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 .
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 106 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 106 recites, “a compound of: […] (R)-N-(l-(3-bromophenyl)ethyl)-6-methoxy-2-methyl-7-((7-(trityloxy)heptyl)oxy)quinazolin-4-amine A42. (R)-N-(l-(3-bromophenyl)ethyl)-6-methoxy-2-methyl-7-((7-(pyridin-4-yl)heptyl)oxy)quinazolin-4-amine A 43;.” Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations. See Fressola v. Manbeck, 36 USPQ2d 1211 (D.D.C. 1995). (MPEP 608.01(m)). Thus, the use of a period after A42 renders the claim indefinite because it is unclear whether the recitation after the period is included within the claim or not. For example, the claim recites (R)-N-(l-(3-bromophenyl)ethyl)-6-methoxy-2-methyl-7-((7-(trityloxy)heptyl)oxy)quinazolin-4-amine A42. Are only compounds listed from A42 and above included with the scope of the claim or does the claim encompass the listed compounds from D1? As a consequence, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Specifically one of ordinary skill in the art would not be reasonably apprised of what compounds are included within the scope of claim 106 and which are not. Therefore, given the uncertainty around the meaning of the period within claim 106; claim 106 is rejected under 35 U.S.C. 112(b).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 4, 17, 95, 107, and 112, are rejected under 35 U.S.C. 103 as being unpatentable over Patent Application Publication US 2019/0358230 A1 to Gmachl et. al. (Gmachl’230; cited on the IDS) in view of Troup et. al. ((2020), Current strategies for the design of PROTAC linkers: a critical review, Explor Target Antitumor Ther., 1, 273 – 312).
Regarding claims 1, 4, 17, 95, 107, and 112, Gmachl’230 teach new benzylamino substituted quinazolines and derivatives of formula (I)
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and their use as inhibitors of SOS1. See page 1 paragraph 0001. Specifically, Gmachl’230 teach compound number I-288 of
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where instant V = -C(R4)= and instant R4 = -L-RB where instant L = piperidine and instant RB = isopropyl; instant U = X = Y = -C(R5)= where instant R5 = H and CH3; instant R1 = CH3; instant R3 = H; instant R2a = H; instant R2b = CH3; and instant R2c = m-CH3-Phenyl. See page 159 Table 47 Row 1. See claims 1, 4, 17, and 95. Moreover, Gmachl’230 teach compound number I-288 has an IC50 against SOS1 of 22 nM. See page 159 Table 47 Row 1. See claim 112. Furthermore, Gmachl’230 teach the compounds of this disclosure which include compound I-288 can be formulated by with known excipients such as inert diluents, carriers, disintegrants, adjuvants, surfactants, binders and/or lubricants. See page 197 paragraph 1298. See claim 107.
However, Gmachl’230 is silent about whether piperidine is a linker. See claim 1.
Nevertheless, Troup et. al. teach that proteolysis targeting chimeras (PROTACs) are heterobifunctional molecules consisting of two ligands connected by a linker. See page 274 paragraph 1. Furthermore, Troup et. al. teach that PROTACs act as adapter molecules between the E3 ligase and any chosen POI, hijacking the activity of the cell’s natural protein degradation machinery, i.e. the ubiquitin-proteasome system (UPS).See page 274 paragraph 1. Specifically, Troup et. al. teach piperidine as a linker motif that represent about 4 % occurrence rate in maple database structures. See page 279 Table 1. Moreover, Troup et. al. teach that heterocyclic scaffolds (e.g., piperazine/piperidines) and alkynes impart some rigidity and the incorporation of functional groups which are able to modulate PROTAC physico-chemical properties. See page 283 paragraph 1. Additionally, Troup et. al. teach an example where the replacement of the amine linkage to lenalidomide (11) with a rigid ethynyl group led to highly potent PROTAC QCA570 which displayed 3 and 6-fold increased cell activity compared to compound 48 in MOLM13 and MV4;11 cells respectively, but with a 27-fold potency decrease in the RS4;11 cell line. See page 283 paragraph 1 and page 284 Figure 9.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to use the compound of Gmachl’230 with instant L as a piperidine in view of Troup et. al.. One of ordinary skill in the art would have been motivated to make this modification to impart some rigidity and the incorporation of functional groups which are able to modulate PROTAC physico-chemical properties in the pursuit of improved SOS1 inhibitors. One of ordinary skill in the art would have had a reasonable expectation of success because in an example where an amine linkage was replaced with a rigid ethynyl group, there was a 3 and 6-fold increase in cell activity compared to compound 48 with an unrigid amine linkage.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Patent Application Publication US 2019/0358230 A1 to Gmachl et. al. (Gmachl’230; cited on the IDS) in view of Patani et. al. ((1996), Bioisosterism A rational approach in drug design, Chem. Rev., 96, 3147-3176).
The teachings of Gmachl’230 as they relate to claim 1, from which claim 11 depends, is given previously in this office action and are fully incorporated here.
However, Gmachl’230 fails to teach a compound where instant U, X, and Y are each -C(R5)=; V is -N(R4)-; and R4 is -L-RB. See claim 11.
Nevertheless, Patani et. al. teach that the concept of bioisosterism represents one approach used by the medicinal chemist for the rational modification of lead compounds into safer and more clinically effective agents. See page 3147 column 1 paragraph 1 and column 2 paragraph 1. Furthermore, Patani et. al. teach the ability of a group of bioisosteres to elicit similar biological activity has been attributed to common physicochemical properties. See page 3148 column 1 paragraph 2. Moreover, Patani et. al. teach that bioisosteres have been classified as either classical or nonclassical with classical bioisosteres have been traditionally divided into several distinct categories: (A) monovalent atoms or groups; (B) divalent atoms or groups; (C) trivalent atoms or groups; (D) tetrasubstituted atoms; and (E) ring equivalents. See page 3148 column 2 paragraph 4 and page 3149 column 1 paragraph 1. Specifically, Patani et. al. teach the trivalent substitution of -CH= with -N= is commonly used in modern drug design. See page 3159 column 2 paragraph 4. Moreover, Patani et. al. teach an example where a trivalent ring substitution of -CH= with -N= in the antibacterial agent norfloxacin (56a) resulted in enoxacin (56b, Figure 38) which is also in clinical use for its antibacterial activity. See page 3159 column 2 paragraph 4.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to modify prior art compound number I-288 of Gmachl’230 in view of Patani et. al. that is to have a trivalent ring substitution of instant V from -CH= to -N=. One of ordinary skill in the art would have been motivated to make this modification to rationally modify compound number I-288 safer and more clinically effective agent. One of ordinary skill in the art would have had a reasonable expectation of success because the trivalent substitution of -CH= with -N= is commonly used in modern drug design. Moreover, in the prior art example where a trivalent ring substitution of -CH= with -N= in the antibacterial agent the bioisostere was also exhibited favorable biological affect.
Claims 12 – 13, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Patent Application Publication US 2019/0358230 A1 to Gmachl et. al. (Gmachl’230; cited on the IDS) in view of Patani et. al. ((1996), Bioisosterism A rational approach in drug design, Chem. Rev., 96, 3147-3176).
The teachings of Gmachl’230 as they relate to claim 1, from which claims 12 – 13, and 15 depend, is given previously in this office action and are fully incorporated here.
However, Gmachl’230 fails to teach a compound where U and Y are each -C(R5)=; V is -N=; X is -C(R4)= ; and R4 is -L-RB. See claim 12. Additionally, Gmachl’230 fails to teach a compound where U and X are each -C(R5)=; V is -N=; Y is -C(R4)= ; and R4 is -L-RB. See claim 13. Moreover, Gmachl’230 fails to teach a compound where U and X are each -C(R5a)=; V is -N=; X is -C(R5c)= ; Y is -C(R5d)= ; and R4 is -L-RB. See claim 15.
Nevertheless, one of the only difference between the prior art compound species number I-288 of
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where instant V = -C(R4)= and instant R4 = -L-RB where instant L = piperidine and instant RB = isopropyl; instant U = X = Y = -C(R5)= where instant R5 = H and CH3; instant R1 = CH3; instant R3 = H; instant R2a = H; instant R2b = CH3; and instant R2c = m-CH3-Phenyl and the compounds of the instant application as recited in claims 12 – 13,and 15 is the location of the linker on the ring. Thus since the one of the only differences between the instant application and the prior art compound number I-288 is the position of the linker, both the prior art compound number I-288 and the instant application compounds are positional isomers. Hence for position isomers (compounds having the same radicals in physically different positions on the same nucleus) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See MPEP 2144.09(II).
However, Gmachl’230 fails to teach a compound where V is -N=. See claims 12 – 13, and 15.
Nevertheless, Patani et. al. teach that the concept of bioisosterism represents one approach used by the medicinal chemist for the rational modification of lead compounds into safer and more clinically effective agents. See page 3147 column 1 paragraph 1 and column 2 paragraph 1. Furthermore, Patani et. al. teach the ability of a group of bioisosteres to elicit similar biological activity has been attributed to common physicochemical properties. See page 3148 column 1 paragraph 2. Moreover, Patani et. al. teach that bioisosteres have been classified as either classical or nonclassical with classical bioisosteres have been traditionally divided into several distinct categories: (A) monovalent atoms or groups; (B) divalent atoms or groups; (C) trivalent atoms or groups; (D) tetrasubstituted atoms; and (E) ring equivalents. See page 3148 column 2 paragraph 4 and page 3149 column 1 paragraph 1. Specifically, Patani et. al. teach the trivalent substitution of -CH= with -N= is commonly used in modern drug design. See page 3159 column 2 paragraph 4. Moreover, Patani et. al. teach an example where a trivalent ring substitution of -CH= with -N= in the antibacterial agent norfloxacin (56a) resulted in enoxacin (56b, Figure 38) which is also in clinical use for its antibacterial activity. See page 3159 column 2 paragraph 4.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to modify prior art compound number I-288 of Gmachl’230 in view of Patani et. al. that is to have a trivalent ring substitution of instant V from -CH= to -N=. One of ordinary skill in the art would have been motivated to make this modification to rationally modify compound number I-288 safer and more clinically effective agent. One of ordinary skill in the art would have had a reasonable expectation of success because the trivalent substitution of -CH= with -N= is commonly used in modern drug design. Moreover, in the prior art example where a trivalent ring substitution of -CH= with -N= in the antibacterial agent the bioisostere was also exhibited favorable biological affect.
Claims 16 – 19 are rejected under 35 U.S.C. 103 as being unpatentable over Patent Application Publication US 2019/0358230 A1 to Gmachl et. al. (Gmachl’230; cited on the IDS).
The teachings of Gmachl’230 as they relate to claim 1, from which claims 16 – 19 depend, is given previously in this office action and are fully incorporated here.
However, Gmachl’230 fails to teach a compound of Formula (XII)
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. See claim 16. Additionally, Gmachl’230 fails to teach a compound of Formula (XIII)
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. See claim 17. Moreover, Gmachl’230 fails to teach a compound of Formula (XIV)
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. See claim 18. Furthermore, Gmachl’230 fails to teach a compound of Formula (XV)
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. See claim 19.
Nevertheless, the only difference between the prior art compound species number I-288 of
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and the compounds of the instant application as recited in claims 16 – 19 is the location of the L-RB substituent. Thus the only differences between the instant application and the prior art compound number I-288 is the position of the linker, both the prior art compound number I-288 and the instant application compounds are positional isomers. Hence for position isomers (compounds having the same radicals in physically different positions on the same nucleus) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See MPEP 2144.09(II).
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Patent Application Publication US 2019/0358230 A1 to Gmachl et. al. (Gmachl’230; cited on the IDS) in view of Ali et. al. ((2014) Input of Isosteric and Bioisosteric Approach in Drug Design, J. Chem. Soc. Pak., 36, page 150-169).
The teachings of Gmachl’230 as they relate to claim 1, from which claim 9 depends, is given previously in this office action and are fully incorporated here.
However, Gmachl’230 fails to teach a compound of Formula (XX)
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where instead of a phenyl there is a thiophene ring. See claim 9.
Nevertheless, Ali et. al. teach isosterism or bioisosterism is one of the approaches most frequently used in the design of new molecules. See page 150 column 1 paragraph 1. Furthermore, Ali et. al. teach that bioisosterism is a well-established technique in modern drug design, extensively studied for modification of drug target selectivity, bioactivity, efficacy, potency, membrane permeability, biotransformation pathways and toxicity profile. See page 150 column 1 paragraph 1. Moreover, Ali et. al. teach that the isosteric replacement approach is a practical and, possibly, better substitutes to recent lead optimization techniques. See page 150 column 1 paragraph 1. Specifically, Ali et. al. teach benzene ring equivalents shown below
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. See page 158 Table 7. Thus Ali et. al. suggest
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as known in the prior art ring equivalents to benzene.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to modify prior art compound number I-288 of Gmachl’230 in view of Ali et. al. to use a
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in the R2c position. One of ordinary skill in the art would have been motivated to make this modification to modify a drug target selectivity, bioactivity, efficacy, potency, membrane permeability, biotransformation pathways and toxicity profile. One or ordinary skill in the art would have had a reason expectation of success because benzene ad thiophene are known in the prior art to be ring equivalents.
Claims 29 – 32 are rejected under 35 U.S.C. 103 as being unpatentable over Patent Application Publication US 2019/0358230 A1 to Gmachl et. al. (Gmachl’230; cited on the IDS) in view of Ali et. al. ((2014) Input of Isosteric and Bioisosteric Approach in Drug Design, J. Chem. Soc. Pak., 36, page 150-169).
The teachings of Gmachl’230 and Ali et. al. as they relate to claims 1 and 9, from which claims 29 – 32 depend, are given previously in this office action and are fully incorporated here.
However, Gmachl’230 and Ali et. al. fail to teach a compound of Formula (XXI)
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. See claim 29. Additionally, Gmachl’230 and Ali et. al. fail to teach a compound of Formula (XXII)
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. See claim 30. Moreover, Gmachl’230 and Ali et. al. fail to teach a compound of Formula (XXIII)
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. See claim 31. Furthermore, Gmachl’230 and Ali et. al. fail to teach a compound of Formula (XXIV)
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. See claim 32.
Nevertheless, the only difference between the prior art compound species number I-288 of
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and the compounds of the instant application as recited in claims 29 – 32 is the location of the L-RB substituent. Thus the only differences between the instant application and the prior art compound number I-288 is the position of the linker, both the prior art compound number I-288 and the instant application compounds are positional isomers. Hence for position isomers (compounds having the same radicals in physically different positions on the same nucleus) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See MPEP 2144.09(II).
Claim 105, is rejected under 35 U.S.C. 103 as being unpatentable over Patent Application Publication US 2019/0358230 A1 to Gmachl et. al. (Gmachl’230; cited on the IDS) in view of Troup et. al. ((2020), Current strategies for the design of PROTAC linkers: a critical review, Explor Target Antitumor Ther., 1, 273 – 312).
The teachings of Gmachl’230 as they relate to claim 1, from which claim 105 depends, is given previously in this office action and are fully incorporated here.
However, Gmachl’230 fails to teach a compound where L is selected from a list. See claim 105.
Nevertheless, Troup et. al. teach that proteolysis targeting chimeras (PROTACs) are heterobifunctional molecules consisting of two ligands connected by a linker. See page 274 paragraph 1. Furthermore, Troup et. al. teach that PROTACs act as adapter molecules between the E3 ligase and any chosen POI, hijacking the activity of the cell’s natural protein degradation machinery, i.e. the ubiquitin-proteasome system (UPS).See page 274 paragraph 1. Specifically, Troup et. al. teach that alkyl linker motif represent about 31 % occurrence rate in maple database structures. See page 279 Table 1. Moreover, Troup et. al. teach that by far the most common motifs incorporated into PROTAC linker structures are PEG and alkyl chains of varying lengths, and these are the sole motif in approximately 55% and 30% of linkers respectively. See page 279 paragraph 2. Additionally, Troup et. al. teach key advantages to these compositions that include their synthetic accessibility, their flexibility, and the ability to easily tune their length and composition via a wide array of robust chemical methods. See page 280 paragraph 1. Moreover, Troup et. al. teach that using diverse combinations of PEG and alkyl motifs also allows for tuning of important physical properties such as topological polar surface area (TPSA) and lipophilicity. See page 280 paragraph 1. Now, while Troup et. al. fails to specifically recite L is
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given the relative skill of one of the pharmaceutical arts, such artisan would attempt to optimize the linker length to get either of the instant linkers.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to modify the compound of Gmachl’230 that is to substitute the linker piperidine of compound I-288 in view of Troup et. al. for a –(CH2)7- or –(CH2)8- alkyl chain of claim 105. One of ordinary skill in the art would have been motivated to make this modification due to the modification to easily optimize their length in the pursuit of improved SOS1 inhibitors. One of ordinary skill in the art would have had a reasonable expectation of success because alkyl linkers are one of the most common motifs used as linkers.
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 1, 4, 9, 11 – 13, 15 – 19, 24, 95, and 105, are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 23 of U.S. Patent No. US 12419962 B2 to Erdman et. al. (Erdman‘962).
Claims 107, and 112 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 23 of U.S. Patent No. US 12419962 B2 to Erdman et. al. (Erdman‘962) in view of Patent Application Publication US 2019/0358230 A1 to Gmachl et. al. (Gmachl’230; cited on the IDS), Patani et. al. ((1996), Bioisosterism A rational approach in drug design, Chem. Rev., 96, 3147-3176), Troup et. al. ((2020), Current strategies for the design of PROTAC linkers: a critical review, Explor Target Antitumor Ther., 1, 273 – 312), and Ali et. al. ((2014) Input of Isosteric and Bioisosteric Approach in Drug Design, J. Chem. Soc. Pak., 36, page 150-169).
Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant application and the invention of Erdman‘962 direct to a compound of Formula (I)
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or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. See reference claims 1, 4, and 5. See instant claims 1, 4, 9, 11 – 13, 24, 95, 105.
In regards to the instant dependent claims wherein the L-RE feature is attached at different positions of the ring as recited in instant claims 16 – 19 and 29 – 32; given that that only difference between the instant compounds and the compounds of Erdman‘962 is the position of the L-RE feature the compounds of both the instant application and copending Erdman‘962 are positional isomers. Therefore compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977)(MPEP 2144.09(II)).
However, Erdman‘962 fail to recite a composition comprising a compound of instant claim 1 and a pharmaceutically acceptable excipient. See instant claim 107. Additionally, Erdman‘962 fail to recite a method of treating, preventing, or ameliorating one or more symptoms of a disorder, disease, or condition mediated by a son of sevenless homolog 1 (SOS1) in a subject, comprising administering a compound of instant claim 1. See instant claim 112.
The teachings of Gmachl’230, Patani et. al., Troup et. al., and Ali et. al. as they relate to the prior art rejections of instant claims 1, 4, 9, 11 – 13, 15 – 19, 29 – 32, 95, 105, 107, and 112, are given previously in this office action and are fully incorporated here.
Therefore it would have been obvious before the effective filing date of the instant application to modify the invention of Erdman‘962 to use the compounds in view of Gmachl’230, that is in a pharmaceutical composition for use in treating, preventing, or ameliorating one or more symptoms of a disorder, disease, or condition mediated by a son of sevenless homolog 1 (SOS1) in view of Ali et. al. to use a
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in the R2c position, in view of Patani et. al. that is to have a trivalent ring substitution of instant V from -CH= to -N= in further view of Troup et. al. for a –(CH2)7- or –(CH2)8- alkyl chain of claim 105.
One of ordinary skill in the art would have been motivated to make this modification to modify a drug target selectivity, bioactivity, efficacy, potency, membrane permeability, biotransformation pathways and toxicity profile. One or ordinary skill in the art would have had a reason expectation of success because benzene ad thiophene are known in the prior art to be ring equivalents. One of ordinary skill in the art would have been motivated to make this modification to rationally modify compound number I-288 safer and more clinically effective agent. One of ordinary skill in the art would have had a reasonable expectation of success because the trivalent substitution of -CH= with -N= is commonly used in modern drug design. Moreover, in the prior art example where a trivalent ring substitution of -CH= with -N= in the antibacterial agent the bioisostere was also exhibited favorable biological affect. One of ordinary skill in the art would have been motivated to make this modification due to the modification to easily optimize their length in the pursuit of improved SOS1 inhibitors. One of ordinary skill in the art would have had a reasonable expectation of success because alkyl linkers are one of the most common motifs used as linkers.
Claims 1, 4, 9, 11 – 13, 15 – 19, 29 – 32, 95, 105, 107, and 112 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 8 – 11, 22 – 23, 40 – 45, 50 – 53, 66 – 69, 140, and 145 of copending Application No. 18/542628 to Chan et. al. (Chan’628).
Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant application and the invention of Chan’628 direct to a compound of Formula (I)
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or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. See reference claims 1, 8 – 11, 22 – 23, 40 – 45, 50 – 53. See instant claims 1, 4, 9, 11 – 13, 24, 95, and 105. Moreover, Chan’628 recite a composition comprising a compound of reference claim 1 and a pharmaceutically acceptable excipient. See reference claim 140. See instant claim 107. Additionally, Chan’628 recite a method of treating, preventing, or ameliorating one or more symptoms of a disorder, disease, or condition mediated by a son of sevenless homolog 1 (SOS1) in a subject, comprising administering a compound of reference claim 1. See reference claim 145. See instant claim 112.
In regards to the instant dependent claims wherein the L-RE feature is attached at different positions of the ring as recited in instant claims 16 – 19 and 29 – 32; given that that only difference between the instant compounds and the compounds of Chan’628 is the position of the L-RE feature the compounds of both the instant application and copending Chan’628 are positional isomers. Therefore compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977)(MPEP 2144.09(II)).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 4, 9, 11 – 13, 15 – 19, 29 – 32, 95, 105, 107, and 112 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 8 – 13, 22 – 24, 34 – 35, 76 – 92, 129, 139, 141, and 146 - 147 of copending Application No. 18/245125 to Chourasia et. al. ( Chourasia’125).
Chourasia’125 recite a compound of Formula (II)
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or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. See reference claims 1, 8 – 11, 22 – 23, 40 – 45, 50 – 53. See instant claims 1, 8 – 10, 12, 23, 78 – 79, and 140. Moreover, Chourasia’125 recite a compound where reference R4 is -L-RB where reference RB that is instant RE, is C2-6 fluoroalkyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl. See reference claim 1.
Moreover, Chourasia’125 recite a composition comprising a compound of reference claim 1 and a pharmaceutically acceptable excipient. See reference claim 141. See instant claim 107. Additionally, Chourasia’125 recite a method of treating, preventing, or ameliorating one or more symptoms of a disorder, disease, or condition mediated by a son of sevenless homolog 1 (SOS1) in a subject, comprising administering a compound of reference claim 1. See reference claims 146 - 147. See instant claim 112.
In regards to the instant dependent claims wherein the L-RE feature is attached at different positions of the ring as recited in instant claims 16 – 19 and 29 – 32; given that that only difference between the instant compounds and the compounds of Chourasia’125 is the position of the L-RE feature the compounds of both the instant application and copending Chourasia’125 are positional isomers. Therefore compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977)(MPEP 2144.09(II)).
This is a provisional nonstatutory double patenting rejection.
Claims 1, 4, 9, 11 – 13, 15 – 19, 29 – 32, 95, 105, 107, and 112 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 – 3, 29, 31 – 32, 35, 45 – 47, 59, 63 – 64, 77, 82 – 85, 163, 171, and 176 of copending Application No. 18/847237 to Erdman et. al. ( Erdman’237).
Erdman’237 recite a compound of Formula (I)
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or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. See reference claims 1 – 3, 29, 31 – 32, 35, 45 – 47, 59, 63 – 64, 77, 82 – 85, and 163. See instant claims 1, 8 – 10, 12, 23, 78 – 79, and 140.
Moreover, Erdman’237 recite a composition comprising a compound of reference claim 1 and a pharmaceutically acceptable excipient. See reference claim 171. See instant claim 107. Additionally, Erdman’237 recite a method of treating, preventing, or ameliorating one or more symptoms of a disorder, disease, or condition mediated by a son of sevenless homolog 1 (SOS1) in a subject, comprising administering a compound of reference claim 1. See reference claim 176. See instant claim 112.
In regards to the instant dependent claims wherein the L-RE feature is attached at different positions of the ring as recited in instant claims 16 – 19 and 29 – 32; given that that only difference between the instant compounds and the compounds of Erdman’237 is the position of the L-RE feature the compounds of both the instant application and copending Erdman’237 are positional isomers. Therefore compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977)(MPEP 2144.09(II)).
This is a provisional nonstatutory double patenting rejection.
Claims 1, 4, 9, 11 – 13, 15 – 19, 29 – 32, 95, 105 – 107, and 112 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 153, 156, and 161 – 162 of copending Application No. 19/510087 to Okano et.al. (Okano’087).
Okano’087 recite a compound of Formula (I)
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or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. See reference claims 1 – 153. See instant claims 1, 8 – 10, 12, 23, 78 – 79, and 140.
Moreover, Okano’087 recite a composition comprising a compound of reference claim 1 and a pharmaceutically acceptable excipient. See reference claim 156. See instant claim 107. Additionally, Okano’087 recite a method of treating, preventing, or ameliorating one or more symptoms of a disorder, disease, or condition mediated by a son of sevenless homolog 1 (SOS1) in a subject, comprising administering a compound of reference claim 1. See reference claims 161 – 162. See instant claim 112.
In regards to the instant dependent claims wherein the L-RE feature is attached at different positions of the ring as recited in instant claims 16 – 19 and 29 – 32; given that that only difference between the instant compounds and the compounds of Okano’087 is the position of the L-RE feature the compounds of both the instant application and copending Okano’087 are positional isomers. Therefore compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977)(MPEP 2144.09(II)).
This is a provisional nonstatutory double patenting rejection.
Discussion of the prior art
Claim 106 directs to a compound selected from a list of compounds.
The closet prior art of Patent Application Publication US 2019/0358230 A1 to Gmachl et. al. (Gmachl’230; cited on the IDS) teach new benzylamino substituted quinazolines and derivatives of formula (I)
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and their use as inhibitors of SOS1. See page 1 paragraph 0001. Specifically, Gmachl’230 teach compound number I-288 of
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where instant V = -C(R4)= and instant R4 = -L-RB where instant L = piperidine and instant RB = isopropyl; instant U = X = Y = -C(R5)= where instant R5 = H and CH3; instant R1 = CH3; instant R3 = H; instant R2a = H; instant R2b = CH3; and instant R2c = m-CH3-Phenyl. See page 159 Table 47 Row 1. Moreover, Gmachl’230 teach compound number I-288 has an IC50 against SOS1 of 22 nM. See page 159 Table 47 Row 1.
However, Gmachl’230 does not teach any of the recited compounds in claim 106. Moreover the prior art fails to provide a motivation for modifying the prior art compound number I-288 to render obvious the compounds of claim 106. Since the prior art fails to anticipate or render obvious the compounds of claim 106; claim 106 is free of the prior art.
Conclusion
Claims 1, 4, 9, 11 – 13, 15 – 19, 29 – 32, 95, 105 – 107, and 112 are rejected.
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/DAWANNA SHAR-DAY WHITE/Examiner, Art Unit 1627
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