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 .1
Status of Claims
Claims 1-10 are pending.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-8 in the reply filed on 4/20/2026 is acknowledged.
Applicant elected, without traverse, (3S ,4S)-8-( 6-amino-5-(3-chloro-2-(( 1 -methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-ylthio)pyrazin-2-yl)-3-methyl-2-oxa-8-azaspiro[4.5]decan-4-amine (compound of Example 4, ZB-S-85 and claim 7).
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Claims 9-10 were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected Group/Invention II, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 4/20/2026.
It is noted upon further search and consideration, the restriction requirement between groups I and II is withdrawn, and claims 9-10 are rejoined.
The species election requirement remains in place.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on March 27 2026 and Nov 13 2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The disclosure is objected to because of the following informalities:
The specification is objected to for multiple instances of reciting formulas I and Ia.
Both formula I and Ia recite “p” and “q” in their chemical structures but the font size for both variables is so small they are near illegible, see formula I at page 2, lines 7-9, reproduced below for example.
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Appropriate correction is required.
Claim Objections
Claims 1, 2 and 7 are objected to because of the following informalities:
Claims 1 and 2 are objected to for lack of clarity with regard to formulas I and Ia. Both formula I and Ia recite “p” and “q” in their chemical structures but the font size for both variables is so small they are near illegible, see formula I below for example.
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Appropriate correction to enlarge the font for p and q will overcome this objection.
Claim 1 recites the typo “finve” in line 11 of the claim, between the terms “one to” and “substituents. . . .” It is clear it is supposed to be “five.”
Claim 7 is objected to as it requires the term “and” to between its last two compounds ZB-S-106 and ZB-S-107, see below.
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Appropriate correction is required.
Claim 7 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Interpretation
Note where claim 1 recites X is absent, the absence of X in a species is interpreted as X being a bond between the two moieties it is attached to.
Claim Rejections - 35 USC § 112
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 1-5 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.
Claims 1-5 recite “3- to 10-membered heterocycloalkyl” in a list of moieties for R2, which can be further optionally substituted. However, the claims do not provide antecedent basis for “3- to 10-membered heterocycloalkyl,” but rather recite the previous basis, “3- to 10-membered heterocyclyl.” Amendment of the claims to recite “heterocyclyl” rather than “heterocycloalkyl” will overcome this rejection.
Claim Rejections - 35 USC § 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 1-6 and 8-10 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 claims contain 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.
The Claimed Invention
The claimed invention (claim 1) is directed to a compound of formula I, as detailed above, where R1, R2, R3, R4a, R4b, R5a, R5b, R6a, R6b, R7a, R7b, R8, R9, X, Y, Z1, Z2 and Z3 are broadly claimed as recited therein.
Certain narrower embodiments of the claimed invention are presented in various dependent claims. Some of these claims further limit the claimed groups and substituents as detailed therein. Claim 7 recites the claimed and elected species and other individual species. Claim 7 is NOT rejected for written description.
The Supporting Disclosure
Applicants’ supporting disclosure contains certain descriptions and embodiments of the claimed invention.
In the present case, the important factors leading to a conclusion of inadequate written description is the absence of sufficient working examples of the invention as claimed, and the lack of predictability in the art.
In the present case there is no disclosure of compounds having the broad and full scope definitions of the groups and substituents of claim 1. In fact, the scope of compounds that provide adequate written description are the 26 compounds of claim 7 and also found on pages 9-10 of the specification.
In contrast to the broad claimed scope of R1, R2, R3, R4a, R4b, R5a, R5b, R6a, R6b, R7a, R7b, R8, R9, X, Y, Z1, Z2 and Z3 of the claims, the supporting disclosure (claim 7, pages 9-10 and associated experimental examples starting at page 11), are limited to the following:
R1 is limited to NH2;
R2 is limited to nitrogen containing heteroaryl, cycloalkyl and heterocyclyl containing oxygen and nitrogen;
R3 is limited to halogen (chloro);
X is always present and is always sulfur:
Z1 is limited to N or -CH;
Z2 and Z3 are limited to -CH;
Y is limited to -CH;
R4a, R4b, R5a, R5b, R6a, R6b, R7a, R7b are limited to hydrogen;
R8 and R9 are limited to be combined and form along with the piperidine they are attached to a spiro group (i.e., the moiety V of claim 5), where V is
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(oxa-8-azaspiro[4.5]decan-4-amine).
Applicant’s disclosure of the 26 compounds of claim 7, is not a sufficient representation of all the claimed compounds of claim 1 (and rejected dependent claims) as presently pending.
Other than the working examples of the specification (26 compounds of pages 9-10 and working examples starting at page 11), Applicant has not reasonably described a scientific or “systematic” approach to synthesize the full scope of claim 1 and claims dependent. See MPEP 2163.02, the standard for determining compliance with the written description.2
Although Applicant has written description support for the 26 compounds of pages 9-10 and also found in claim 7, Applicant has not provided reasonably provided a description the support the broader scope of the claimed compounds of formula I.
Accordingly, Applicants have not adequately described the invention for the breadth that is claimed. It thus appears that Applicants were not in possession of the claimed invention at the time the application was filed, the full scope of compounds of formula I, and that Applicants’ species do not support the claimed genus.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(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 9-10 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.
Claims 9-10 are directed to methods of treating a broad scope of diseases and conditions with the claim 1 SHP2 inhibitors. The specification does not enable any person having ordinary skilled in the art (PHOSITA) to which it pertains, or with which it is most nearly connected, to practice the invention.
Applicant’s attention is drawn to In re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set eight forth factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors: (1) the nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
The predictability or unpredictability of the art: The instant claimed invention is highly unpredictable since a person having ordinary skill in the art (PHOSITA) recognizes the unpredictability in SHP2 inhibition to treat ANY SHP2 modulated disease of claims 9-10, let alone a single disease/disorder including the broad category of cancer.
With regard to just cancer alone, Song et al.3 notes while SHP2 is a promising therapeutic target for cancer therapy (see abstract), it notes “the inherent drawbacks of PTP [i.e. SHP2] orthosteric inhibitors. . . [include] poor membrane permeability, low oral bioavailability, low potency, and possible off-target effects, have hampered their clinical development. “ See page 3076, column 1. (Note that Song teaches that SHP2 is encoded by PTPN11 dephosphorylase belonging to the protein tyrosine phosphatase (PTP) family). See Introduction page 3066, column 1.
Accordingly, the unpredictability in the art is Wands factor against enablement of the claims.
The breadth of the claims :The instant claims are deemed very broad since these claims read on treatment of any SHP2 mediated disease/disorder/condition of claim 9 or any cancer (and the myriad of unrelated non-cancer diseases) as claimed by claim 10. The broad scope is a Wands factors weighing against enablement of claims 9-10.
The amount of direction or guidance presented, and the presence or absence of working examples: It has been established that “the amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art.” In re Fisher, 427 F.2d 833, 839 166 USPQ 18, 24 (CCPA 1970).
It is pointed out that there is no working example, either in vivo or in vitro to enable the treatment of any diseases or conditions, let alone the treatment of any cancer, in Applicant’s specification. At best, starting at page 39 of the specification, Examples 27-29, Tables 1-2 provide biological assays (SHP2 inhibition, cell proliferation inhibition, IC50 data) of various compounds compared with a positive control (SHP099).
Therefore, in view of the Wands factors as discussed above, Applicant fails to provide information sufficient to practice the claimed invention as claimed.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-5 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over WO2018013597A1 (WO 597). WO 597 is cited on the IDS dated Nov 13 2023, For Ref 2.
Claims 1-5 are directed to compounds of formulas I, Ia Ib, Ic, and Id where X is S; R3 is a halogen (chloro); R1 is an alkyl (such as methyl or ethyl) or cycloalkyl (cyclopropyl); Y is carbon, Z2 is N; Z2 and Z3 are carbon; R4a, R4b, R5a, R5b, R6a, R6b, R7a,R7b are hydrogen and R8 and R9 are combined to form spiro compound (cyclopentyl) at the point of attachment, substituted with NH2.
Regarding claims 1-5, WO 597 discloses compounds 1, 2 and 3 below, which read on those above embodiments of claims 1 and 2, with regard to X, R1, R3, Z1,Z2, Z3, R4a-7a, R4b-7b, R8 and R9. See paragraph 161.
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It is noted compounds 1, 2 and 3 do not disclose the alkynyl functionality as per the claimed compounds. However, WO 597 teaches general formula I-A, which encompasses formulas 1, 2 and 3. See paragraph 76.
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General formula I-A encompasses species where the prior art’s R1 group is defined as a C2-C6 alkynyl group, that can be further substituted with various listed substituents. This teaching of an alkynyl of formula I-1 when combined with the teachings of compounds 1, 2 and 3, renders the claims obvious. See paragraph 7. Note that WO 597 teaches its compounds 1, 2 and 3, and the generic formula I-A that encompasses them, are known SHP2 inhibitors as the claimed compounds.
Prior to the filing of the instant application PHOSITA following the teachings of compounds 1, 2 and 3 and formula I-A, would have found it prima facie obvious to arrive at the claimed compounds. As formula I-A encompasses compounds 1, 2 and 3 and teaches variations where R1 is an alkynyl group as claimed, a PHOSITA would have predictably arrived at the claimed compounds which requires an alkynyl group. The rationale to do so is to combine the prior art teachings according to known methods to yield predictable results. See MPEP 2143(a).
Regarding claim 8, WO 507 teaches its SHP2 inhibitors (inclusive of Formula I-a) are formulated into pharmaceutical compositions comprising a pharmaceutically acceptable carrier and can further comprise an excipient, diluent or surfactant. See paragraph 18.
Conclusion and Correspondence
In summary, no claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM LEE whose telephone number is (571)270-3876. The examiner can normally be reached M-F.
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 at (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is 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 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/WILLIAM Y LEE/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
1 CONTINUING DATA
This application is a 371 of PCT/CN2022/084047 03/30/2022
FOREIGN APPLICATIONS
CHINA 202110523423.1 05/13/2021
Published as US 20240270753 A1
2 Whenever the issue arises, the fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, inventor was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991). An applicant shows that the inventor was in 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. Am. 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 inventor was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68,119 S.Ct. 304,312, 48 USPQ2d 1641, 1647 (1998); Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997); Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it"
3 Song et al. Strategies Targeting Protein Tyrosine Phosphatase SHP2 for Cancer Therapy J. Med. Chem. 2022, 65, 4, 3066–3079 https://doi.org/10.1021/acs.jmedchem.1c02008
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