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 04/27/2022, is a national stage entry of PCT/US2020/057930, filed 10/29/2020, which claims domestic priority to US provisional application numbers 63/047,411, filed 07/02/2020, 63/035,272, filed 06/05/2020, and to 62/928,139, filed 10/30/2019.
Amendments and Claim Status
The following amendment filed on 11/24/2025 is acknowledged and entered.
Claims 3-5, 16, 17, 21, 22, 24, 25, 27, and 29 are amended;
Claims 30-39 are cancelled;
Claims 1, 2, 5-16, 18, 21, 22, and 23-29 remain withdrawn according to 37 CFR § 1.142(b), as being drawn to a non-elected invention and species;
Claims 3, 4, 17, 19, and 20 read on an elected invention and species and are examined on the merits as such;
Claims 1-29 are pending.
Response to arguments
Applicant’s arguments filed 11/24/2025 with respect to the drawing objections, claim objections and claim rejections under 35 U.S.C. §§ 112(a), 102 (a) (1/2), and 103 have been fully considered.
With respect to the objection to the drawings, the correction of the axes label in Figure panels 1 A-C is sufficient to overcome the rejection.
With respect to the rejection of claims 3, 4, 17, 19, and 20 under 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 3 to limit the definitions of L, R9, and R21 resolves the written description rejection. Applicant asserts that the tighter nexus defined by the amended claims is therefore supported by the specification.
Applicant’s argument is found unpersuasive because amending the claims to recite a more limited list of L, R9, and R21 substituents 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. 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. Selectively amending only L, R9, and R21 does not address the long list of substituents which are presently unsupported in the specification, which were identified in the previous rejection. Furthermore, the instantly claimed definitions of L, R9, and R21 still include substituents which are unsupported by the instant specification. Because these unsupported substituents have not been stricken from the instant claims by amendment, or addressed whatsoever in Applicant arguments, the instant claims continue to fail to satisfy the written description requirement. Adequate written description requires a demonstration of possession of the claimed subject matter, and 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.
At present, Applicant is laying claim to compounds which have yet to be synthesized, and whose feasibility of synthesis is not yet been imagined or determined. 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 3, 4, 17, 19, and 20 under 35 U.S.C. § 103 as being unpatentable over Beckwith et al. (WO 2019038717 A1, published February 28, 2019), hereinafter Beckwith, in view of Patani et al, (Chem Rev (1996) 96, pg. 3147-3176, published December 19, 1996), hereinafter Patani the arguments and claim amendments made by Applicant are insufficient to overcome the rejection. The arguments made by applicant are herein addressed as follows.
Applicant argues that Beckwith narrowly defines R3 (corresponding to R23 substituted at X1) is only being hydrogen or “absent,” and therefore does not teach or suggest substitution at that position. Applicant emphasizes that none of the exemplified compounds show substitution at the instantly claimed X1 position. Applicant contends that Beckwith intentionally defined R3 narrowly, allegedly teaching away from further modification.
Applicant’s argument is unpersuasive because the rejection does not rely on Beckwith to explicitly enumerate every possible substituent, rather, Beckwith is relied upon for teaching the core IKZF2-targeting scaffold, and lead compound (I-102). In order to arrive at the examined species, the person of ordinary skill in the art would have reasonably used this already identified scaffold known to target IKZF2, and make a well-established bioisosteric modification routinely employed in rational drug design, as taught by Patani. The absence of exemplified substitutions at a specific position does not teach away, nor does it preclude routine optimization by a person of ordinary skill in the art. Furthermore, Beckwith does not criticize, discredit, or discourage substitution at position R-3. Instead, Beckwith provides and identifies a suitable framework for further optimization.
Applicant argues that Beckwith does not teach a, “lead compound, “and that compound I-102 was arbitrarily selected with the benefit of hindsight. Applicant further argues that Beckwith’s inconsistent biological data – including compounds exhibiting 0% IKZF2 degradation – would have discouraged the skilled artisan from picking compound I-102 is starting point.
Applicant’s argument is found unpersuasive because the prior art reference is not required to expressly label a compound as “lead” in order for it to serve as a proper starting point under §103. Beckwith discloses compounds expressly aimed at targeting IKZF2, and compound I-102 is structurally representative of the disclosed genus, sharing the same biological objective. The presence of a mixture of activity does not negate the compound suitability as a lead. In fact, a person of ordinary skill in the art would be directly motivated to modify said “poorly performing” compounds in order to improve their biological activity. The selection of a compound I-102 is based on structural similarity, and intended biological target, and not on impermissible hindsight.
Applicant contends that Patani does not teach which specific hydrogen atoms should be substituted, that compound I-102 contains numerous not equivalent C-H bonds, and that the unpredictable nature of protein degradation negates a reasonable expectation of success. Applicant further argues that reliance on general medicinal chemistry principles is improper and that structural similarity alone is insufficient support a conclusion of obviousness.
Applicant’s argument is found not persuasive because Patani is not relied upon to identify a specific hydrogen atom by position, rather Patani is relied upon to teach that substitution of any hydrogen with a hydroxyl is a classical, well-established bioisosteric modification, routinely employed in rational drug design to modulate biological activity. With the IKZF2-targeting scaffold provided by Beckwith, and the teaching of well-known hydroxyl substitutions for hydrogen provided by Patani, motivated by the desire to improve biological activity, a person of ordinary skill in the art would determine the position of substitution by routine optimization. For rejection under §103, absolute predictability is not required; only a reasonable expectation of success, which is satisfied by the teachings of both Beckwith and Patani. The rejection therefore relies on more than structural similarity alone, and is supported by well-established medicinal chemistry practices.
Accordingly, the rejection under 35 U.S.C. § 103 is hereby maintained.
With respect to the rejection of claims 3, 4, 17, 19, and 20, on the grounds of provisional nonstatutory double patenting as being unpatentable over claims 1-19 of copending Application No. 18/287,972 (US 20240239785), as well claims 1-14, 16, 18, 20, 22, and 23 of copending Application No. 18/287,347 (US 20240217970), the identification of the differences in the core scaffold is sufficient to overcome the grounds for rejection. Accordingly, the rejections are hereby withdrawn.
With respect to the rejection of claims 3, 4, 17, 19, and 20, on the grounds of provisional nonstatutory double patenting as being unpatentable over claims 1-11 and 13-18, of copending Application No. 18/031,077 (US 20240034723), Applicant’s amendments have necessitated the inclusion of a new reference to address the amendment to the claim limitations. 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 co-pending application teaches compound 17
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which at the instantly claimed position R-3, teaches a hydrogen. Applicant argues that the instant claims have been amended to strike hydrogen from said position, removing the co-pending application from eligibility for nonstatutory double patenting. However, as detailed previously, a person of ordinary skill in the art would have reasonably employed the teachings of Patani to substitute, halogen, or methyl group at the position of hydrogen, by employing routine modification practices known in the field of medicinal chemistry, rendering the instantly claimed compounds obvious over the prior art.
Accordingly, the nonstatutory double patenting rejection is hereby maintained.
Thus, all arguments presented by Applicants have been addressed and are found unpersuasive for the reasons presented herein and in the previous non-final rejection. Applicants are reminded that “attorney argument [is] not the kind of factual evidence that is required to rebut a prima facie case of obviousness.” In re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997). The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965).
Drawings
The drawings filed on 11/24/2025 are found to be in compliance with 37 CFR §§ 1.121 and 1.84, and are hereby accepted.
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 3, 4, 17, 19 and 20 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 3, 4, 17, 19 and 20 of the instant application are drawn to compounds having following substituents:
L is
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R2 is independently selected from the group consisting of hydrogen, amino, cyano, halo, (C1-C6)alkyl, and (C1-C6)haloalkyl;
R3 is independently selected from the group consisting of hydroxyl, cyano, halogen, (C1-C6)alkyl, and (C1-C6)haloalkyl, or R3 and R4, together with the atoms to which they are attached form a (C3-C7)cycloalkyl group or a 4- to 7- membered heterocycloalkyl group, or R3 and R2, together with the atoms to which they are attached form a (C3-C7)cycloalkyl group or a 4- to 7- membered heterocycloalkyl group, wherein said cycloalkyl, heterocycloalkyl is further optionally and independently substituted by one or more, identical or different R15 groups;
R4 and R4' are independently selected from the group consisting of hydrogen, hydroxyl, amino, amido, carbonyl, cyano, halogen, (C1-C6)alkyl, (C1-C6)haloalkyl, (C1-C6)hydroxyalkyl, (C3-C7)cycloalkyl, 4- to 7-membered 5-membered heterocycloalkyl, (C6-C10)aryl, monocyclic or bicyclic 5- to 10-membered heteroaryl, (C2-3-C6)alkenyl, and (C2-C6)alkynyl; wherein said alkyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl is further optionally and independently substituted by one or more, identical or different R15 groups, or R4 and R4' together with the same carbon atom to which they are attached form a spiro (C3-C7)cycloalkyl group or a 4- to 7-membered heterocycloalkyl group, or R4 and R4', when on different carbon atoms, together with the atoms to which they are attached form a (C3-C7)cycloalkyl group or a 4- to 7-membered heterocycloalkyl group, or R4 and R4', when on adjacent atoms, together with the atoms to which they are attached form a (C6-C10)aryl or a 5- or 6-membered heteroaryl; wherein said cycloalkyl, heterocycloalkyl, aryl or heteroaryl is further optionally and independently substituted by one or more, identical or different R15 groups;
R5 and R5' are independently selected from the group consisting of hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)haloalkyl, (C1-C6)hydroxyalkyl, (C3-C7)cycloalkyl, 4- to 7-membered heterocycloalkyl, (C6-C10)aryl, and monocyclic or bicyclic 5- to 10- membered heteroaryl; wherein said alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl is further optionally and independently substituted by one or more, identical or different R15 groups; R6 is optionally substituted aryl or heteroaryl, or wherein R6 is a R7-substituted aryl or a R7-substituted heteroaryl; wherein said R7-substituted aryl or R7-substituted heteroaryl is further optionally and independently substituted by one or more, identical or different R15 groups;
R15 is independently selected from the group consisting of alkyl, alkenyl, alkynyl, halo, haloalkyl, cycloalkyl, heterocycloalkyl, hydroxy, alkoxy, cycloalkoxy, heterocycloalkoxy, haloalkoxy, aryloxy, heteroaryloxy, aralkyloxy, alkyenyloxy, alkynyloxy, amino, alkylamino, cycloalkylamino, heterocycloalkylamino, arylamino, heteroarylamino, aralkylamino, N-alkyl-N-arylamino, N-alkyl-N-heteroarylamino, N-alkyl-N-aralkylamino, hydroxyalkyl, aminoalkyl, alkylthio, haloalkylthio, alkylsulfonyl, haloalkylsulfonyl, cycloalkylsulfonyl, heterocycloalkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aminosulfonyl, alkylaminosulfonyl, cycloalkylaminosulfonyl, heterocycloalkylaminosulfonyl, arylaminosulfonyl, heteroarylaminosulfonyl, N-alkyl-N-arylaminosulfonyl, N-alkyl-N- heteroarylaminosulfonyl, formyl, alkylcarbonyl, haloalkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, carboxy, alkoxycarbonyl, alkylcarbonyloxy, amino, alkylsulfonylamino, haloalkylsulfonylamino, cycloalkylsulfonylamino, heterocycloalkylsulfonylamino, arylsulfonylamino, heteroarylsulfonylamino, aralkylsulfonylamino, alkylcarbonylamino, haloalkylcarbonylamino, cycloalkylcarbonylamino, heterocycloalkylcarbonylamino, arylcarbonylamino, heteroarylcarbonylamino, aralkylsulfonylamino, aminocarbonyl, alkylaminocarbonyl, cycloalkylaminocarbonyl, heterocycloalkylaminocarbonyl, arylaminocarbonyl, heteroarylaminocarbonyl, N-alkyl-N-arylaminocarbonyl, N-alkyl-N- heteroarylaminocarbonyl, cyano, nitro, azido, phosphinyl, phosphoryl including phosphine oxide and phosphonate, cyclic acetal, 4- to 7-membered heterocycloalkyl which contains at least one nitrogen atom and is linked via the nitrogen atom, aryl, heteroaryl, and where two adjacent R15 taken together with the respective atoms to which each is bonded form an aryl, or a heteroaryl, or a 5- to 8-membered cycloalkyl or 5- to 8-membered heterocycloalkyl;
R21 is a (C6-C10)aryl, and a monocyclic or bicyclic 5- to 10-membered heteroaryl; wherein said aryl or heteroaryl is optionally and independently substituted by one or more, identical or different R25 groups;
R22 is selected from the group consisting alkyl, haloalkyl, (C3-C7)cycloalkyl, 4- to 7- membered heterocycloalkyl, (C6-C10)aryl, and monocyclic or bicyclic 5- to 10-membered heteroaryl; wherein said alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl is further optionally and independently substituted by one or more, identical or different R15 groups;
R23 is selected from the group consisting amino, hydroxyl, cyano, halogen, (C1-C6)alkyl and (C1-C6)haloalkyl, or R23 and R4, together with the atoms to which they are attached form a (C3-C7)cycloalkyl group or a 4- to 7-membered heterocycloalkyl group, or R23 and R2, together with the atoms to which they are attached form a (C3-C7)cycloalkyl group or a 4- to 7-membered heterocycloalkyl group, wherein said cycloalkyl, heterocycloalkyl is further optionally and independently substituted by one or more, identical or different R15 groups;
R25 is independently selected from the group consisting of (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C1-C6)haloalkyl, (C1-C6)haloalkoxy, -C(O)R26, -(CH2)0-3C(O)OR26, -C(O)NR26R27, -NR26C(O)R27, -NR26C(O)OR27, -S(O)pNR26R27, -S(O)pR28, (C1-C6)hydroxyalkyl, halogen, -OH, -O(CH2)1-3CN, -(CH2)1-3CN, -(CR29R29')CN, -NH2, CN, -O(CH2)0-1-3(C6-C10)aryl, adamantyl, -O(CH2)0-3-5- or 6-membered heteroaryl comprising 1 to 3 heteroatoms selected from O, N, and S, (C6-C10)aryl, monocyclic or bicyclic 5- to 10- membered heteroaryl, (C3-C7)cycloalkyl, and 4- to 7-membered heterocycloalkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl is further optionally and independently substituted by one or more, identical or different R15 groups, or wherein two R25 groups when on adjacent atoms, together with the atoms to which they are attached form an aryl or a 5- or 6-membered heteroaryl, optionally substituted with one or more R15 groups, or wherein two R25 groups together with the atoms to which they are attached form a (C5-C7) cycloalkyl ring, or a 5- to 7-membered heterocycloalkyl ring, optionally substituted with one or more R15;
R26 and R27 are independently selected from the group consisting of hydrogen and alkyl;
R28 is selected from the group consisting of (C1-C6)alkyl, (C1-C6)haloalkyl, (C3- C7)cycloalkyl, 4- to 7-membered heterocycloalkyl, (C6-C10)aryl and monocyclic or bicyclic 5- to 10-membered heteroaryl; wherein said alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl is further optionally and independently substituted by one or more, identical or different R15 groups;
R29 and R29' are independently selected from the group consisting of R4, provided at least one R29 and R29' together with the same carbon atom to which they are attached form a spiro (C3-C7)cycloalkyl, or R29 and R29', when on adjacent carbon atoms, together with the atoms to which they are attached form a (C3-C7)cycloalkyl; wherein said cycloalkyl is further optionally and independently substituted by one or more, identical or different R15 groups;
n1 is independently 0, 1 or 2;
n6 and n6' are independently 0, 1, 2, 3, 4 or 5, provided that n6 and n6' cannot both be 0;
n7 is 1 or 2; and
p is 0, 1 or 2
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:
L as
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R2 as amino, cyano, halo, (C1-C6)alkyl, and (C1-C6)haloalkyl
R3 as Chloro, Bromo, Iodo, (C2-C6)alkyl, and (C1-C6)haloalkyl, or R3 and R4, together with the atoms to which they are attached form a (C3-C7)cycloalkyl group or a 4- to 7- membered heterocycloalkyl group, or R3 and R2, together with the atoms to which they are attached form a (C3-C7)cycloalkyl group or a 4- to 7- membered heterocycloalkyl group, wherein said cycloalkyl, heterocycloalkyl is further optionally and independently substituted by one or more, identical or different R15 groups;
R4 and R4' are independently selected from the group consisting of hydrogen, hydroxyl, amino, amido, carbonyl, cyano, Chloro, Bromo, Iodo, (C1-C6)alkyl, (C1-C6)haloalkyl, (C1-C6)hydroxyalkyl, (C3-C7)cycloalkyl, 4- to 7-membered 5-membered heterocycloalkyl, (C6-C10)aryl, monocyclic or bicyclic 5- to 10-membered heteroaryl, (C2-3-C6)alkenyl, and (C2-C6)alkynyl; wherein said alkyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl is further optionally and independently substituted by one or more, identical or different R15 groups, or R4 and R4' together with the same carbon atom to which they are attached form a spiro (C3-C7)cycloalkyl group or a 4- to 7-membered heterocycloalkyl group, or R4 and R4', when on different carbon atoms, together with the atoms to which they are attached form a (C3-C7)cycloalkyl group or a 4- to 7-membered heterocycloalkyl group, or R4 and R4', when on adjacent atoms, together with the atoms to which they are attached form a (C6-C10)aryl or a 5- or 6-membered heteroaryl; wherein said cycloalkyl, heterocycloalkyl, aryl or heteroaryl is further optionally and independently substituted by one or more, identical or different R15 groups;
R5 and R5' are independently selected from the group consisting of, (C2-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)haloalkyl, (C1-C6)hydroxyalkyl, (C3-C7)cycloalkyl, 4- to 7-membered heterocycloalkyl, (C6-C10)aryl, and monocyclic or bicyclic 5- to 10- membered heteroaryl; wherein said alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl is further optionally and independently substituted by one or more, identical or different R15 groups; R6 is optionally substituted aryl or heteroaryl, or wherein R6 is a R7-substituted aryl or a R7-substituted heteroaryl; wherein said R7-substituted aryl or R7-substituted heteroaryl is further optionally and independently substituted by one or more, identical or different R15 groups;
R9 as (C3-C6)alkyl, C6 aryl, wherein said alkyl or aryl is further optionally and independently substituted by one or more, identical or different R15 groups;
R15 as alkenyl, alkynyl, Bromo, Iodo, haloalkyl, cycloalkyl, hydroxy, cycloalkoxy, heterocycloalkoxy, aryloxy, heteroaryloxy, aralkyloxy, alkyenyloxy, alkynyloxy, amino, alkylamino, arylamino, heteroarylamino, aralkylamino, N-alkyl-N-arylamino, N-alkyl-N-heteroarylamino, N-alkyl-N-aralkylamino, hydroxyalkyl, aminoalkyl, alkylthio, haloalkylthio, alkylsulfonyl, haloalkylsulfonyl, cycloalkylsulfonyl, heterocycloalkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aminosulfonyl, alkylaminosulfonyl, cycloalkylaminosulfonyl, heterocycloalkylaminosulfonyl, arylaminosulfonyl, heteroarylaminosulfonyl, N-alkyl-N-arylaminosulfonyl, N-alkyl-N-heteroarylaminosulfonyl, formyl, alkylcarbonyl, haloalkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, carboxy, alkoxycarbonyl, alkylcarbonyloxy, amino, alkylsulfonylamino, haloalkylsulfonylamino, cycloalkylsulfonylamino, heterocycloalkylsulfonylamino, arylsulfonylamino, heteroarylsulfonylamino, aralkylsulfonylamino, alkylcarbonylamino, haloalkylcarbonylamino, cycloalkylcarbonylamino, heterocycloalkylcarbonylamino, arylcarbonylamino, heteroarylcarbonylamino, aralkylsulfonylamino, aminocarbonyl, alkylaminocarbonyl, cycloalkylaminocarbonyl, heterocycloalkylaminocarbonyl, arylaminocarbonyl, heteroarylaminocarbonyl, N-alkyl-N-arylaminocarbonyl, N-alkyl-N- heteroarylaminocarbonyl, nitro, azido, phosphinyl, phosphoryl including phosphine oxide and phosphonate, cyclic acetal, 4- to 7-membered heterocycloalkyl which contains at least one nitrogen atom and is linked via the nitrogen atom, aryl, heteroaryl, and where two adjacent R15 taken together with the respective atoms to which each is bonded form an aryl, or a heteroaryl, or a 5- to 8-membered cycloalkyl or 5- to 8-membered heterocycloalkyl;
R21 as a (C7-C10)aryl wherein said aryl is optionally and independently substituted by one or more, identical or different R25 groups;
R22 is selected from the group consisting alkyl, haloalkyl, (C3-C7)cycloalkyl, 4- to 7- membered heterocycloalkyl, (C6-C10)aryl, and monocyclic or bicyclic 5- to 10-membered heteroaryl; wherein said alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl is further optionally and independently substituted by one or more, identical or different R15 groups;
R23 as Chloro, Bromo, Iodo, (C2-C6)alkyl and (C1-C6)haloalkyl, or R23 and R4, together with the atoms to which they are attached form a (C3-C7)cycloalkyl group or a 4- to 7-membered heterocycloalkyl group, or R23 and R2, together with the atoms to which they are attached form a (C3-C7)cycloalkyl group or a 4- to 7-membered heterocycloalkyl group, wherein said cycloalkyl, heterocycloalkyl is further optionally and independently substituted by one or more, identical or different R15 groups;
R25 as (C3-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C2-C6)alkoxy, (C2-C6)haloalkyl, (C2-C6)haloalkoxy, -C(O)R26, -(CH2)0-3C(O)OR26, -C(O)NR26R27, -NR26C(O)R27, -NR26C(O)OR27, -S(O)pNR26R27, -S(O)pR28, (C1-C6)hydroxyalkyl, halogen, -OH, -O(CH2)1-3CN, -(CH2)1-3CN, -(CR29R29')CN, -NH2, CN, -O(CH2)2-3(C7-C10)aryl, adamantyl, -O(CH2)0-3-5- or 6-membered heteroaryl comprising 1 to 3 heteroatoms selected from O, N, and S, (C7-C10)aryl, monocyclic or bicyclic 5- to 10- membered heteroaryl, (C4-C7)cycloalkyl, and 7-membered heterocycloalkyl, wherein said alkyl, cycloalkyl, or heterocycloalkyl, is further optionally and independently substituted by one or more, identical or different R15 groups, or wherein two R25 groups when on adjacent atoms, together with the atoms to which they are attached form an aryl or a 5- or 6-membered heteroaryl, optionally substituted with one or more R15 groups, or wherein two R25 groups together with the atoms to which they are attached form a (C5-C7) cycloalkyl ring, or a 5- to 7-membered heterocycloalkyl ring, optionally substituted with one or more R15;
R26 and R27 as hydrogen or alkyl;
R28 as (C1-C6)alkyl, (C1-C6)haloalkyl, (C3- C7)cycloalkyl, 4- to 7-membered heterocycloalkyl, (C6-Cio)aryl and monocyclic or bicyclic 5- to 10-membered heteroaryl; wherein said alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl is further optionally and independently substituted by one or more, identical or different R15 groups;
R29 and R29' together with the same carbon atom to which they are attached form a spiro (C4-C7)cycloalkyl, or R29 and R29', when on adjacent carbon atoms, together with the atoms to which they are attached form a (C4-C7)cycloalkyl; wherein said cycloalkyl is further optionally and independently substituted by one or more, identical or different R15 groups;
n1 as 2;
n6 and n6' as an integer of 2-5
n7 as 2
p as 0, 1 or 2
The instant specification (pages 34-83) teaches compounds which are characterized as having only the following substituents:
L is
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R2 is H
R3 is NH2, CN, OH, F, CH3
R4 and R4' are Fluoro, alkyl, amido, C1 hydroxyalkyl, C3-cycloalkyl, 5-membered heterocycloalkyl, C6 aryl, monocyclic 5- to 6-membered heteroaryl, (C2-3 alkenyl, or R4 and R4' together with the same carbon atom to which they are attached form a spiro C3 cycloalkyl group, or R4 and R4', when on different carbon atoms, together with the atoms to which they are attached form a C3 cycloalkyl group
R5 and R5’ are H and CH3
R9 is hydrogen, C1-2 alkyl, C6 aryl
R15 is CH3, F, Cl, CF3, cycloalkyl, heterocycloalkyl , OCH3, OCF3, cycloalkylamino, heterocycloalkylamino, cyano
R21 is C6 aryl, and a monocyclic or bicyclic 5- to 6-membered heteroaryl
R22 is not exemplified absent
R23 is NH2, OH, CH3, F, CN
R24 is not exemplified
R25 is C1 alkoxy-O(CH2)0-1-C6aryl, C6 aryl, monocyclic 6-membered heteroaryl, C3 cycloalkyl,4-6-membered heterocycloalkyl
R26 and R27 are not exemplified
R28 is not exemplified
R29 and R29' together with the same carbon atom to which they are attached form a spiro C3 cycloalkyl, or R29 and R29', when on adjacent carbon atoms, together with the atoms to which they are attached form a C3 cycloalkyl
n1 is 0 and 1
n6 and n6' are 0 and 1
n7 is 1
p is not exemplified
Therefore, the compounds described in the instant specification detail only a limited number of the total substituents claimed (see substituents 1-17, above). All working examples presented in the instant specification are related to the compounds containing a fraction of the total claimed substituents (see substituents 18-36, 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 substituents 36-54, above). 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, claims 3, 4, 17, 19, 20 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.
Claim Rejections - 35 U.S.C. § 103
The following is a quotation of pre-AIA 35 U.S.C. § 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 3, 4, 17, 19, and 20 are rejected under 35 U.S.C. § 103 as being unpatentable over Beckwith (see earlier citation), in view of Patani (see earlier citation).
The instant application is drawn to a compound of Formula (II), aimed at the targeting of Ikaros Zinc Finger 2 protein, Helios (IKZF2), a critical factor in restricting T cell effector function. The intended goal of the compound is to elicit and enhance and antitumor immune response by enabling regulatory T cells to assume functions of effector T cells, and by rescuing effector T-cell function in exhausted T cells or CAR-T cells.
Beckwith teaches compounds similarly aimed at targeting Helios (IKZF2), to reduce the levels of the protein in an effort to ameliorate disease or disorder (Abstract). On page 248, Beckwith teaches compound 3-(5-(1 -(3 -methoxybenzyl)piperidin-4-yl)-1 -oxoisoindolin-2-yl)piperidine-2,6-dione, also known as RN 2291363-48-7. [Database Registry Chemical Abstracts Service, Columbus, Ohio, Accession No. RN 2291363-48-7. Entered STN: 21 Mar 2019], as shown in Figure 3.
A nonelected species, compound 261, a compound of Formula (II) is rendered obvious by the prior art compound wherein,
Figure 3. Structural comparison of prior art compound and instantly claimed Formula (II)
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Figure 3. a) Beckwith CAS Registry Number: RN 2291363-48-7 b) instantly claimed compound 261
R2 is H
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R4, R4’, R5, R5’, R23 are H
R21 is C6 aryl
R25 is O-CH3
Wherein R23 is H in the prior art compound, and R23 is OH in the claimed compound 261, this substitution is considered to be a classical bioisosteres, well-known to the ordinary artisan in skilled in rational drug design. With respect to classical Bioisosteres, Patani teaches that the substitution of Hydrogen by Hydroxide is one of the more commonly employed isosteric replacements (page 3149, section II, segment A, item 1 of Patani). This teaching is based on Grimm’s Hydride displacement law (page 3152, section II, segment A, item 4 of Patani), which describes how chemical groups can mimic each other, and is one of the most crucial lead modification tools in rational drug design. Therefore, it would’ve been obvious for a person having ordinary skill in the art prior to the effective filing date to modify the compounds described by Beckwith to substitute Hydroxide in the place of Hydrogen for R23 as taught by Patani, in order to chemically modify the original compounds.
A person of ordinary skill in the art would have a reasonable expectation of success in developing compounds which are more potent inhibitors using these well-known modifications. As such, the claims are rejected.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 3, 4, 17, and 19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 and 13-18, of copending Application No. 18/031,077 (US 20240034723), in view of Patani (see earlier citation). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims as written result in compounds of the same structure as those of the reference application.
The number of compounds which overlap with the instant application are too great to enumerate. However, a compound from the reference application is described below as reading on compound of Formula (II). For example, compound 17 of the reference application
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renders obvious a non-elected species, compound 123, wherein
R2 is H
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R4, R4’, R5, R5’ and R23 are H
R21 is bicyclic C9 heteroaryl
R25 is C6 aryl
However, the co-pending application teaches wherein R3 is H, which has been explicitly stricken from the instant claims.
The deficiencies of the co-pending application are remedied by Patani, who teaches rational approaches in drug design, which encompass substitutions used by those skilled in the art to develop novel and more-potent therapeutics.
Wherein R3 is H in the co-pending application compound, and R3 is amino, hydroxyl, halogen, or CH3 in the instant claims: these substitutions are considered to be classical bioisosteric replacements, well-known to the ordinary artisan in skilled in rational drug design. With respect to classical Bioisosteres, Patani teaches that the substitution of Hydrogen by Methyl, Amino, Halogen, and Hydroxyl are some of of the more commonly employed isosteric replacements (page 3152, section II, segment A, item 4 of Patani). This teaching is based on Grimm’s Hydride displacement law which describes how chemical groups can mimic each other, and is one of the most crucial lead modification tools in rational drug design. Therefore, it would have been obvious for a person having ordinary skill in the art prior to the effective filing date to modify the compounds described by the co-pending application to include any of the instantly claimed substituents in the place of Hydrogen, as taught by Patani on the R3 substituent, in order to chemically modify the original compounds.
Thus, the claims as written, in view of the prior art would result in compounds of the same structure as those of the co-pending application, and the subject matter is overlapping, fully.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. If a notice of allowance is issued in the co-pending application 18/031,077, upon issue of the patent, the provisionary NSDP rejection over the co-pending application will convert to a NSDP rejection over the published patent.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new grounds of rejection presented in this Office action. Accordingly 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