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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06/27/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Nucleotide and/or Amino Acid Sequence Disclosures
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because it does not contain a "Sequence Listing" as a separate part of the disclosure or a CRF of the “Sequence Listing.”.
Required response - Applicant must provide:
A "Sequence Listing" part of the disclosure; together with
An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(a)(2);
A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 1.821(a)(4); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(a)(3).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
If the "Sequence Listing" part of the disclosure is submitted according to item 1) c) or d) above, applicant must also provide:
A CRF in accordance with 37 CFR 1.821(e)(1) or 1.821(e)(2) as required by 1.825(a)(5); and
A statement according to item 2) a) or b) above.
The Specification discloses a peptide on page 117.
For compliance with sequence rules, it is necessary to include the sequence in the “Sequence Listing” and identify them with SEQ ID NO. In general, any sequence that is disclosed and/or claimed as a string of particular bases or amino acids, and that otherwise meets the criteria of CFR 1.821(a), must be set forth in the “Sequence Listing.” See MPEP 2422.03.
While the Examiner has made every attempt to check the Specification for sequence compliance, Applicant is required to carefully check the entire Specification for any and all issues regarding sequence compliance.
For the response to this Office Action to be complete, Applicant is REQUIRED to comply with the Requirements for Patent Applications Containing Nucleotide Sequence And/ Or Amino Acid Sequence Disclosures. Failure to comply with the Requirements will be considered nonresponsive.
Specification
The disclosure is objected to because of the following informalities: In Table 2, pages 118-120, Examiner believes one of the table footnotes should have two stars “**” so as to match the first row of the table (see below).
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Appropriate correction is required.
Status of the Claims
Claims 1-44 and 53 are pending in this application. Claims 45-52 have been cancelled by applicant.
Claim Objections
Claims 1 and 38 are objected to because of the following informalities:
In claim 1, the definition of R2 (4th line from bottom of page 4 of claims) a space is missing in “C1-C3alkoxy” to read “C1-C3 alkoxy”.
In claim 38, most compounds listed have words that cut off at the end of the line (see examples below). Please amend to keep words together, and if splitting of terms is necessary, include a dash “-“ where the split should occur.
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Appropriate correction is required.
Examiner Notes
Claim 38 is free of the prior art, however, it stands objected over formal matters. Additionally, claim 38 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 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 41 and 53 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.
Claim 41 is indefinite because it reads as “a method of determining if a disease is associated with SHP2” after administration of the method of claim 40 has occurred. Furthermore, the term “determining” is not defined in the specification, thus, it is unclear what steps are comprised by this limitation. Furthermore, after some subjects are determined to have an SHP2-associated disease, those subjects will presumably receive treatment, however, it is unclear what will happen to subjects who are not determined to have an SHP2-associated disease (see 112(d) and 101).
Claim 53 is indefinite because it pertains to “a method of inhibiting SHP2 activity . . . with a compound of claim 1…” The term “inhibition” is defined as the reduction or suppression of a given condition, activity, effect, symptom, or disorder, or disease, or a significant decrease in the baseline activity of a biological activity or process (page 47 of spec.). It is unclear from the claim language how inhibition will occur “with a compound of claim 1”, since there is no active step in the claim. Examiner suggests introducing active step to specify how the inhibition will be achieved, for example: “a method of inhibiting SHP2 activity . . . comprising administration of a compound of claim 1…” Or something to that effect.
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.
Claims 22 and 41 are 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 22 is rejected for failing to further limit claim 1 from which it depends. Claim 1 defines L1 as -S-, -O-, -C(O)-, or a bond. Claim 22 broadens these limitations to include -S(O)- and -SO2-.
Claim 41 is rejected for failing to further limit claim 40, from which it depends. Claim 40 speaks to the treatment of subjects whose diseases are associated with SHP2. Then, claim 41 expands the method to determining if a disease in the subject is associated with SHP2 (the BRI here entails that a pool of subjects is being tested for the “determining”, some of whom may or may not have an SHP2-associated disease), then administering treatment to compounds whose disease is associated with SHP2.
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.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 41 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a mental process without significantly more.
The claim(s) recites: “determining if the disease in the patient is a SHP2-associated disease, and administering to a subject in need of such treatment a therapeutically effective SHP2 inhibiting amount of a compound of claim 1”. This judicial exception is not integrated into a practical application because, presumably, SHP2 inhibiting treatment is being administered to subjects whose disease was “determined” to have been associated with SHP2. Therefore, subjects whose disease was not “determined” to be associated with SHP2, will presumably receive no SHP2 inhibiting treatment. For this portion of the population, the “determining” step amounts to a mental process without significantly more. In this regard, the claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception.
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.
Claims 1-37, 39-44, and 53 are rejected under 35 U.S.C. 103 as being unpatentable over Ma et al. (WO 2017/211303 A1 – cited in IDS) (“Ma”); in view of Wipf et al. (Obtained from chem.pitt.edu [retrieved on 05/13/2026] <URL: http://ccc.chem.pitt.edu/wipf/courses/5119_08_files/Pharmacy_Lecture_08_HO2.pdf> - Pub. Date: 02/14/2008) (“Wipf”).
Regarding claims 1-37, Ma discloses their compounds of Formula I below as SHP2 inhibitors (abstract) – which is the same intended use as the instant compounds. Ma specifically discloses the compounds 1-2 and 20 below, which read on the instant claims when X1-3 are CH (compounds 1 and 20) or wherein X1 is N and X2-3 are CH (compound 2 – claim 21) ; R2 is Cl; A2 is H; R1 is alkyl (Me); L1 is S; L2 is
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, wherein R19 is -NH2, and X4-6 are N or CH; m = 1 or 2; n = 1 or 2; R3-8 are H, alkyl, amine (corresponding to R9 being NH2 or alkyl – claim 31), or taken together to form a heterocycle (specifically a tetrahydrofuran in compound 1 – claim 13).
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While in Ma’s compounds 1-2 and 20, the group corresponding to instant A1 is -C(O)-C(O)-NH- when the instant claims require (for example) -SO2-NH-C(O)- or -C(O)-NH-SO2- (which corresponds to a -C(O)- being replaced for -SO2- and the position of the nitrogen being changed); Ma also teaches their R3 group in formula I can be
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, which reads on A2 being -N- and A1 being -C(O)-NH-SO2-NH- or -SO2-NH-C(O)-NH-, in view of Wipf (specifically reading on claims 19 and 35).
While Ma doesn’t disclose -SO2- groups in their R3 (corresponding to instant -A1-A2-R1), the teachings of Wipf are relied upon for these disclosures.
Wipf teaches bioisosteres are groups with similar chemical and physical properties, which can attenuate toxicity, modify activity of a lead, or alter pharmacokinetics (slide 1). Wipf discloses -SO2- and -SO2-NR- as a non-classical bioisosteres of -C(O)-.
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Therefore, regarding instant claims 1-37, one having ordinary skill in the art would have found the claimed compounds prima facie obvious, since they are generically embraced by Ma’s disclosed formula and preferred embodiments in view of Wipf; In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). See MPEP 2144.08. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of SHP2 inhibitor compounds disclosed by Ma; in view of Wipf’s teaching that the preparation of bioisosteres can modify activity and other properties of lead compounds, and that -C(O)-, -SO2-, and -SO2-NR- are divalent bioisosteres, which result in similar physical properties. Accordingly, one having ordinary skill in the art would have been motivated to swap a -C(O)- in Ma’s R3 groups for a -SO2- or a -SO2-NR-, as taught by Wipf, to arrive at the instant claims.
Applicant is advised that a novel useful compound that is isomeric with the prior art compound is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compound. In re Norris, 179 F.2d. 970, 84 USPQ 458 (CCPA 1970). Therefore, it would have been obvious to one of ordinary skill to expect similar properties of structurally similar compounds since they are suggestive of one another. It has been held that a compound, which is structurally isomeric with a compound of the prior art, is prima facie obvious absent unexpected results. In re Finely, 81 USPQ 383 (CCPA 1949); 84 USPQ 458 (CCPA 1950).
Regarding claim 39, Ma claims pharmaceutical compositions comprising their compounds and an acceptable excipient (Ma’s claim 72).
Regarding claims 40-44 and 53, Ma claims methods of treating a patient having a condition mediated by SHP2, including Leopard Syndrome (Ma’s claims 80-85). Therefore, it would have been prima facie obvious to one of ordinary skill to administer Ma’s in view of Wipf’s compounds to a subject suffering from an SHP2 mediated condition. One of ordinary skill would have been motivated to do so with a reasonable expectation because of Ma in view of Wipf’s disclosure. Regarding the “determining” of the SHP2-association of the disease, this would have been prima facie obvious to a skilled artisan, since the compounds being administered are specifically disclosed as SHP2 inhibitors. A person with ordinary skill has good reason to pursue known options within his or her technical grasp. Note: MPEP 2143(E) KSR,550 U.S. at 421, 82 USPQ2d at 1397.
Applicant is advised, similar properties may normally be presumed when compounds are very close in structure. Dillon, 919 F.2d at 693, 696, 16 USPQ2d at 1901, 1904. See also In re Grabiak, 769 F.2d 729, 731, 226 USPQ 870, 871 (Fed. Cir. 1985) (“When chemical compounds have very close structural similarities and similar utilities, without more a prima facie case may be made.”). Thus, evidence of similar properties or evidence of any useful properties disclosed in the prior art that would be expected to be shared by the claimed invention weighs in favor of a conclusion that the claimed invention would have been obvious. Dillon, 919 F.2d at 697-98, 16 USPQ2d at 1905; In re Wilder, 563 F.2d 457, 461, 195 USPQ 426, 430 (CCPA 1977); In re Linter, 458 F.2d 1013, 1016, 173 USPQ 560, 562 (CCPA 1972) (see MPEP 2144.08(d)).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACKSON J HERNANDEZ whose telephone number is (571)272-5382. The examiner can normally be reached Mon - Thurs 7:30 to 5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney L. Klinkel can be reached at (571) 270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627
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