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 1-20 are pending.
Election/Restrictions
Claim 20 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on August 12, 2026.
Applicant’s election of the species compound of formula I:
the Species of Compound 1 of Application Example 1,
PNG
media_image1.png
144
420
media_image1.png
Greyscale
and
(B) cancer in the reply filed on August 12, 2026, is acknowledged.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
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 September 18, 2025, is 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: per MPEP 608.01 and 37 CFR 1.52 (b)(2)(i), the specification must have lines 1 ½ or double spaced. The current specification is single spaced. Appropriate correction is required.
While not required by the MPEP, it is suggested to number the specification with line numbers or alternatively number the paragraphs.
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 9 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 9 depends from claim 1 and recites R4 is “=O.” There is no antecedent basis for this in claim 1, where R4 is defined as follows.
PNG
media_image2.png
156
732
media_image2.png
Greyscale
Applicant may cancel claim 9, amend the claim to place it 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 § 112 (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.
Claims 1-11 and 14-19 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’, stereoisomer or a pharmaceutically acceptable salt thereof,
PNG
media_image3.png
180
316
media_image3.png
Greyscale
PNG
media_image4.png
472
736
media_image4.png
Greyscale
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. Claims 12-13 recite the claimed and elected species and other individual species. Claims 12-13 are 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 10-12 compounds of claims 12-13 and also found in the specification.
In contrast to the broad claimed scope of ring A, R1, R2, R3, R4, R4, R5, R6, of the claims, the supporting disclosure (claims 12-13 and the specification) are limited to the following:
Ring A is limited to phenyl, pyrazolyl, and pyridinyl;
R1 is limited to hydrogen, methyl and CF2H;
R2 is limited to methyl, Cl, C(O)NH2; CH2OH;
R3 is limited to hydrogen
R4, R5 and R6 are limited to hydrogen, methyl, chloro, fluoro, CF3, NH2, NHCH3, NHOCH3, and CF2H; and
of the spiro portion of formula I’, the NH2 is attached only in one as follows:
PNG
media_image5.png
86
112
media_image5.png
Greyscale
Applicant’s disclosure of the 10-12 compounds of claims 12-13 and detailed in the specification, is not a sufficient representation of all the claimed compounds of claim 1 and its dependent claims.
Other than the working examples of the specification (starting with Example 1, compound 1 at page 16 and claims 12-13), 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 Applicant has not 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. 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 (Enablement)
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 15-17 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 15-17 are directed to methods of preventing or treating a broad scope of diseases and conditions with the SHP2 inhibitors of claim 1. The specification does not enable any person having ordinary skill 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 difficulty in treating or preventing SHP2 diseases as claimed.
With regard to just elected species 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.
In fact, with a particular species, pancreatic cancer, Halbrook et al.4 teaches, despite significant progress that has been made in understanding the biology of pancreatic cancer, “unfortunately, these have not translated into a breakthrough in clinical care for the majority of patients.“ See Section Conclusions, p. 1743, column 1.
Despite the advances in PDAC (pancreatic ductal adenocarcinoma) treatment, Halbrook details the difficulty in treating pancreatic cancer as detailed below.
Halbrook notes even with surgical resection of pancreatic cancer, nearly 3 in 4 patients will develop recurrence of pancreatic cancer within 2 years, as the patients harbor micro-metastatic pancreatic cancer disease. See page 1730, column 1.
Halbrook notes even the state of the art therapy of chemoradiation in conjunction with adjuvant chemotherapy, patients survival rates remain in 5-year overall survival (OS) compared with patients with upfront surgery with adjuvant therapy (20.5% vs. 6.5%). See page 1730, column 1.
Halbrook teaches how the pancreatic tumor microenvironment (TME) provides particular challenges with treating pancreatic cancer. See page 1734, column 2.
The pancreatic TME is composed of numerous [noncancerous] populations of fibroblasts, dense extracellular matrix, a poorly formed vascular system, and a diverse and largely suppressive populations of immune cells. The neoplastic cells in PDAC often constitute a minority of the overall cellularity within the tumor. Indeed, the aggressive biology, resistance to therapy, and heterogeneity of the disease is driven nearly as much by the non-cancerous components of the tumor as the PDAC cells. See page 1734, column 2.
Note, the only current approach to the prevention aspect of cancer are vaccines as per Halbrook. See page 1743, column 1. The small molecules SHP2 modulating compounds of the invention are NOT vaccines.
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 prevention or treatment of any SHP2 mediated disease/ disorder/condition, including the treatment and prevention of the broad elected species, cancer. The broad scope is a Wands factors weighing against enablement of the rejected claims.
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 in Applicant’s specification, either in vivo or in vitro to enable the prevention or treatment of any diseases or conditions, let alone the treatment of any SHP2 modulated cancer. At best, Experimental Examples 2-5 note in vitro and in vivo lab models of 10-12 compounds exemplified by claims 12-13 and the specification.
The lack of working examples is a Wands factor against the enablement of the claimed invention.
In summary, per the Wands factors detailed above, the claims are not enabled for the full scope as claimed.
Conclusion and Correspondence
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/CN2022/127937 10/27/2022
FOREIGN APPLICATIONS
CHINA 202111257617.8 10/27/2021
CHINA 202111402382.7 11/19/2021
CHINA 202210045128.4 01/14/2022
CHINA 202211275680.9 10/18/2022
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
4 Halbrook et al. Pancreatic cancer: Advances and challenges Cell Volume 186, Issue 8p1729-1754April 13, 2023
Prosecution Insights