rejections - 35 USC § 102” section below for details.
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 medicinal chemistry and organic synthesis and would be familiar with standard methods for evaluating therapeutic efficacy of compounds.
The breadth of the claims
The claims are broad insofar as the instant claims recite a compound of general formula (I) and (II) wherein the compound can possess a structurally diverse range of chemical groups.
The presence or absence of working examples
The instant specification provides 409 specific examples of compounds encompassed by instant formulas (I) or (II). Despite the relatively larger number of exemplified compounds, the working examples still do not adequately represent the full breadth of the claimed genus. For example, with respect to Formula (I), R1 is consistently hydrogen throughout the working examples and the exemplified values of “n” do not exceed 3. Furthermore, the instant claims allow Ring A to be any aryl or any heteroaryl, however, the working examples only give a few specific examples of what these aryl or heteroaryls can be. Accordingly, significant portions of the claimed structural space remain unexplored by the working examples. The examples, therefore, provide only limited information regarding how variations in substituent identity, substituent number, and substituent position affect ULK1 inhibitory activity across the full scope of the claimed genus.
The amount of direction or guidance present and the quantity of experimentation needed to make and use the invention based on the content of the disclosure
Although the specification provides synthetic procedures for the specific examples encompassed by the instant claims, it provides limited direction and guidance regarding which structural features are responsible for ULK1/2 inhibitory activity and how modifications to the claimed variables affect such activity. For example, formula (I) permits Ring A to contain from 0 to 7 R7 substituents selected from a broad list of chemical groups recited in instant claim 1. However, the working examples contain compounds having no more than three R7 substituents on ring A. The specification does not provide guidance regarding the effect of increasing substitution on Ring A to seven substituents, nor does it provide a structure-activity relationship that would allow a POSITA to predict whether compounds having three, four, five, six, or seven R7 substituents would retain ULK1/2 inhibitory activity.
Likewise, the specification does not provide guidance regarding how changes in the identity, position, and combination of substituents affect ULK1/2 inhibitory activity. Variations in substituent number and placement can substantially alter steric properties, conformational preferences, electronic distribution, intermolecular interactions, and protein-binding characteristics. The specification does not identify which of these features are important for achieving the claimed activity, nor does it provide predictive principles by which a POSITA could distinguish operative compounds from inoperative compounds across the breadth of the claims.
Because the claims encompass numerous variables, each having multiple permissible values, the required experimentation would involve not merely routine verification of activity but extensive exploration of the claimed genus to identify operative species which involves undue experimentation. Although a POSITA possesses expertise in medicinal chemistry and organic synthesis, such expertise cannot substitute for the absence of guidance in the specification. The issue is not whether a POSITA is capable of synthesizing and testing compounds encompassed by the claims. Rather, the issue is that the specification provides insufficient information to identify which structural modifications (e.g., which combinations of substituents, substitution patterns, and number of substitution) preserve ULK1/2 inhibitory activity and which modifications destroy such activity. Consequently, a POSITA would be required to undertake a substantial medicinal chemistry research program to establish the relevant structure-activity relationships before the full scope of the claimed genus could be practiced.
Claims 2, 9, 12, 16, 18, 20, 22, 25, 27, 30, 32, 36, 53, 79, 88, and 91, which are dependent on claim 1, are also rejected for further requiring and/or reciting elements that are outside the scope of the enabling elements listed above.
Enablement
Claim 94 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 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 to make and use the invention based on the content of the disclosure, 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 compounds that are ULK1/2 inhibitors and their use in the treatment of disorders such as cancers.
State of the prior art and the predictability or lack thereof in the art
Prior art referenced:
Mao et al. (Mao) (Mao, L. et al. ULK1 phosphorylates Exo70 to suppress breast
cancer metastasis. Nature Communications 2020, 11, 117.)
Mao teaches that “Over expression of ULK1… significantly inhibited migration and invasion of the metastatic MDA-MB-231 cells without affecting their growth or survival during the observed period… Reversely, knocking down ULK1 in the low metastatic cell line MCF-7 increased its invasion and migration ability as indicated by the transwell assay and wound healing assay” (Pg. 2, right col., 1st paragraph).
From the teachings of Mao, a POSITA would understand that reduced ULK1 activity can promote invasive and migratory behavior in at least certain breast cancer cell lines, but not in others. Accordingly, Mao demonstrates that inhibition of ULK1 is not uniformly associated with a therapeutic benefit in all cancer contexts and that the biological outcomes of ULK1 inhibition are dependent upon the particular cancer type. Furthermore, a POSITA would not have been able to reliably predict the therapeutic effect of ULK1 inhibition across different cancer types.
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 medicinal chemistry and organic synthesis and would be familiar with standard methods for evaluating therapeutic efficacy of compounds.
The breadth of the claims
The claims are broad insofar as the instant claims recite a method of treating any cancer comprising administering to a subject a compound of general formula (I) or pharmaceutically acceptable salt thereof wherein the compound can possess a structurally diverse range of chemical groups.
The presence or absence of working examples
The instant specification only provides data showing inhibition of ULK1 in a biochemical assay by the exemplified compounds. The instant specification does not provide evidence demonstrating that the instant compounds exhibit anticancer activity in vitro in cancer cell lines or in vivo in xenograft or other animal models. As a result, the specification does not demonstrate that inhibition of ULK1 activity necessarily translates into efficacy for the treatment of all cancer (note: instant claim 94 recites “treating cancer” which encompasses all cancers).
The amount of direction or guidance present and the quantity of experimentation needed to make and use the invention based on the content of the disclosure
The specification provides limited guidance regarding the use of the claimed compounds for the treatment of all cancer. In particular, the specification provides only biochemical assay data demonstrating inhibition of ULK1 activity by the exemplified compounds. The specification does not provide data demonstrating anticancer activity in cancer cell lines, inhibition of tumor growth in animal models, efficacy in any particular cancer type, or guidance regarding which cancers, if any, are susceptible to treatment through ULK1 inhibition by the instant compounds.
The absence of such guidance is particularly significant in view of the unpredictability of the prior art. As discussed above, Mao teaches that reduction of ULK1 activity can increase invasion and migration in certain breast cancer cells, thereby demonstrating that inhibition of ULK1 is not uniformly associated with a therapeutic benefit and that the biological outcomes of ULK1 inhibition are dependent upon the particular cancer type. Thus, a POSITA would not reasonably expect that inhibition of ULK1 necessarily results in treatment of all cancer.
Accordingly, a POSITA seeking to practice the full scope of the claimed method would not merely be required to confirm the efficacy of the disclosed compounds. Rather, the POSITA would first need to determine which cancer types are responsive to ULK1 inhibition, whether ULK1 inhibition produces a therapeutic benefit or a detrimental effect in a given cancer type, and whether the disclosed compounds possess sufficient cellular and in vivo activity to achieve the claimed therapeutic result. Such determinations would require extensive biological investigation involving the selection and evaluation of numerous cancer cell lines, animal models, and disease contexts. Because the specification provides little guidance for making these determinations and because the prior art teaches that the biological outcomes of ULK1 inhibition are cancer dependent and unpredictable, the quantity of experimentation required to practice the full scope of the claimed method would be undue.
Written Description
Claims 1, 2, 9, 12, 16, 18, 20, 22, 25, 27, 30, 32, 36, 38, 53, 79, 88, 91, and 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 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.
In the instant case, the claims are exceedingly broad. In particular, the instant claims recite a compound of general formula (I) and (II) wherein the compound can possess a structurally diverse range of chemical groups. The instant claims also recite a method of treating any cancer comprising administering to a subject a compound of general formula (I) wherein the compound can possess a structurally diverse range of chemical groups.
The instant specification provides 409 specific examples of compounds encompassed by instant formulas (I) or (II). Despite the relatively larger number of exemplified compounds, the working examples still do not adequately represent the full breadth of the claimed genus. For example, with respect to Formula (I), R1 is consistently hydrogen throughout the working examples and the exemplified values of “n” do not exceed 3. Furthermore, the instant claims allow Ring A to be any aryl or any heteroaryl, however, the working examples only give a few specific examples of what these aryl or heteroaryls can be. Accordingly, significant portions of the claimed structural space remain unexplored by the working examples. The examples, therefore, provide only limited information regarding how variations in substituent identity, substituent number, and substituent position affect ULK1 inhibitory activity across the full scope of the claimed genus
Furthermore, the instant specification only provides data showing inhibition of ULK1 in a biochemical assay by the exemplified compounds. The instant specification does not provide evidence demonstrating that the instant compounds exhibit anticancer activity in vitro in cancer cell lines or in vivo in xenograft or other animal models. As a result, the specification does not demonstrate that inhibition of ULK1 activity necessarily translates into efficacy for the treatment of all cancer (note: instant claim 94 recites “treating cancer” which encompasses all cancers.
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).
Therefore, the instant specification does not adequately reflect the structural diversity of the claimed genus and does not demonstrate possession of the full scope of compounds encompassed by the instant claims.
Additionally, the prior art demonstrates that inhibition of ULK1 is not uniformly associated with a therapeutic benefit in all cancer contexts (see “Enablement” section – “2. State of the prior art and the predictability or lack thereof in the art” subsection for details). Therefore, the instant specification does not reasonably convey to a POSITA that the Applicants were in possession of a method of treating the full scope of cancers encompassed by the instant claims.
In summary, the instant specification discloses only a limited subset of the compound species encompassed by the claimed genus and fails to provide representative species to demonstrate possession of the full breadth of the claimed compounds. Moreover, while the specification demonstrates ULK1 inhibitory activity in a biochemical assay, it does not demonstrate that the claimed compounds provide a therapeutic benefit in all cancer models. Therefore, the specification does not reasonably convey to a POSITA that the Applicants were in possession of both the full scope of the claimed compound genus and the broadly claimed method of treating any cancer.
Claims 2, 9, 12, 16, 18, 20, 22, 25, 27, 30, 32, 36, 53, 79, 88, 91, and 94, which are dependent on claim 1, are also rejected for further requiring and/or reciting elements that do not have written description support.
The instant application only has written description support for the compounds encompassed by points 1a-1n and 2a-2d as explicitly recited in the “Scope of Enablement” section above.
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 90 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 90 recites 409 compounds that are claimed to be compounds of claim 1. However, claim 1 requires the thiophene ring to be fused to
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is a 5- to 8-membered ring (see 1st line of pg. 4 of the amended claim set). Yet, in claim 90, it recites compounds wherein the thiophene is not fused with a 5- to 8-membered ring (see compounds 1-3, 5-20, 25-27, 32, 37, 38, 45, 51, 52, 54-59, 61-63, 65-68, 72, 73, 75-81, 83, 87-108, 110-115, 118-124, 127-133, 136, 137, 145, 404, and 405). Therefore, claim 90 is in improper dependent form for failing to further limit the subject matter of the claim upon which it depends and, instead, broadens the scope of 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.
Note on 35 USC § 102 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.
Claims 1, 2, 12, 16, 18, 20, 22, 27, 30, 36, 38, 53, 79, 91, and 94 are rejected for being anticipated by the prior art as discussed below.
Rejection Part 1:
Claims 1, 2, 12, 16, 18, 20, 36, and 79 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
Cortez et al. (Cortez) (US 2016/0176896 A1; published June 23, 2016)
Cortez discloses ERK inhibitors which includes the following compound:
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(see pg. 24 of Cortez, compound 19; herein, this compound will be referred to as compound-19-Cortez).
Compound-19-Cortez is encompassed by the instant claims wherein:
R1 = R2 = R3 = H
W = -C(=O)-
V is null
Z = NR5
R5 = C2 alkyl substituted with R
R = heterocycloalkyl (i.e., morpholinyl)
X is null
Y = -C(R6)2-
R6 = C1 alkyl (i.e., Me)
Ring A = aryl (i.e., phenyl)
R7 = halogen (i.e., F)
n = 2
OR wherein:
R1 = R2 = R3 = H
W = -C(=O)-
V and Z is null
Y = NR5
R5 = C2 alkyl substituted with R
R = heterocycloalkyl (i.e., morpholinyl)
X = -C(R6)2-
R6 = C1 alkyl (i.e., Me)
Ring A = aryl (i.e., phenyl)
R7 = halogen (i.e., F)
n = 2
Therefore, compound-19-Cortez anticipates instant claims 1, 2, 12, 16, 18, 20, 36, and 79.
Rejection Part 2:
Claim 53 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
Cortez et al. (Cortez) (US 2016/0176896 A1; published June 23, 2016)
Cortez discloses ERK inhibitors which includes the following compound:
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(see pg. 21 of Cortez, compound 6; herein, this compound will be referred to as compound-6-Cortez).
Compound-6-Cortez is encompassed by the instant claims wherein:
R1 = R3 = H
R2 = CF3
W = -C(=O)-
V is null
Z = NR5
R5 = C2 alkyl substituted with R
R = heterocycloalkyl (i.e., morpholinyl)
Y is null
X = -C(R6)2-
R6 = C1 alkyl (i.e., Me)
Ring A = heteroaryl (i.e., pyrazolyl)
R7 = C1 alkyl (i.e., Me)
n = 1
Therefore, compound-6-Cortez anticipates instant claim 53.
Rejection Part 3:
Claims 22, 27, and 30 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by:
Buesking et al. (Buesking) (US 2022/0089608 A1; published March 24, 2022; Filed September 21, 2021; Effective filing date: September 21, 2020)
Buesking discloses CDK inhibitors which includes the following compound:
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(see example 56, para. 0910 of Buesking; herein, this compound will be referred to as compound-56-Buesking).
Compound-56-Buesking is encompassed by the instant claims wherein:
R1 = H
R2 = halogen (i.e., F)
R3 = C1 alkyl (i.e., Me)
W = -C(=O)NR4
R4 = H
V is null
Y-Z = -CR6=CR6-
One R6 is H and the other is C3 alkyl (i.e., isopropyl)
X is null
Ring A = heteroaryl (i.e., pyridinyl)
R7 = heterocycloalkyl (i.e., piperidinyl) substituted with R7a
R7a = C1 alkyl (i.e., Me)
n = 1
Therefore, compound-56-Buesking anticipates instant claims 22, 27, and 30.
Rejection Part 4:
Claims 91 and 94 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
Bhagwat et al. (Bhagwat) (Bhagwat, S. V. et al. ERK Inhibitor LY3214996 Targets ERK Pathway–Driven Cancers: A Therapeutic Approach Toward Precision Medicine. Mol Cancer Ther 2020, 19, 325-336.)
Bhagwat discloses the following ERK inhibitor:
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(see pg. 327, Figure 1A; herein, this compound will be referred to as LY3214996).
LY3214996 is encompassed by the instant claims wherein:
R1 = R2 = R3 = H
W = -C(=O)-
V is null
Z = NR5
R5 = C2 alkyl substituted with R
R = heterocycloalkyl (i.e., morpholinyl)
Y is null
X = -C(R6)2-
R6 = C1 alkyl (i.e., Me)
Ring A = heteroaryl (i.e., pyrazolyl)
R7 = C1 alkyl (i.e., Me)
n = 1
Bhagwat further discloses that “LY3214996 demonstrates potent in vivo antitumor activity in BRAF-, KRAS-, NRAS-, and MEK-mutant models as a single agent” (see pg. 332, left col., middle section; anticipates instant claim 94).
In the in vivo xenograft studies, the nude mice that were injected with the tumor cells were administered a pharmaceutical composition comprising LY3214996 in hydroxyethylcellulose 1% (w/v)/P80 0.25% (v/v)/antifoam 1510-US 0.05% (v/v) (see pg. 326, right col., “In vivo studies” section, 2nd paragraph, 1st sentence). In other words, Bhagwat teaches a pharmaceutical composition comprising a compound of instant claim 1 and a pharmaceutically acceptable excipient and, therefore, anticipates instant claim 91.
Therefore, Arnold-compound anticipates instant claims 91 and 94.
Conclusion
No claims are allowed. 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
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