INHIBITORS OF THE ONCOGENIC SHP2 PHOSPHATASE AND USES THEREOF

DETAILED ACTION Notice of Pre-AIA or AIA Status The inventor or joint inventor should note that the instant invention, 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 1-5, 11, 14, 16, 18, 25, 51, 52 and 56-63 are pending in the instant invention. According to the Amendments to the Claims, filed September 8, 2026, claims 1, 3, 14, 16, 18, 25, 51, 52, 57-60, 62 and 63 were amended and claims 6-10, 12, 13, 15, 17, 19-24, 26-50, 53-55 and 64-67 were cancelled. Status of Priority This invention is a 35 U.S.C. § 371 National Stage Filing of International Application No. PCT/US2022/050424, filed November 18, 2022, which claims priority under 35 U.S.C. § 119(e) to US Provisional Application No. 63/281,258, filed November 19, 2021. Status of Restrictions / Election of Species PNG media_image1.png 200 400 media_image1.png Greyscale The forthcoming second Office action and prosecution on the merits includes (1) claims 1-5, 11, 14, 16, 18, 25, 51, 52 and 56, drawn to substituted furans of the Formula (I), shown to the right, and/or a pharmaceutical composition thereof; (2) claim 57, drawn to a crystalline form of a substituted furan of the Formula (I), shown to the right above; (3) claim 58, drawn to an amorphous form of a substituted furan of the Formula (I), shown to the right above; (4) claim 59, drawn to a solid form of a substituted furan of the Formula (I), shown to the right above; and (5) claims 60-63, drawn to a method of treating cancer in a patient in need thereof, comprising administering… a substituted furan of the Formula (I), shown to the right above, respectively. Similarly, the inventor or joint inventor should further note that the sections of U.S.C. Title 35 that formed the basis of prior rejections formulated, as well as any references supporting said rejections, that are not included with this Office action, may be found in the Non-Final Rejection, mailed on June 10, 2026. Moreover, the inventor or joint inventor should further note that any rejections and/or objections of record not explicitly addressed herein below, are hereby withdrawn, in light of the inventor’s or joint inventor’s arguments and/or the Amendments to the Claims, filed September 8, 2026. Thus, a second Office action and prosecution on the merits of claims 1-5, 11, 14, 16, 18, 25, 51, 52 and 56-63 is contained within. Status of Claim Rejections - 35 U.S.C. § 112(a) The inventor’s or joint inventor’s arguments, on page 11 of the Remarks, filed September 8, 2026, with respect to claims 60-63, have been fully considered, but are not persuasive. Consequently, the rejection of claims 60-63, made in the Non-Final Rejection, mailed on June 10, 2026, is hereby maintained for the reasons of record. The inventor or joint inventor primarily argues that the specification would enable any person skilled in the art to make and use (perform) the invention commensurate in scope with the claims, without undue experimentation. Similarly, the inventor or joint inventor further argues that an ordinarily skilled artisan would be able to make and use (perform) the claimed invention, despite any experimentation that might be required, in light of the amount of knowledge in the state of the art as well as the predictability of the art. In response to the inventor’s or joint inventor’s argument that (1) the specification would enable any person skilled in the art to make and use (perform) the invention commensurate in scope with the claims, without undue experimentation, and that (2) an ordinarily skilled artisan would be able to make and use (perform) the claimed invention, despite any experimentation that might be required, in light of the amount of knowledge in the state of the art as well as the predictability of the art, the Examiner respectfully disagrees, since [T]he specification must teach how to make and use (perform) the invention, not teach how to figure out for oneself how to make and use (perform) the invention. {See In re Gardner, 166 USPQ 138 (CCPA 1970)}. PNG media_image2.png 200 400 media_image2.png Greyscale Likewise, the inventor’s or joint inventor’s elected invention is directed to a method of treating cancer, comprising administering… a substituted furan of the Formula (I). Based on the guidance provided by the specification and, absent any evidence to the contrary, it is presently unclear whether a substituted furan of the Formula (I), such as N-(4-aminophenyl)-2-hydroxy-5-(5-{[(2Z)-3-oxo-2,3-dihydro-1-benzothiophen-2-ylidene]methyl}furan-2-yl)benzamide, shown to the left above, possesses utility as a therapeutic agent, useful in a method of treating cancer, comprising administering… a substituted furan of the Formula (I). The Examiner requires that the inventor or joint inventor discretely indicate where the specification enables one of ordinary skill in the art to make and use (perform) a method of treating cancer, comprising administering… a substituted furan of the Formula (I), such as that shown above, to overcome this rejection. Next, the inventor or joint inventor should further note that it is well established that [M]ethod of use claims are sufficiently enabled when compounds exhibit a physiological activity and there is a known, reasonable correlation between that physiological activity and the recited conditions. {See Fujikawa v. Wattanasin, 93 F.3d 1559, 39 USPQ2d 1895 (Fed. Cir. 1996); and Cross v. Iizuka, 753 F.2d 1040, 224 USPQ 739 (Fed. Cir. 1985)}. Then, the inventor or joint inventor should further note that [S]ubstantiation of utility and its scope is required when utility is speculative, sufficiently unusual, or not provided. {See Ex parte Jovanovics, 211 USPQ 907, (BPAI 1980); Hoffman v. Klaus, 9 USPQ2d 1657 (BPAI 1988); and Ex parte Powers, 220 USPQ 924 (BPAI 1982)}. In the instant case, the Examiner notes that (1) based on the guidance provided by the specification and, absent any evidence to the contrary, it is presently unclear whether a known, reasonable correlation exists between any physiological activity asserted by the inventor or joint inventor and the breadth of the claims, and that (2) the inventor or joint inventor has failed to establish a reasonable correlation between SHP2 activity and cancer in the instant specification. Moreover, the inventor or joint inventor should further note that the enablement requirement refers to the requirement of 35 U.S.C. § 112(a) that the specification describe how to make and how to use (perform) the invention. The invention that one skilled in the art must be enabled to make and use (perform) is that defined by the claims of the particular invention or patent. Here, the inventor or joint inventor should further note that the purpose of the requirement that the specification describe the invention in such terms that one skilled in the art can make and use (perform) the claimed invention is to ensure that the invention is communicated to the interested public in a meaningful way. The information contained in the disclosure of an invention must be sufficient to inform those skilled in the relevant art how to both make and use (perform) the claimed invention. A patent claim is invalid if it is not supported by an enabling disclosure. Now, the inventor or joint inventor should further note that any analysis of whether a particular claim is supported by the disclosure in an invention requires a determination of whether that disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use (perform) the claimed invention. The standard for determining whether the specification meets the enablement requirement was cast in the Supreme Court decision of Mineral Separation v. Hyde, 242 U.S. 261, 270 (1916) which postured the question: [I]s the experimentation needed to practice the invention undue or unreasonable? That standard is still the one to be applied. {See In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)}. Accordingly, the inventor or joint inventor should further note that [E]ven though the statute does not use the term, undue experimentation, it has been interpreted to require that the claimed invention be enabled so that any person skilled in the art can make and use (perform) the invention, without undue experimentation. {See In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988); and United States v. Telectronics, Inc., 857 F.2d 778, 785, 8 USPQ2d 1217, 1223 (Fed. Cir. 1988)}. Furthermore, the inventor or joint inventor should also note that [O]nce the Examiner has weighed all the evidence and establishes a prima facie case of lack of enablement for the claimed invention, the burden falls on the inventor or joint inventor to present persuasive arguments, supported by suitable proofs where necessary, that one skilled in the art would be able to make and/or use (perform) the claimed invention using the invention as a guide. {See In re Brandstadter, 484 F.2d 1395, 1406-07, 179 USPQ 286, 294 (CCPA 1973)}. Also, the inventor or joint inventor should further note that in order to establish enablement for the claimed invention, factual affidavits or declarations under 37 CFR § 1.132 may be submitted or references illustrating what one skilled in the art knew at the time of filing the invention may be cited. {See In re Buchner, 929 F.2d 660, 661, 18 USPQ2d 1331, 1332 (Fed. Cir. 1991); and MPEP § 2164.05}. As a result of the Amendments to the Claims, filed September 8, 2026, and to clarify the record, the original rejection, made in the Non-Final Rejection, mailed on June 10, 2026, is included below, in the section entitled New Claim Rejections - 35 U.S.C. § 112(a). Status of Claim Rejections - 35 U.S.C. § 112(b) The inventor’s or joint inventor’s arguments, on pages 12-13 of the Remarks, filed September 8, 2026, with respect to claims 57-59, have been fully considered, but are not persuasive. Consequently, the rejection of claims 57-59, made in the Non-Final Rejection, mailed on June 10, 2026, is hereby maintained for the reasons of record. The inventor or joint inventor primarily argues that functional language, alternative expressions, negative limitations, or any style of expression or format of claim which makes clear the boundaries of the subject matter for which protection is sought may be used. Similarly, the inventor or joint inventor further argues that one of ordinary skill in the art viewing the specification would understand that the terms, crystalline, amorphous, and solid, respectively, are definite. In response to the inventor’s or joint inventor’s argument that (1) functional language, alternative expressions, negative limitations, or any style of expression or format of claim which makes clear the boundaries of the subject matter for which protection is sought may be used, and that (2) one of ordinary skill in the art viewing the specification would understand that the terms, crystalline, amorphous, and solid, respectively, the Examiner respectfully disagrees, since 35 U.S.C. § 112(b) requires that the claims particularly point out the subject matter that the inventor or joint inventor regards as the invention. Likewise, the inventor or joint inventor should further note that [A] claim referring to the specification is improper. {See Ex parte Fressola, 27 USPQ 2d 1608 (BPAI 1993)}. Next, the inventor or joint inventor should further note that [W]hen the scope of the claims can’t be determined when considered in light of the specification, a rejection under 35 U.S.C. § 112(b) is proper. {See In re Wiggins, 488 F.2d 538, 179 USPQ 421 (CCPA 1973)}. Then, the inventor or joint inventor should further note that [A]s the statutory language of particular[ity] and distinct[ness] indicates, claims are required to be cast in clear terms, as opposed to ambiguous, vague or indefinite terms. It is the claims that notify the public of what is within the protections of the patent and what is not. {See Merrill v. Yeomans, 94 US 568, 573-74 (1876); United Carbon Co. v. Binney & Smith Co., 317 US 228, 236, 55 USPQ 381 (1942)}. Moreover, the inventor or joint inventor should further note that [T]he USPTO may properly reject a patent invention claim as indefinite for failure to meet statutory requirements of 35 U.S.C. § 112(b) if the PTO identifies ways in which claim language is ambiguous, vague, incoherent, opaque or otherwise unclear in describing and defining the claimed invention, and if the inventor or joint inventor thereafter fails to provide satisfactory response by, for example, modifying language, providing separate definition of unclear language, or, if appropriate, persuasive explanation as to why language is not unclear, since this prima facie case determination is grounded both in the PTO’s responsibility to examine a claim to ensure that it particularly points out and distinctly claims subject matter and in examination’s attendant interactive process. {See In re Packard, 110 USPQ2d 1785 (Fed. Cir. 2014)}. Furthermore, the inventor or joint inventor should also note that [R]ather than requiring that the claims are insolubly ambiguous, we hold that if a claim is amenable to two or more plausible claim constructions, the USPTO is justified in requiring the inventor or joint inventor to more precisely define the metes and bounds of the claimed invention by holding the claim unpatentable under 35 U.S.C. § 112(b) as indefinite. {See Ex Parte Miyazaki, 89 USPQ2d 1207, 1211 (BPAI 2008)}. Also, the inventor or joint inventor should further note that it is well established that the specification may not impose a further limitation upon the plain meaning of the claim language. As stated in the Supreme Court, [S]ome persons seem to suppose that a claim in a patent is like a nose of wax, which may be turned and twisted in any direction by merely referring to the specification, so as to make it include something more than or something different from what its words express. The context may undoubtedly be resorted to, and often is resorted to, for the purpose of better understanding the meaning of the claim, but not for the purpose of changing it and making it different from what it is. The claim is a statutory requirement, prescribed for the very purpose of making the patentee define precisely what his invention is, and it is unjust to the public, as well as an evasion of the law, to construe it in a manner different from the plain meaning of its terms. {See White v. Dunbar, 119 US 47, 51-52, 1886 CD 494, 497-498 (1886)}. As a result of the Amendments to the Claims, filed September 8, 2026, and to clarify the record, the original rejection, made in the Non-Final Rejection, mailed on June 10, 2026, is included below, in the section entitled New Claim Rejections - 35 U.S.C. § 112(b). Status of Claim Rejections - 35 U.S.C. § 112(d) The inventor’s or joint inventor’s arguments, on pages 13 and 14 of the Remarks, filed September 8, 2026, with respect to claims 57-59, 62 and 63, have been fully considered, but are not persuasive. Consequently, the rejection of claims 57-59, 62 and 63, made in the Non-Final Rejection, mailed on June 10, 2026, is hereby maintained for the reasons of record. The inventor or joint inventor primarily argues that one of ordinary skill in the art would readily understand that claims 57-59, 62 and 63 provide additional limitations of the substituted furans of the Formula (I). Similarly, the inventor or joint inventor further argues that claims 57-59, 62 and 63 meet the requirements of 35 U.S.C. § 112(d). In response to the inventor’s or joint inventor’s arguments that (1) one of ordinary skill in the art would readily understand that claims 57-59, 62 and 63 provide additional limitations of the substituted furans of the Formula (I), and that (2) claims 57-59, 62 and 63 meet the requirements of 35 U.S.C. § 112(d), respectively, the Examiner respectfully disagrees, since 35 U.S.C. § 112(d) requires that a dependent claim be rejected, rather than objected to, when the claim fails to further limit the subject matter of the claim upon which it depends, or fails to include all the limitations of the claim upon which it depends. {See Pfizer, Inc. v. Ranbaxy Labs., Ltd., 457 F.3d 1284, 1291-92 (Fed. Cir. 2006); and MPEP § 608.01(n), Section III, Infringement Test for dependent claims}. The inventor or joint inventor should note that a rejection under 35 U.S.C. § 112(d) may be overcome by (1) cancelling the dependent claims, (2) amending the dependent claims to place the dependent claims in proper dependent form, (3) rewriting the dependent claims in independent form, or (4) presenting a sufficient showing that the dependent claims comply with the statutory requirements. As a result of the Amendments to the Claims, filed September 8, 2026, and to clarify the record, the original rejection, made in the Non-Final Rejection, mailed on June 10, 2026, is included below, in the section entitled New Claim Rejections - 35 U.S.C. § 112(d). New Claim Objections Claim 1 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation: A compound of Formula (I): PNG media_image3.png 200 400 media_image3.png Greyscale (I) or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein: Y is -O-; R1 is: PNG media_image4.png 200 400 media_image4.png Greyscale , PNG media_image5.png 200 400 media_image5.png Greyscale , PNG media_image6.png 200 400 media_image6.png Greyscale , or PNG media_image7.png 200 400 media_image7.png Greyscale ; ---- is a single or double bond; A is -CH2-, -O-, or -S-; R9 is H, halogen, NO2, C1-C16 alkyl, C2-C16 alkenyl, C2-C16 alkynyl, C(O)NR13R13, C(O)OR13, C(O)SR13, C(S)OR13, C(S)SR13, NR13R13, OR13, SR13, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, or phenyl, wherein the C1-C16 alkyl, C2-C16 alkenyl, C2-C16 alkynyl, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, or phenyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, amino, and hydroxy; R10 is H, CN, NO2, C1-C16 alkyl, C2-C16 alkenyl, C2-C16 alkynyl, C(O)NR13R13, C(O)OR13, C(O)SR13, C(S)OR13, C(S)SR13, NR13R13, OR13, SR13, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, or phenyl, wherein the C1-C16 alkyl, C2-C16 alkenyl, C2-C16 alkynyl, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, or phenyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, amino, and hydroxy; R11 is H, CN, NO2, C1-C16 alkyl, C2-C16 alkenyl, C2-C16 alkynyl, C(O)NR13R13, C(O)OR13, C(O)SR13, C(S)OR13, C(S)SR13, NR13R13, OR13, SR13, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, or phenyl, wherein the C1-C16 alkyl, C2-C16 alkenyl, C2-C16 alkynyl, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, or phenyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, amino, and hydroxy; or R10 and R11, taken together with the carbon atoms to which they are attached, form a 1,2-phenylene, wherein the 1,2-phenylene is optionally substituted with one or more substituents independently selected from the group consisting of halogen, amino, and hydroxy; R7 is H, halogen, NO2, C1-C16 alkyl, C2-C16 alkenyl, C2-C16 alkynyl, C(O)NR13R13, C(O)OR13, C(O)SR13, C(S)OR13, C(S)SR13, NR13R13, OR13, SR13, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, or phenyl, wherein the C1-C16 alkyl, C2-C16 alkenyl, C2-C16 alkynyl, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, or phenyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, amino, and hydroxy; R8 is H, halogen, NO2, C1-C16 alkyl, C2-C16 alkenyl, C2-C16 alkynyl, C(O)NR13R13, C(O)OR13, C(O)SR13, C(S)OR13, C(S)SR13, NR13R13, OR13, SR13, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, or phenyl, wherein the C1-C16 alkyl, C2-C16 alkenyl, C2-C16 alkynyl, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, or phenyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, amino, and hydroxy; L is a bond; R2 is C(O)NR12R12; R3 is Br or OH; R4 is H, halogen, NO2, C1-C16 alkyl, C2-C16 alkenyl, C2-C16 alkynyl, C(O)NR13R13, C(O)OR13, C(O)SR13, C(S)OR13, C(S)SR13, NR13R13, OR13, SR13, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, or phenyl, wherein the C1-C16 alkyl, C2-C16 alkenyl, C2-C16 alkynyl, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, or phenyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, amino, and hydroxy; R5 is H, halogen, NO2, C1-C16 alkyl, C2-C16 alkenyl, C2-C16 alkynyl, C(O)NR13R13, C(O)OR13, C(O)SR13, C(S)OR13, C(S)SR13, NR13R13, OR13, SR13, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, or phenyl, wherein the C1-C16 alkyl, C2-C16 alkenyl, C2-C16 alkynyl, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, or phenyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, amino, and hydroxy; R6 is H, halogen, NO2, C1-C16 alkyl, C2-C16 alkenyl, C2-C16 alkynyl, C(O)NR13R13, C(O)OR13, C(O)SR13, C(S)OR13, C(S)SR13, NR13R13, OR13, SR13, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, or phenyl, wherein the C1-C16 alkyl, C2-C16 alkenyl, C2-C16 alkynyl, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, or phenyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, amino, and hydroxy; each R12 is independently H, C1-C16 alkyl, C2-C16 alkenyl, C2-C16 alkynyl, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, or phenyl, wherein each C1-C16 alkyl, C2-C16 alkenyl, C2-C16 alkynyl, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, and phenyl is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, amino, and hydroxy; and each R13 is independently C1-C16 alkyl, C2-C16 alkenyl, C2-C16 alkynyl, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, or phenyl, wherein each C1-C16 alkyl, C2-C16 alkenyl, C2-C16 alkynyl, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, and phenyl is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, amino, and hydroxy; with the proviso that the compound of Formula (I) is not: PNG media_image8.png 200 400 media_image8.png Greyscale or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof. Appropriate correction is required. See MPEP § 2173.02. Claim 2 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation: The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R1 is: PNG media_image6.png 200 400 media_image6.png Greyscale . Appropriate correction is required. See MPEP § 2173.02. Claim 3 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation: The compound of claim 2, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R9 is H. Appropriate correction is required. See MPEP § 2173.02. Claim 4 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation: The compound of claim 2, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein A is -O- or -S-. Appropriate correction is required. See MPEP § 2173.02. Claim 5 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation: The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R1 is: PNG media_image9.png 200 400 media_image9.png Greyscale . Appropriate correction is required. See MPEP § 2173.02. Claim 11 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation: The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R3 is OH. Appropriate correction is required. See MPEP § 2173.02. Claim 14 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation: The compound of claim 4, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R10 and R11, taken together with the carbon atoms to which they are attached, form a 1,2-phenylene, wherein the 1,2-phenylene is optionally substituted with one or more substituents independently selected from the group consisting of halogen, amino, and hydroxy. Appropriate correction is required. See MPEP § 2173.02. Claim 16 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation: The compound of claim 4, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein: R10 is H; and R11 is H. Appropriate correction is required. See MPEP § 2173.02. Claim 18 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation: The compound of claim 14, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R9 is H. Appropriate correction is required. See MPEP § 2173.02. Claim 25 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation(s): 25. The compound of claim 1, wherein the compound is selected from the group consisting of: PNG media_image10.png 200 400 media_image10.png Greyscale , PNG media_image11.png 200 400 media_image11.png Greyscale , PNG media_image12.png 200 400 media_image12.png Greyscale , PNG media_image13.png 200 400 media_image13.png Greyscale , PNG media_image14.png 200 400 media_image14.png Greyscale , and PNG media_image2.png 200 400 media_image2.png Greyscale , or a pharmaceutically acceptable salt or tautomer thereof. 68. A compound selected from the group consisting of: PNG media_image15.png 200 400 media_image15.png Greyscale , and PNG media_image16.png 200 400 media_image16.png Greyscale , or a pharmaceutically acceptable salt or tautomer thereof. Appropriate correction is required. See MPEP § 2173.02. Claim 51 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation: The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein: R1 is: PNG media_image17.png 200 400 media_image17.png Greyscale , PNG media_image18.png 200 400 media_image18.png Greyscale , PNG media_image19.png 200 400 media_image19.png Greyscale , or PNG media_image20.png 200 400 media_image20.png Greyscale ; R7 is H, halogen, C1-C6 alkyl, OR13, or SR13, wherein the C1-C6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, amino, and hydroxy; R8 is H, halogen, C1-C6 alkyl, OR13, or SR13, wherein the C1-C6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, amino, and hydroxy; R4 is H, halogen, or C1-C6 alkyl, wherein the C1-C6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, amino, and hydroxy; R5 is H, halogen, or C1-C6 alkyl, wherein the C1-C6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, amino, and hydroxy; R6 is H, halogen, or C1-C6 alkyl, wherein the C1-C6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, amino, and hydroxy; each R12 is independently H, C1-C6 alkyl, or phenyl, wherein each C1-C6 alkyl and phenyl is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, amino, and hydroxy; and each R13 is independently C1-C6 alkyl. Appropriate correction is required. See MPEP § 2173.02. Claim 52 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation: The compound of claim 51, wherein the compound is selected from the group consisting of: PNG media_image13.png 200 400 media_image13.png Greyscale , PNG media_image21.png 200 400 media_image21.png Greyscale , PNG media_image14.png 200 400 media_image14.png Greyscale , and PNG media_image2.png 200 400 media_image2.png Greyscale , or a pharmaceutically acceptable salt or tautomer thereof. Appropriate correction is required. See MPEP § 2173.02. Claim 56 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation: A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof. Appropriate correction is required. See MPEP § 2173.02. Claim 60 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(a), 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation(s): 60. A method for inhibiting src-homology 2 domain-containing phosphatase 2 (SHP2) activity in a patient in need thereof, wherein the method comprises administering to the patient a therapeutically effective dose of a compound of claim 51, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof. 69. The method of claim 60, wherein the patient suffers from cancer. Appropriate correction is required. See MPEP § 2173.02. Claim 61 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation: 70. The method of claim 69, wherein the cancer comprises cells expressing src-homology 2 domain-containing phosphatase 2 (SHP2) that comprises an E76K mutation. Appropriate correction is required. See MPEP § 2173.02. New Claim Rejections - 35 U.S.C. § 112(a) 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. Method of treating cancer, comprising administering… a substituted furan of the Formula (I) Claims 60-63 are rejected under 35 U.S.C. § 112(a) as failing to comply with the enablement requirement because the claims contain subject matter, particularly a method of treating cancer, comprising administering… a substituted furan of the Formula (I), which was not described in the specification in such a way as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use (perform) the invention commensurate in scope with these claims. 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. These factors include, but are not limited to: (a) breadth of the claims; (b) nature of the invention; (c) state of the prior art; (d) level of one of ordinary skill in the art; (e) level of predictability in the art; (f) amount of direction provided by the inventor or joint inventor; (g) existence of working examples; and (h) quantity of experimentation needed to make or use the invention based on the content of the disclosure. {See Ex parte Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986); and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988)}. The above factors, regarding the present invention, are summarized as follows: PNG media_image1.png 200 400 media_image1.png Greyscale (a) Breadth of the claims - the breadth of the claims includes a method of treating cancer, comprising administering… a substituted furan of the Formula (I), shown to the right; (b) Nature of the invention - the nature of the invention is performance of a method of treating cancer, comprising administering… a substituted furan of the Formula (I), shown to the right above; (c) State of the prior art - Nature Reviews: Drug Discovery, as provided in the file and cited in the Non-Final Rejection, mailed on June 10, 2026, offers a snapshot of the state of the drug development art. Herein, drug development is stated to follow the widely accepted Ehrlich model which includes: (1) development of a broad synthetic organic chemistry program; (2) subsequent testing of compounds in an appropriate laboratory model for the disease to be treated; and (3) screening of compounds with low toxicity in prospective clinical trials (Jordan, V. C. Nature Reviews: Drug Discovery, 2, 2003, 205). Similarly, no single drug has been discovered that is effective in treating the myriad of cancers, including, but not limited to, breast cancer and leukemia {See In re Hokum, 226 USPQ 353 (ComrPats 1985)}. Moreover, US 2005/0042674, as cited in the Non-Final Rejection, mailed on June 10, 2026, illustrates the synthesis of substituted furans of the Formula (I), and/or methods of use thereof {Yu, et al. in US 2005/0042674, 2005}; (d) Level of one of ordinary skill in the art - the artisans performing the inventor’s or joint inventor’s method of treating cancer, comprising administering… a substituted furan of the Formula (I) would be a collaborative team of synthetic chemists and/or health practitioners, possessing commensurate degree level and/or skill in the art, as well as several years of professional experience; (e) Level of predictability in the art - Synthetic organic chemistry is quite unpredictable (See In re Marzocchi and Horton 169 USPQ at 367 ¶3). Similarly, it is well established that [T]he scope of enablement varies inversely with the degree of unpredictability of the factors involved, and physiological activity is generally considered to be an unpredictable factor {See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970)}. Moreover, the following excerpt is taken from Hackam, et al. , as provided in the file and cited in the Non-Final Rejection, mailed on June 10, 2026, with respect to the poor replication of animal research in human clinical trials {Hackam, et al. JAMA, 296(14), 2006, 1731-1732}: Only about a third of highly cited animal research translated at the level of human randomized trials. This rate of translation is lower than the recently estimated 44% replication rate for highly cited human studies. Nevertheless, we believe these findings have important implications. First, patients and physicians should remain cautious about extrapolating the findings of prominent animal research to the care of human disease. Second, major opportunities for improving study design and methodological quality are available for preclinical research. Finally, poor replication of even high-quality animal studies should be expected by those who conduct clinical research. (f) Amount of direction provided by the inventor - the invention lacks direction with respect to making and/or using (performing) a method of treating cancer, comprising administering… a substituted furan of the Formula (I); (g) Existence of working examples - the disclosure is insufficient to allow extrapolation of the limited examples to enable performing the instantly recited method of treating cancer, comprising administering… a substituted furan of the Formula (I). Similarly, according to the specification, substituted furans of the Formula (I) are capable of treating a variety of cancers, including, but not limited to, breast cancer and leukemia; however, the specification fails to set forth any convincing in vitro and/or in vivo assays corroborating the alleged activity in association with any cancers, including, but not limited to, breast cancer and leukemia. There is insufficient disclosure to reasonably conclude that the method of treating cancer, comprising administering… a substituted furan of the Formula (I), as recited, would contribute to treatment of any cancers, including, but not limited to, breast cancer and leukemia. Furthermore, the combination of the instant specification and Yu, et al. in US 2005/0042674, as cited in the Non-Final Rejection, mailed on June 10, 2026, lacks adequate credible evidence to support the assertion that a method of treating cancer, comprising administering… a substituted furan of the Formula (I), as recited, would contribute to the prophylaxis of any cancers, including, but not limited to, breast cancer and leukemia, since the inventor or joint inventor has neither provided convincing data for any patient population, nor indicated any art recognized correlation between the disclosed data and the breadth of the claims. Within the specification, [A]t least one specific operative embodiment or example of the invention must be set forth. The example(s) and description should be of sufficient scope as to justify the scope of the claims. Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a chemical compound is stated only as a probability or speculation, the disclosure is not sufficient to support claims identifying the compound by such composition or formula. See MPEP § 608.01(p) and MPEP § 2173.05. PNG media_image2.png 200 400 media_image2.png Greyscale (h) Quantity of experimentation needed to make and/or use (perform) the invention based on the content of the disclosure - predicting whether a recited compound is in fact one that produces a desired physiological effect at a therapeutic concentration and with useful kinetics, is filled with experimental uncertainty, and without proper guidance, would involve a substantial amount of experimentation (Jordan, V. C. Nature Reviews: Drug Discovery, 2, 2003, 205-213). Furthermore, it is unclear, based on the guidance provided by the specification, whether a substituted furan of the Formula (I), such as N-(4-aminophenyl)-2-hydroxy-5-(5-{[(2Z)-3-oxo-2,3-dihydro-1-benzothiophen-2-ylidene]methyl}furan-2-yl)benzamide, shown to the left above, possesses utility as a therapeutic agent, useful in a method of treating cancer, comprising administering… a substituted furan of the Formula (I). Thus, one of ordinary skill in the art, at the time this invention was made, would have an unreasonable expectation of success and undue experimentation in transferring the in vitro and/or in vivo method of treating cancer, comprising administering… a substituted furan of the Formula (I), wherein the cancer, includes, but is not limited to, breast cancer and leukemia, to any patient population. A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the invention was filed, would not have taught one skilled in the art how to make and/or use (perform) the full scope of the claimed invention without undue experimentation. {See In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)}. The determination that undue experimentation would have been needed to make and use the claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached by weighing all the above noted factual considerations. (See In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404). These factual considerations are discussed comprehensively in MPEP § 2164.08 (scope or breadth of the claims), § 2164.05(a) (nature of the invention and state of the prior art), § 2164.05(b) (level of one of ordinary skill), § 2164.03 (level of predictability in the art and amount of direction provided by the inventor or joint inventor), § 2164.02 (the existence of working examples) and § 2164.06 (quantity of experimentation needed to make or use the invention based on the content of the disclosure). Based on a preponderance of the evidence presented herein, the conclusion that the inventor or joint inventor is insufficiently enabled for making and/or using (performing) a method of treating cancer, comprising administering… a substituted furan of the Formula (I) is clearly justified. The examiner suggests amending the claims, particularly as stated in the section above entitled New Claim Objections, to overcome this rejection. New Claim Rejections - 35 U.S.C. § 112(b) The following is a quotation of the second paragraph of 35 U.S.C. § 112: (b) CONCLUSION. The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or joint inventor regards as the invention. Claim 25 is rejected under 35 U.S.C. § 112(b) as being indefinite for failing to set forth the subject matter which the inventor or joint inventor regards as the invention. The inventor or joint inventor should note that claim 25 recites the limitation, The compound of claim 1, wherein the compound is selected from the group consisting of:… (shown centered below), in line 1 of the claim: PNG media_image15.png 200 400 media_image15.png Greyscale and PNG media_image16.png 200 400 media_image16.png Greyscale . Similarly, the inventor or joint inventor should further note that there is insufficient antecedent basis, in claim 1, for this limitation, with respect to the substituted furans of the Formula (I). According to claim 1, the aforementioned species are not substituted furans of the Formula (I), particularly with regard to R3 and/or R12, respectively. The examiner suggests amending the claim, particularly as stated in the section above entitled New Claim Objections, to overcome this rejection. Claim 57 is rejected under 35 U.S.C. § 112(b) as being indefinite for failing to set forth the subject matter which the inventor or joint inventor regards as the invention. The inventor or joint inventor should note that claim 57 recites the physicochemical property, A crystalline form of a compound of claim 1, or a pharmaceutically acceptable salt thereof, in lines 1-2 of the claim. Similarly, the inventor or joint inventor should further note that the aforementioned physicochemical property renders the instant invention ambiguous, vague, incoherent, opaque and/or otherwise unclear to the examiner and fails to meet the statutory requirements of 35 U.S.C. § 112(b), since the limitation merely states a physicochemical property (i.e. crystallinity) without providing any clarity regarding how the physicochemical property is imparted. Likewise, the inventor or joint inventor should further note that the instantly recited crystalline physicochemical property does not appear to emanate from and/or does not appear to be an inherent or salient property of the instantly recited substituted furans of the Formula (I). Next, the inventor or joint inventor should further note that the examiner is uncertain whether the instantly recited substituted furans of the Formula (I) require an additional unrecited component to be admixed therewith, such as a stabilizer, bulking agent, solvent or buffer, to impart the crystalline physicochemical property. Consequently, the inventor or joint inventor should further note that since the instantly recited substituted furans of the Formula (I) incorporate the aforementioned ambiguous, vague, incoherent, opaque and/or otherwise unclear crystalline physicochemical property, the instantly recited substituted furans of the Formula (I) are rendered indefinite under 35 U.S.C. § 112(b), since one of ordinary skill in the art may not reasonably determine the metes and bounds of the instantly recited substituted furans of the Formula (I) due to an inability to establish the metes and bounds encompassed by the crystalline physicochemical property. Moreover, the inventor or joint inventor should further note that [A] claim which omits matter disclosed to be essential to the invention, as described in the specification or in other statements of record, may also be rejected under 35 U.S.C. § 112(a), as not enabling. {See In re Mayhew, 527 F.2d 1229, 188 USPQ 356 (CCPA 1976); and MPEP § 2164.08(c)}. The examiner suggests amending or cancelling the claim, to overcome this rejection. Claim 58 is rejected under 35 U.S.C. § 112(b) as being indefinite for failing to set forth the subject matter which the inventor or joint inventor regards as the invention. The inventor or joint inventor should note that claim 58 recites the physicochemical property, An amorphous form of a compound of claim 1, or a pharmaceutically acceptable salt thereof, in lines 1-2 of the claim. Similarly, the inventor or joint inventor should further note that the aforementioned physicochemical property renders the instant invention ambiguous, vague, incoherent, opaque and/or otherwise unclear to the examiner and fails to meet the statutory requirements of 35 U.S.C. § 112(b), since the limitation merely states a physicochemical property (i.e. morphology) without providing any clarity regarding how the physicochemical property is imparted. Likewise, the inventor or joint inventor should further note that the instantly recited amorphous physicochemical property does not appear to emanate from and/or does not appear to be an inherent or salient property of the instantly recited substituted furans of the Formula (I). Next, the inventor or joint inventor should further note that the examiner is uncertain whether the instantly recited substituted furans of the Formula (I) require an additional unrecited component to be admixed therewith, such as a stabilizer, bulking agent, solvent or buffer, to impart the amorphous physicochemical property. Consequently, the inventor or joint inventor should further note that since the instantly recited substituted furans of the Formula (I) incorporate the aforementioned ambiguous, vague, incoherent, opaque and/or otherwise unclear amorphous physicochemical property, the instantly recited substituted furans of the Formula (I) are rendered indefinite under 35 U.S.C. § 112(b), since one of ordinary skill in the art may not reasonably determine the metes and bounds of the instantly recited substituted furans of the Formula (I) due to an inability to establish the metes and bounds encompassed by the crystalline physicochemical property. Moreover, the inventor or joint inventor should further note that [A] claim which omits matter disclosed to be essential to the invention, as described in the specification or in other statements of record, may also be rejected under 35 U.S.C. § 112(a), as not enabling. {See In re Mayhew, 527 F.2d 1229, 188 USPQ 356 (CCPA 1976); and MPEP § 2164.08(c)}. The examiner suggests amending or cancelling the claim, to overcome this rejection. Claim 59 is rejected under 35 U.S.C. § 112(b) as being indefinite for failing to set forth the subject matter which the inventor or joint inventor regards as the invention. The inventor or joint inventor should note that claim 59 recites the physicochemical property, A solid form of a compound of claim 1, or a pharmaceutically acceptable salt thereof, in lines 1-2 of the claim. Similarly, the inventor or joint inventor should further note that the aforementioned physicochemical property renders the instant invention ambiguous, vague, incoherent, opaque and/or otherwise unclear to the examiner and fails to meet the statutory requirements of 35 U.S.C. § 112(b), since the limitation merely states a physicochemical property (i.e. morphology) without providing any clarity regarding how the physicochemical property is imparted. Likewise, the inventor or joint inventor should further note that the instantly recited solid physicochemical property does not appear to emanate from and/or does not appear to be an inherent or salient property of the instantly recited substituted furans of the Formula (I). Next, the inventor or joint inventor should further note that the examiner is uncertain whether the instantly recited substituted furans of the Formula (I) require an additional unrecited component to be admixed therewith, such as a stabilizer, bulking agent, solvent or buffer, to impart the solid physicochemical property. Consequently, the inventor or joint inventor should further note that since the instantly recited substituted furans of the Formula (I) incorporate the aforementioned ambiguous, vague, incoherent, opaque and/or otherwise unclear solid physicochemical property, the instantly recited substituted furans of the Formula (I) are rendered indefinite under 35 U.S.C. § 112(b), since one of ordinary skill in the art may not reasonably determine the metes and bounds of the instantly recited substituted furans of the Formula (I) due to an inability to establish the metes and bounds encompassed by the solid physicochemical property. Moreover, the inventor or joint inventor should further note that [A] claim which omits matter disclosed to be essential to the invention, as described in the specification or in other statements of record, may also be rejected under 35 U.S.C. § 112(a), as not enabling. {See In re Mayhew, 527 F.2d 1229, 188 USPQ 356 (CCPA 1976); and MPEP § 2164.08(c)}. The examiner suggests amending or cancelling the claim, to overcome this rejection. New Claim Rejections - 35 U.S.C. § 112(d) The following is a quotation of the fourth paragraph of 35 U.S.C. § 112: (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. Claim 57 is rejected under 35 U.S.C. § 112(d) 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. The inventor or joint inventor should note that claim 57 is rejected under 35 U.S.C. § 112(d) because the recitation of a physicochemical property for a compound must result in a further structural limitation in the compound, in order to be further limiting. In the instant dependent claim, the substituted furans of the Formula (I), as recited in claim 1, are crystalline. Consequently, since the physicochemical property of the substituted furans of the Formula (I), as recited in claim 1, whereby the substituted furans of the Formula (I) are crystalline, fails to result in a further structural limitation to the substituted furans of the Formula (I), as recited in claim 1, and/or fails to include all the limitations of the substituted furans of the Formula (I), as recited in claim 1, it is not given patentable weight and thus, renders the instant dependent claim improperly dependent under 35 U.S.C. § 112(d). {See MPEP § 2111.02; and 37 CFR 1.75(c)}. Similarly, the inventor or joint inventor should further note that the U.S. Court of Appeals for the Federal Circuit indicated that although the requirements of 35 U.S.C. § 112(d) are related to matters of form, non-compliance with 35 U.S.C. § 112(d) renders the claim unpatentable just as non-compliance with other subsections of 35 U.S.C. § 112 would. {See Pfizer, Inc. v. Ranbaxy Labs., Ltd., 457 F.3d 1284, 1291-92 (Fed. Cir. 2006)}. Moreover, the inventor or joint inventor should further note that if a dependent claim does not comply with the requirements of 35 U.S.C. § 112(d) the dependent claim should be rejected under 35 U.S.C. § 112(d) as unpatentable rather than objecting to the claim. {See also MPEP § 608.01(n), Section III, Infringement Test for dependent claims}. The examiner suggests the inventor or joint inventor (1) cancel the dependent claim, (2) amend the dependent claim to place the dependent claim in proper dependent form, (3) rewrite the dependent claim in independent form, or (4) present a sufficient showing that the dependent claim complies with the statutory requirements, to overcome this rejection. Claim 58 is rejected under 35 U.S.C. § 112(d) 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. The inventor or joint inventor should note that claim 57 is rejected under 35 U.S.C. § 112(d) because the recitation of a physicochemical property for a compound must result in a further structural limitation in the compound, in order to be further limiting. In the instant dependent claim, the substituted furans of the Formula (I), as recited in claim 1, are amorphous. Consequently, since the physicochemical property of the substituted furans of the Formula (I), as recited in claim 1, whereby the substituted furans of the Formula (I) are amorphous, fails to result in a further structural limitation to the substituted furans of the Formula (I), as recited in claim 1, and/or fails to include all the limitations of the substituted furans of the Formula (I), as recited in claim 1, it is not given patentable weight and thus, renders the instant dependent claim improperly dependent under 35 U.S.C. § 112(d). {See MPEP § 2111.02; and 37 CFR 1.75(c)}. Similarly, the inventor or joint inventor should further note that the U.S. Court of Appeals for the Federal Circuit indicated that although the requirements of 35 U.S.C. § 112(d) are related to matters of form, non-compliance with 35 U.S.C. § 112(d) renders the claim unpatentable just as non-compliance with other subsections of 35 U.S.C. § 112 would. {See Pfizer, Inc. v. Ranbaxy Labs., Ltd., 457 F.3d 1284, 1291-92 (Fed. Cir. 2006)}. Moreover, the inventor or joint inventor should further note that if a dependent claim does not comply with the requirements of 35 U.S.C. § 112(d) the dependent claim should be rejected under 35 U.S.C. § 112(d) as unpatentable rather than objecting to the claim. {See also MPEP § 608.01(n), Section III, Infringement Test for dependent claims}. The examiner suggests the inventor or joint inventor (1) cancel the dependent claim, (2) amend the dependent claim to place the dependent claim in proper dependent form, (3) rewrite the dependent claim in independent form, or (4) present a sufficient showing that the dependent claim complies with the statutory requirements, to overcome this rejection. Claim 59 is rejected under 35 U.S.C. § 112(d) 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. The inventor or joint inventor should note that claim 59 is rejected under 35 U.S.C. § 112(d) because the recitation of a physicochemical property for a compound must result in a further structural limitation in the compound, in order to be further limiting. In the instant dependent claim, the substituted furans of the Formula (I), as recited in claim 1, are solid. Consequently, since the physicochemical property of the substituted furans of the Formula (I), as recited in claim 1, whereby the substituted furans of the Formula (I) are solid, fails to result in a further structural limitation to the substituted furans of the Formula (I), as recited in claim 1, and/or fails to include all the limitations of the substituted furans of the Formula (I), as recited in claim 1, it is not given patentable weight and thus, renders the instant dependent claim improperly dependent under 35 U.S.C. § 112(d). {See MPEP § 2111.02; and 37 CFR 1.75(c)}. Similarly, the inventor or joint inventor should further note that the U.S. Court of Appeals for the Federal Circuit indicated that although the requirements of 35 U.S.C. § 112(d) are related to matters of form, non-compliance with 35 U.S.C. § 112(d) renders the claim unpatentable just as non-compliance with other subsections of 35 U.S.C. § 112 would. {See Pfizer, Inc. v. Ranbaxy Labs., Ltd., 457 F.3d 1284, 1291-92 (Fed. Cir. 2006)}. Moreover, the inventor or joint inventor should further note that if a dependent claim does not comply with the requirements of 35 U.S.C. § 112(d) the dependent claim should be rejected under 35 U.S.C. § 112(d) as unpatentable rather than objecting to the claim. {See also MPEP § 608.01(n), Section III, Infringement Test for dependent claims}. The examiner suggests the inventor or joint inventor (1) cancel the dependent claim, (2) amend the dependent claim to place the dependent claim in proper dependent form, (3) rewrite the dependent claim in independent form, or (4) present a sufficient showing that the dependent claim complies with the statutory requirements, to overcome this rejection. Claim 62 is rejected under 35 U.S.C. § 112(d) 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. The inventor or joint inventor should note that claim 62 is rejected under 35 U.S.C. § 112(d) because the recitation of a physicochemical property of a compound administered within a method from which the claim depends, must result in a patentably distinct methodical step in the recited method, in order to be further limiting. In the instant dependent claim, the substituted furans of the Formula (I) administered within the method of treating cancer, as recited in claim 60, inhibit wild type SHP2. Consequently, since the physicochemical property of the substituted furans of the Formula (I) administered within the instantly recited method of treating cancer, whereby the substituted furans of the Formula (I) administered within the instantly recited method of treating cancer inhibit wild type SHP2, fails to result in a further patentably distinct methodical step in the method of treating cancer, as recited in claim 60, and/or fails to include all the limitations of the method of treating cancer, as recited in claim 60, it is not given patentable weight and thus, renders the instant dependent claim improperly dependent under 35 U.S.C. § 112(d). {See MPEP § 2111.02; and 37 CFR 1.75(c)}. Similarly, the inventor or joint inventor should further note that the U.S. Court of Appeals for the Federal Circuit indicated that although the requirements of 35 U.S.C. § 112(d) are related to matters of form, non-compliance with 35 U.S.C. § 112(d) renders the claim unpatentable just as non-compliance with other subsections of 35 U.S.C. § 112 would. {See Pfizer, Inc. v. Ranbaxy Labs., Ltd., 457 F.3d 1284, 1291-92 (Fed. Cir. 2006)}. Moreover, the inventor or joint inventor should further note that if a dependent claim does not comply with the requirements of 35 U.S.C. § 112(d) the dependent claim should be rejected under 35 U.S.C. § 112(d) as unpatentable rather than objecting to the claim. {See also MPEP § 608.01(n), Section III, Infringement Test for dependent claims}. The examiner suggests the inventor or joint inventor (1) cancel the dependent claim, (2) amend the dependent claim to place the dependent claim in proper dependent form, (3) rewrite the dependent claim in independent form, or (4) present a sufficient showing that the dependent claim complies with the statutory requirements, to overcome this rejection. Claim 63 is rejected under 35 U.S.C. § 112(d) 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. The inventor or joint inventor should note that claim 63 is rejected under 35 U.S.C. § 112(d) because the recitation of a physicochemical property of a compound administered within a method from which the claim depends, must result in a patentably distinct methodical step in the recited method, in order to be further limiting. In the instant dependent claim, the substituted furans of the Formula (I) administered within the method of treating cancer, as recited in claim 60, inhibit SHP2 oncogenic variant E76K. Consequently, since the physicochemical property of the substituted furans of the Formula (I) administered within the instantly recited method of treating cancer, whereby the substituted furans of the Formula (I) administered within the instantly recited method of treating cancer inhibit SHP2 oncogenic variant E76K, fails to result in a further patentably distinct methodical step in the method of treating cancer, as recited in claim 60, and/or fails to include all the limitations of the method of treating cancer, as recited in claim 60, it is not given patentable weight and thus, renders the instant dependent claim improperly dependent under 35 U.S.C. § 112(d). {See MPEP § 2111.02; and 37 CFR 1.75(c)}. Similarly, the inventor or joint inventor should further note that the U.S. Court of Appeals for the Federal Circuit indicated that although the requirements of 35 U.S.C. § 112(d) are related to matters of form, non-compliance with 35 U.S.C. § 112(d) renders the claim unpatentable just as non-compliance with other subsections of 35 U.S.C. § 112 would. {See Pfizer, Inc. v. Ranbaxy Labs., Ltd., 457 F.3d 1284, 1291-92 (Fed. Cir. 2006)}. Moreover, the inventor or joint inventor should further note that if a dependent claim does not comply with the requirements of 35 U.S.C. § 112(d) the dependent claim should be rejected under 35 U.S.C. § 112(d) as unpatentable rather than objecting to the claim. {See also MPEP § 608.01(n), Section III, Infringement Test for dependent claims}. The examiner suggests the inventor or joint inventor (1) cancel the dependent claim, (2) amend the dependent claim to place the dependent claim in proper dependent form, (3) rewrite the dependent claim in independent form, or (4) present a sufficient showing that the dependent claim complies with the statutory requirements, to overcome this rejection. Allowable Subject Matter No claims are allowed. Conclusion The inventor’s or joint inventor’s arguments and/or the Amendments to the Claims, filed September 8, 2026, necessitated the new grounds of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). The inventor or joint inventor is reminded of the extension of time policy as set forth in 37 CFR 1.136(a). A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action. Any inquiry concerning this communication or earlier communications from the Examiner should be directed to DOUGLAS M. WILLIS, whose telephone number is 571-270-5757. The Examiner may normally be reached on Monday thru Thursday from 8:00-6:00 EST. The Examiner is also available on alternate Fridays. If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Mr. Jeffrey Murray, may be reached on 571-272-9023. The fax phone number for the organization where this invention or proceeding is assigned is 571-273-8300. Information regarding the status of an invention may be obtained from Patent Center. For more information about Patent Center, see https://www.uspto.gov/patents/apply/patent-center. Should you have questions on access to Patent Center, contact the Patent Electronic Business Center (PEBC) at 866-217-9197 (toll-free) or ebc@uspto.gov. /DOUGLAS M WILLIS/ Primary Examiner, Art Unit 1624