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 .
Priority
The instant application, filed 03/08/2022, is a national stage entry of PCT/CN2020/114253, filed 09/09/2020. Acknowledgment is made of applicant's claim for foreign priority based on an application filed in China (CN201910848926.9) on 09/09/2019. Receipt is acknowledged of certified copies of papers required by 37 CFR § 1.55.
Amendments and Claim Status
The following amendment filed on 11/25/2025 is acknowledged and entered.
Claims 1, 5, 7, 22, and 27 are amended;
Claims 2 and 10-15 are cancelled;
Claims 1, 3-9, and 16-27 are pending and are under prosecution.
Information Disclosure Statement
The Information Disclosure Statement filed on 11/25/2025 is acknowledged and found to be in compliance with the provisions of 37 CFR § 1.97. Accordingly, the information disclosure statement is considered.
Response to arguments
Applicant’s arguments filed 11/25/2025 with respect to the claim objections and claim rejections under 35 U.S.C. §§ 112(a), 112 (b), and 112 (d) have been fully considered.
With respect to the objection to claim 1, the amendment to the claim, reflecting the removal of the duplicate tricyclic moieties, the removal of non-English language symbol, and correction of the subscripts is sufficient to overcome the rejection.
With respect to the objection to claim 5, the amendment to the claim, reflecting the correction of the subscripts is sufficient to overcome the rejection.
With respect to the rejection of Claims 22-25 and 27 are rejected under 35 U.S.C. § 112 (a), scope of enablement, Applicant’s arguments have been fully considered but are not persuasive for the reasons set forth below. The arguments made by Applicant are herein addressed as follows.
Applicant argues that the claimed methods are enabled because the specification discloses compounds that inhibit PD-1/PD-L1 signaling, and a person of ordinary skill in the art would therefore be able to practice the claimed methods of treating cancer, infectious disease, an autoimmune disease.
Applicant’s argument is found unpersuasive because the specification merely details that the compounds instantly claimed are capable of binding to their intended target. However, the binding of a compound to a biological target does not necessarily result in functional inhibition or therapeutic efficacy. The specification does not demonstrate that the claimed compounds inhibit PD-1/PD-L1 signaling to degree sufficient to produce a therapeutic effect for treating cancer, infectious diseases, or autoimmune diseases.
Applicant further argues that because PD-1/PD-L1 inhibitors are known in the art to be involved in immune modulation, a person of ordinary skill in the art would reasonably expect the claimed compounds to treat a broad range of diseases, including the extensive list of cancers, infectious diseases, and autoimmune disease recited in the instant claims.
Applicant’s argument is found unpersuasive because the argument improperly conflates biological plausibility with enablement. Even if a compound is theoretically capable of modulating PD-1/PD-L1 signaling, such capability does not mean the compound will be therapeutically effective for treating each of the claimed diseases. The specification does not teach which diseases are treatable, how efficacy is achieved, or how treatment parameters vary across fundamentally different disease classes. Enablement cannot be based on speculation or generalized expectations arising from target binding.
Accordingly, the specification lacks disease specific data, guidance, or examples demonstrating that the claimed compounds treat each of the recited conditions. Thus the claimed invention cannot be practiced without undue experimentation. Accordingly, claims 22-25 and 27 remain rejected 27 under 35 U.S.C. § 112 (a), and the rejection is hereby maintained.
With respect to the rejection of claims 1, 3-6, 8, 9, and 16-18, and 20-27 under 35 U.S.C. § 112 (a) as failing to comply with the written description requirement, Applicant’s arguments have been fully considered but are not persuasive for the reasons set forth below. The arguments made by Applicant are herein addressed as follows.
The following section of the MPEP is relied upon for the response to Applicant’s arguments. According to MPEP § 2163.02, the standard for determining compliance with the written description requirement is as follows,
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"
Applicant argues that amending claim 1 to explicitly specify a tricyclic structure resolves the written description rejection. Applicant asserts that the tricyclic scaffold is now clearly recited and therefore supported by the specification.
Applicant’s argument is found unpersuasive because amending the claims to recite a tricyclic structure does not cure the written description deficiency, because written description requires possession at the time of filing. Applicant has failed to amend the claims according to the compounds disclosed in the specification. Despite significantly amending the tricyclic moieties represented in the claims, applicant continues to claim tricyclic moieties that are unsupported by the instant specification. At present, the specification does not describe the full scope of compounds claimed, nor does it identify representative species to convey possession of the subject matter as instantly claimed. Specifically, there are a long list of substituents which are not supported by the instant specification, which were identified in the previous rejection. These unsupported substituents have not been stricken from the instant claims by amendment. Written description requires a demonstration of possession of the claimed subject matter. The written description requirement is satisfied only when the specification reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date.
Genentech, 108 F.3d at 1366, states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”.
Accordingly, Applicant has not demonstrated the possession of the claimed compounds as required under 35 U.S.C. § 112 (a). The rejection is therefore maintained. Applicant is invited to amend the claims to correspond to subject matter that is adequately supported by the specification, or to provide persuasive evidence demonstrating possession of the claimed compounds as of the effective filing date.
With respect to the rejection of claims 7, 22-25 and 27 under 35 U.S.C. § 112(b) for lack of antecedent basis, the amendments to Claims 1 and 7 are sufficient to overcome the rejections.
With respect to the rejection of claims 7 under 35 U.S.C. § 112(d), the amendments to Claims 1 and 7 are sufficient to overcome the rejection.
Claim Objections
Claim 7 is objected to because according to 37 CFR § 1.121 (c), amendments must be made by rewriting the entire claim with all changes reflected. That is, the deletion of the compound from the table is entirely improper. In any form of amendment, Applicant is required to strike the subject matter instead of deleting it altogether. At present, the deletion of the various compounds with in the list creates gaps within the table. All gaps with in the table should be removed in order for the table to be continuous.
Claim Rejections - 35 U.S.C. § 112
The following is a quotation of the first paragraph of 35 U.S.C. § 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. § 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 3-6, 8, 9, and 16-18, and 20-27 are rejected under 35 U.S.C. § 112(a) or 35 U.S.C. § 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. § 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1, 3-6, 8, 9, and 16-18, and 20-27 of the instant application are drawn to compounds having following substituents:
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wherein X7, X8 and X10 are each independently CR; X6 is N; X9 and X11 are each independently selected from the group consisting of N and CR; wherein each R is independently selected from the group consisting of H, -CN, trifluoromethyl, -CHF2, -OCF3, -OCHF2, sulfonamido, nitro, hydroxyl, halogen, and substituted or unsubstituted C1-C10 alkyl X7 X8 X9 CR is oCH3, NH2 CF3 ChF2
R1, R2, R3, and Rs are each independently selected from the group consisting of H, -CN, trifluoromethyl, -CHF2, -OCF3, -OCHF2, sulfonamido, nitro, hydroxyl, halogen, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C3-C8 cycloalkyl, CN, hydroxyl, C1-C6 amino, and carboxy:
R1’ is selected from the group consisting of NRdRe, substituted or unsubstituted C1-C6 amino, substituted or unsubstituted -(C1-C6 alkylene)-NH-(1-6 alkylene), substituted or unsubstituted
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R4 is selected from the group consisting of NRdRe, substituted or unsubstituted C1-C6 amino, substituted or unsubstituted -(C1-C6 alkylene)-NH-(1-6 alkylene), substituted or unsubstituted
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wherein, Rb and Rc are each independently
selected from the group consisting of H and substituted or substituted C1-Cs alkyl; or Rb and Rc together with the adjacent N atom form substituted or unsubstituted 3-10 membered heterocyclyl having 1-3 heteroatoms selected from N, S and O, or Rb and Rc together with the adjacent N atom form substituted or unsubstituted 4-10 membered lactam
Rd’ is selected from the group consisting of H, substituted or substituted C1-C6 alkyl, substituted or unsubstituted C3-C10 cycloalkyl, and substituted or unsubstituted C6-C10 aryl; wherein, a hydrogen on a carbon atom of Rb, Rc, and Rd may be each independently substituted by deuterium;
Rd and Re is selected from the group consisting of H and substituted or unsubstituted C1-C6 or Rd and Re together form substituted or unsubstituted 4-10 membered heterocyclyl having 1-3 heteroatoms selected from N, S and O;
"substituted" refers to substitution with one or more substituents selected from the group consisting of halogen, -CH2Cl, -CHCl2, -CCl3, -CH2F, -CHF2, -CF3, oxo (=O), -CN, hydroxyl, amino, C1-C6 alkylamino, carboxyl, -NHAc,
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substituted or unsubstituted group selected from the group consisting of C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, C3-C8 cycloalkyl, halogenated C6-C10 aryl, 5-10 membered heteroaryl with 1-3 heteroatoms selected from N, S and O, 5-10 membered heterocyclyl with 1-3 heteroatoms selected from N, S and O; the substituent is selected from the group consisting of halogen, hydroxyl, carboxyl, oxo, cyano, C1-C6 alkoxy, and C1-C6 alkylamino;
heteroatom is selected from B, P, N, S and O
w is 0, 1, 2, 3, 4, 5, 6
L4 is substituted or unsubstituted C1-C4 alkylene, -S-, -O-, NRf, -S(O)-, and -S(O)2-; wherein, a hydrogen on a carbon atom of the substituted or unsubstituted C1-C4 alkylene may be each independently substituted by deuterium, provided that a structure formed by each L4 is chemically stable;
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is selected from the group consisting of substituted or unsubstituted C3- C10 cycloalkyl, substituted or unsubstituted3-10 membered heterocyclyl having1-3 heteroatoms selected from B, P, N, S, and O, or
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is substituted or unsubstituted 3-8 membered nitrogen containing heterocyclyl, or substituted or unsubstituted 4-10 membered cyclic amido, wherein a hydrogen on the ring forming carbon of 3-8 membered nitrogen containing heterocyclyl, substituted or unsubstituted 4-10 membered cyclic amido may be each independently substituted by deuterium
R7 is substituted or unsubstituted C1-C6 alkyl, -CN, hydroxy, amino, carboxyl, -ORg, -N(Rg)2, -CO-NH-SO2-Rg, -NH-SO2-Rg, - SO2-NH-CO-Rg, -CO2Rg, -CON(Rg)2, -CONHCORg, NRg-CO-N(Rg)2, -NRg-SO2-N(Rg)2;
The hydrogen on a carbon atom of Rf and Rg may be independently substituted by deuterium; wherein, the substituents are selected from the group consisting of halogen, hydroxyl, carboxyl, cyano, and C1- C6 alkoxy
35 U.S.C. 112(a) and the first paragraph of pre-AIA 35 U.S.C. 112 require that the "specification shall contain a written description of the invention ...." This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc); Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1560, 19 USPQ2d 1111,1114 (Fed. Cir. 1991); see also Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920-23, 69 USPQ2d 1886, 1890-93 (Fed. Cir. 2004) (discussing the history and purpose of the written description requirement); In re Curtis, 354 F.3d 1347, 1357, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004) ("conclusive evidence of a claim’s enablement is not equally conclusive of that claim’s satisfactory written description"). The written description requirement has several policy objectives. "[T]he ‘essential goal’ of the description of the invention requirement is to clearly convey the information that an applicant has invented the subject matter which is claimed." In re Barker, 559 F.2d 588, 592 n.4, 194 USPQ 470, 473 n.4 (CCPA 1977). Another objective is to convey to the public what the applicant claims as the invention. See Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1566, 43 USPQ2d 1398, 1404 (Fed. Cir. 1997), cert, denied, 523 U.S. 1089 (1998). "The ‘written description’ requirement implements the principle that a patent must describe the technology that is sought to be patented; the requirement serves both to satisfy the inventor’s obligation to disclose the technologic knowledge upon which the patent is based, and to demonstrate that the patentee was in possession of the invention that is claimed." Capon v. Eshhar, 418 F.3d 1349, 1357, 76 USPQ2d 1078, 1084 (Fed. Cir. 2005). Further, the written description requirement promotes the progress of the useful arts by ensuring that patentees adequately describe their inventions in their patent specifications in exchange for the right to exclude others from practicing the invention for the duration of the patent’s term.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
An applicant shows 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. Amer. 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 applicant was in possession of the claimed invention. See, e.g., Pfaffv. Wells Bees., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); EliLilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm.,927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991). An application specification may show actual reduction to practice by describing testing of the claimed invention.
In the present case, the important factors leading to a conclusion of inadequate written description is the absence of any working example of the invention as claimed, and the lack of predictability in the art.
In the instant specification, there is no disclosure of compounds having the following claimed substituents:
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n as 3
m as 2, 3, or 4
p as 2, 3, or 4
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wherein X7, X8 and X10 are each independently CR; X6 is N; X9 and X11 are each independently selected from the group consisting of N and CR; wherein each R is independently selected from the group consisting of -CN -OCF3, -OCHF2, sulfonamido, hydroxyl, halogen, and substituted or unsubstituted C1-C10 alkyl
R1, R2, and R3, as trifluoromethyl, -CHF2, -OCF3, -OCHF2, sulfonamido, nitro, hydroxyl, Fluoro, Iodo substituted or unsubstituted C2-C10 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkoxy, substituted or unsubstituted C3-C8 cycloalkyl, CN, hydroxyl, C1-C6 amino, and carboxy
R5 as sulfonamido, nitro, hydroxyl, Fluoro, Bromo, Iodo, substituted or unsubstituted C2-C10 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkoxy, substituted or unsubstituted C3-C8 cycloalkyl, CN, hydroxyl, C1-C6 amino, and carboxy
R1’ as substituted or unsubstituted -(C1-C6 alkylene)-NH-(1-6 alkylene), substituted or unsubstituted
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wherein, Rb and Rc are each independently selected from the group consisting of H and substituted or substituted C3-Cs alkyl; or Rb and Rc together with the adjacent N atom form substituted or unsubstituted 3-10 membered heterocyclyl having 1-3 heteroatoms selected from S and O, or Rb and Rc together with the adjacent N atom form substituted or unsubstituted 4-10 membered lactam
R4 as substituted or unsubstituted -(C1-C6 alkylene)-NH-(1-6 alkylene), substituted or unsubstituted
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and
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wherein, Rb and Rc are each independently selected from the group consisting of H and substituted or substituted C3-Cs alkyl; or Rb and Rc together with the adjacent N atom form substituted or unsubstituted 3-10 membered heterocyclyl having 1-3 heteroatoms selected from S and O, or Rb and Rc together with the adjacent N atom form substituted or unsubstituted 4-10 membered lactam
Rd’ is selected from the group consisting of H, substituted or substituted C1-C6 alkyl, substituted or unsubstituted C3-C10 cycloalkyl, and substituted or unsubstituted C6-C10 aryl; wherein, a hydrogen on a carbon atom of Rb, Rc, and Rd may be each independently substituted by deuterium;
Rd and Re as substituted or unsubstituted C3-C6 or Rd and Re together form substituted or unsubstituted 4-10 membered heterocyclyl having 1-3 heteroatoms selected from N, S and O;
"substituted as Iodo, -CH2Cl, -CHCl2, -CCl3, -CH2F, -CHF2, -CF3, oxo (=O), -CN, C1-C6 alkylamino, carboxyl, -NHAc,
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substituted or unsubstituted group selected from the group consisting of C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, C3-C8 cycloalkyl, halogenated C6-C10 aryl, 5-10 membered heteroaryl with 1-3 heteroatoms selected from N, S and O, 5-10 membered heterocyclyl with 1-3 heteroatoms selected from N, S and O; the substituent is selected from the group consisting of halogen, hydroxyl, carboxyl, oxo, cyano, C1-C6 alkoxy, and C1-C6 alkylamino;
heteroatom as B, P, and S
w as 0, 2, 3, 4, 5, 6
m as 0 or 2,
L4 is substituted or unsubstituted C1-C4 alkylene, -S-, -O-, NRf, -S(O)-, and -S(O)2-; wherein, a hydrogen on a carbon atom of the substituted or unsubstituted C1-C4 alkylene may be each independently substituted by deuterium, provided that a structure formed by each L4 is chemically stable;
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is selected from the group consisting of substituted or unsubstituted C3-C10 cycloalkyl, substituted or unsubstituted 3-4 or 6-10 membered heterocyclyl having 1-3 heteroatoms selected from B, P, S, and O, or 2-3 heteroatoms selected from N or
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is substituted or unsubstituted 3-8 membered nitrogen containing heterocyclyl, or substituted or unsubstituted 4-10 membered cyclic amido, wherein a hydrogen on the ring forming carbon of 3-8 membered nitrogen containing heterocyclyl, substituted or unsubstituted 4-10 membered cyclic amido may be each independently substituted by deuterium
R7 as substituted or unsubstituted C1-C6 alkyl, -CN, amino, carboxyl, -ORg, -N(Rg)2, -CO-NH-SO2-Rg, -NH-SO2-Rg, - SO2-NH-CO-Rg, -CON(Rg)2, -CONHCORg, NRg-CO-N(Rg)2, -NRg-SO2-N(Rg)2;
The instant specification (pages in 12-69) teaches compounds which are characterized as having only the following substituents:
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R1 is
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R1’ is
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wherein Rb and Rc together with the adjacent N atom form substituted 4-5 membered heterocyclyl wherein Rb and Rc are H, CH3, and substituted C1 and C2 alkyl
R4 is
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wherein Rb and Rc together with the adjacent N atom form substituted 4-5 membered heterocyclyl Rb and Rc are H, CH3, and substituted C1 and C2 alkyl
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as
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X7, X8 and X10 are each independently CR; wherein each R is H OCH3 NO2 CF3 CHF2
R1, R2, and R3 are CH3, OCH3, Cl, and CN
R5 is NO2 CN OCF3 OCHF2 Cl CF3 O
Rd’ is not exemplified
Rd is H and substituted or unsubstituted C1-C2 alkyl
Re is H and substituted or unsubstituted C1-C2 alkyl
"substituted is C1 alkyl, hydroxyl, amino Cl
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CCl3, -CH2F, -CHF2, -CF3
hetero atom is N and O
w is 1
m is 1
L4 is C1 alkylene
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is selected 5-membered heterocyclyl having 1 heteroatom as N,
R7 is hydroxy and -CO2Rg,
Therefore, the compounds described in the instant specification detail only a limited number of the total substituents claimed (see substituents 1-18, above). All working examples presented in the instant specification are related to the compounds containing a fraction of the total claimed substituents (see substituents 38-57, above).
There are no working examples in the instant specification for the wide range of substituents claimed, but for which evidence of possession has not been provided (see 19-36). Thus the instant specification does not provide any evidence that Applicant was in possession of the claimed invention prior to the effective filing of the instant application.
Vas-Cath Inc. Mahurkar, 19 USPQ2d 1111, makes clear the "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116).
Finally, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 held that: ...To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F. 3d 1565, 1572, 41 USPQ2d 1961, 1966(1997); In re Gosteli, 872 F.2d 1008, 1012,10 USPQ2d 1614, 1618 (Fed Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.") Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.
It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. For inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession. For example, disclosure of only a method of making the invention and the function may not be sufficient to support a product claim other than a product-by-process claim. See, e.g., Fiers v. Revel, 984 F.2d at 1169, 25 USPQ2d at 1605; Amgen, 927 F.2d at 1206, 18 USPQ2d at 1021.
Thus, since Applicant has not described in adequate detail methods to synthesize compounds containing the claimed substituents, or provided evidence that said compounds have been characterized, or that they exist, an ordinary skilled artisan could not completely envisage Applicants’ invention. Moreover, it is clear that the written description requirement has not been met since Applicant has not provided any evidence that Applicant was in possession of the claimed invention prior to the effective filing of the instant application. Thus, the cited claims of the instant application are not supported by the instant specification and thus a rejection under 35 U.S.C. § 112 (a) for failing to comply with the written description requirement is proper.
Claims 22-25 and 27 are rejected under 35 U.S.C. § 112 (a), or 35 U.S.C. § 112 (pre-AIA ) first paragraph, because the specification, while being enabling for administering a compound of Formula (I) for the inhibition of PD-1/PD-L1 by a compound of Formula (I), it does not reasonably provide enablement for the treatment of diseases related to the activity or expression of PD-1/PD-L1. The specification does not provide sufficient information to support the claims that PD-1/PD-L1 inhibition by a compound of Formula (I) will lead to the treatment of any disease as claimed.
The instant specification fails to provide information that would allow the skilled artisan to fully practice the instant invention without undue experimentation. Attention is directed to In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight 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. All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the invention: Claims 22-25 and 27of the instant application are drawn to the treatment of diseases related to the activity or expression of PD-1/PD-L1 comprising the administration of a compound of claim 1, including the combination with a therapeutic agent. The claims encompass treating a large range of diseases, infections, and cancers.
Breadth of the claims: The complex nature of the subject matter of this invention is greatly exacerbated by the breadth of the claims. The rejected claims are extremely broad. Applicant claims that the claimed compounds can be used to treat a range of diseases, infections, and cancers. Thus the cited claims are deemed very broad since these claims read on treating all the cancers/diseases characterized by to the activity or expression of PD-1/PD-L1, which includes numerous diseases.
State of the Prior Art: There are no art recognized methods that could be used to establish that the instantly claimed diseases can be commonly addressed using the claimed therapeutic method.
Regarding the mechanisms of diseases related to PD-1/PD-L1, Kuol et al. (Immunotherapy, Vol 10, Issue 2, pg. 149-160, published Dec 20, 2017), hereinafter Kuol, teaches the role of the PD-1/PD-L1 pathway is unclear when examined across many disease manifestations. For instance, Kuol teaches the implication of the PD-1/PD-L1 pathway in autoimmunity, neurological disorders, inflammatory bowel disease, stroke, and cancer (abstract and pages 150-153). Although these diseases and disorders commonly implicate the PD-1/PD-L1 pathway, Kuol highlights the key differences between the roles that the PD-1/PD-L1 pathway play in such diseases. For instance, it is disclosed that the PD-1/PD-L1 pathway acts as protective in autoimmune diseases and stroke but causes exacerbation in cancer (page 153, paragraph 1). Simply put, the common PD-1/PD-L1 pathway may act as antagonistic or as a defense mechanism depending on the disorder or disease. Kuol teaches wherein PD-1 is downregulated in autoimmunity, upregulation of PD-L1 and the interaction of PD-L1 on cancer cells with PD-1 on T cells results in anergy of T cells (page 156, paragraph 1). Therefore, the use of a single therapeutic used as a particular therapy for any disease or disorder related to activity or expression of PD-1/PD-L1 is unpredictable, and requires individualized therapeutic mechanisms that target the myriad manifestations of the PD-1/PD-L1 pathway in a specific disease or disorder.
Predictability/Unpredictability in the Art: It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. In the instant case, the instant claimed invention is highly unpredictable since one skilled in the art would recognize that the recitation encompasses administering a compound of claim 1 to the list of diseases, infections, and cancers and thus encompass the treatment of a vast number of diseases. Thus, the skilled artisan would view that the treatment of all diseases, infections, and cancers encompassed by the claims, by administering a compound of Formula (I) is highly unpredictable.
Moreover, one of skill in the art would recognize that it is highly unpredictable in regard to therapeutic effects, side effects and toxicity generated by administering a singular class of compounds for treating all the disorders and diseases encompassed by the claims.
Guidance of the Specification/Working Examples: Applicant has only provided working examples suggesting that compounds of claim 1 may inhibit PD-1/PD-L1 (pages 69-71 of the instant specification). No working examples for the claimed subject matter of treating a disease related to PD-1/PD-L1 activity or expression has been provided in the specification. Thus, the specification fails to provide sufficient evidence in support of the broad treatment of all the disorders and diseases as recited in the instant claims.
The Quantitation of Experimentation Required: In order to practice Applicants invention, it would be necessary for one to design and conduct an exhaustive amount of complex experiments to demonstrate that the large range of diseases, cancers, and infections can be treated by the administration of the compounds claimed. Therefore, in order to practice the claimed invention, the amount of experimentation required would be considered undue and burdensome.
In conclusion, Genentech, 108 F.3d at 1366, states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”. A method for treating a disease or disorder related to the expression or activity of PD-1/PD-L1 comprising the administration of a compound of Formula (I) to a subject having all the diseases, cancers, and infections claimed is not enabled by the instant specification.
Conclusion
Claims 1, 3-6, 8, 9, 16-18, and 20-27 are rejected.
Claim 7 is objected to.
Claim 19, as previously indicated, is allowable.
THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant 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 nonprovisional extension fee (37 CFR § 1.17(a)) 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 mailing date of this final action.
Correspondence
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/SOPHIA P HIRAKIS/Examiner, Art Unit 1623
/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623