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 .
DETAILED ACTION
Claims 1-3, 7-8, 14-16, 18-21, 23, 28-29, 33-35 and 40-41 are pending in the present application file.
Election/Restrictions
Applicant’s election of Group I (claims 1-3, 7-8, 14-16, 18-21, 23, 28-29, 32-33 and 40-41; directed to a compound of formula (I), or a pharmaceutically acceptable salt, an enantiomer, a diastereomer, a racemate, a solvate, a hydrate, a polymorph, a prodrug or an isotopic variant thereof, and a mixture thereof) and a species of present formula (I) with traverse in the reply filed April 21, 2026 is acknowledged.
The traversal over the groups of invention is on grounds the Groups I-III relate to a single general inventive concept and should be considered to have unity of invention, the requirement depends on a reference which the present compounds having a patently distinct common core structure and common activity. The election of species traversal is on grounds the search and examination of the entire application could be made without serious burden.
The Examiner has considered the traversal fully but must disagree for the following reasons.
Although the present application contains claims to a product and method of using, thus having unity of invention under PCT guidelines, the present claims do not have a shared special technical feature that makes a contribution over the prior art as discussed in the rejections under 35 U.S.C. 102 and 35 USC 103 below.
The requirement is still deemed proper and is therefore made FINAL.
As per MPEP 803.02, the examiner will determine whether the entire scope of the claims is patentable. Applicants' elected species of present formula (I) appears free of the prior art. Therefore, according to MPEP 803.02: should the elected species be found allowable, the examination of the Markush-type claim will be extended. If the examination is extended and a non-elected species found not allowable, the Markush-type claim shall be rejected and claims to the nonelected invention held withdrawn from further consideration. The examination of the Markush-type claims has been extended to include the species cited below under 35 U.S.C. 102 and 103, which are not allowable.
As a non-elected species has been found not allowable, the Markush-type claims have been rejected and claims to the nonelected invention held withdrawn from further consideration. Claims 1-3, 7-8, 14-16, 18, 20, 28-29, 33 and 41 have been examined to the extent that they embrace and are readable on the elected embodiment and the above identified nonelected species. Since the nonelected species has been found not allowable, subject matter not embraced by the elected embodiment or the above identified nonelected species is therefore withdrawn from further consideration.
Claims 19, 23, 32, 34-35 and 40 do not read on the presently searched and examined subject matter. Therefore, claims 19, 23, 32, 34-35 and 40 are withdrawn from consideration by the Examiner under 37 CFR 1.142(b) as being drawn to a non-elected invention.
Priority
The following continuity data is acknowledged in the present application file:
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Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The Information Disclosure Statement(s) filed 03/21/2024, 04/28/2025 and 04/23/2026 have been acknowledged by the Examiner. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the Examiner.
Specification
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
In chemical patent abstracts for compounds or compositions, the general nature of the compound or composition should be given as well as its use, e.g., “The compounds are of the class of alkyl benzene sulfonyl ureas, useful as oral anti-diabetics.” Exemplification of a species could be illustrative of members of the class. For processes, the type of reaction, reagents and process conditions should be stated, generally illustrated by a single example unless variations are necessary.
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because the language should be clear and concise and should not repeat information given in the title, the abstract should avoid using phrases which can be implied, and the general nature of the compound or composition should be given as well as its use, e.g., “The compounds are of the class of alkyl benzene sulfonyl ureas, useful as oral anti-diabetics.”
A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3, 7-8, 15-16, 18, 29, and 33 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO 2022194269 (Pan et al.; Priority to CN 2021-10295835 A, Published: 03/19/2021).
Pan discloses bifunctional compound of formula (I) capable of degrading an EGFR, a pharmaceutical composition containing the compound, a preparation method, and a method for treating a cell proliferative disease, such as a cancer, by using the compound. See abstract.
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409
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See last line, second compound of page 36 for a specific compound example of Pan (Pan-1) which corresponds to a compound of present formula (I) wherein:
PIN represents formula (Ia)
Q is P(O)Rq1Rq2
Rq1 and Rq2 are each independently selected from -C1 alkylene-Rqn
Rqn is hydrogen
J1 is CRJ1, J2 is CRJ2, J3 is CRJ3 and J4 is CRJ4
RJ1, RJ2, RJ3, and RJ4 are each independently hydrogen
V1 is N, V2 is N, V3 is CR3 and V4 is CR4
R3 is hydrogen
R4 is halogen (fluorine)
K1 is CRk1, K2 is CRk2 and K4 is CRk4
Rk1 is hydrogen
Rk2 is C1 alkoxy
Rk4 is hydrogen
Rk3 is
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89
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Ra is methyl
Rb is hydrogen
L5 and L6 are each independently NR00
R00 is H
Ring A is 6-membered monocyclic heterocyclylene; the heteroatom is N and the number of the heteroatom is 2
R is 6-membered monocyclic heterocyclylene; the heteroatom is N and the number of the heteroatom is 1
Linker represents
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44
111
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L1 is (CR21R22)n3
R21 and R22 are each independently hydrogen
n3 is 2
L2 is (CR21R22)n3
R21 and R22 are each independently hydrogen
n3 is 1
L3 is a bond
L4 is (CR21R22)n3
R21 and R22 are each independently hydrogen
n3 is 2
E represents
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151
120
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W is NR00
R00 is hydrogen
Z1 is N and Z2 is C(O)
G1 is CRG1, G2 is CRG2, G3 is CRG3 and G4 is CRG4
RG1 is attached to W
RG2, RG3 and RG4 are each independently selected from hydrogen.
Compound Pan-1 is encompassed by present claim 2 where
A is ring A-2,
Y1 and Y2 are N,
t5 is 1 and t6 is 2
R is R-4
Y7 is N and Y8 is CH
s5 is 1 and s6 is 2.
Compound Pan-1 is also encompassed by present claims 3, 7-8, 15-16, 18, and 29.
Pan discloses a pharmaceutical composition comprising a therapeutically effective amount of the above-mentioned bifunctional compound or its stereoisomer, tautomer, pharmaceutically acceptable salt, prodrug, hydrate, solvate, isotopically labeled derivatives and pharmaceutically acceptable carriers, where pharmaceutically acceptable carriers includes adjuvants or excipients. See page 38 of Pan. Pan provides where excipients of the invention may include diluents, preservatives, fillers, flow regulators, disintegrants, wetting agents, emulsifiers, suspending agents, sweeteners, flavoring agents, perfuming agents, antibacterial agents, antifungal agents, lubricants agent and dispersants. See present claim 33.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-3, 7-8, 14, 16, 18, 20-21 and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Ren (Ren, Chaowei, et al. "Discovery of a brigatinib degrader SIAIS164018 with destroying metastasis-related oncoproteins and a reshuffling kinome profile." Journal of Medicinal Chemistry 64.13 (2021): 9152-9165.).
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Ren discloses Brigatinib-based degraders as well as the successful synthesis and evaluation of the degrader SIAIS164018. Ren discloses SIAIS164018 as compound 6. See Table 1 on page 9154.
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SIAIS164018 of Ren corresponds to a compound of present formula (I) wherein:
PIN represents formula (Ia)
Q is P(O)Rq1Rq2
Rq1 and Rq2 are each independently selected from -C1 alkylene-Rqn
Rqn is hydrogen
J1 is CRJ1, J2 is CRJ2, J3 is CRJ3 and J4 is CRJ4
RJ1, RJ2, RJ3, and RJ4 are each independently hydrogen
V1 is N, V2 is N, V3 is CR3 and V4 is CR4
R3 is hydrogen
R4 is halogen (chlorine)
K1 is CRk1, K2 is CRk2 and K4 is CRk4
Rk1 is hydrogen
Rk2 is C1 alkoxy
Rk4 is hydrogen
Rk3 is hydrogen
L5 and L6 are each independently NR00
R00 is H
Ring A is 6-membered monocyclic heterocyclylene; the heteroatom is N and the number of the heteroatom is 1
R is 6-membered monocyclic heterocyclylene; the heteroatom is N and the number of the heteroatom is 2
Linker represents
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44
111
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L1 is C(O)
L2 is (CR21R22)n3
R21 and R22 are each independently hydrogen
n3 is 1
L3 is a bond
L4 is (CR21R22)n3
R21 and R22 are each independently hydrogen
n3 is 0
E represents
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151
120
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W is NR00
R00 is hydrogen
Z1 is N and Z2 is C(O)
G1 is CRG1, G2 is CRG2, G3 is CRG3 and G4 is CRG4
RG1 is attached to W
RG2, RG3 and RG4 are each independently selected from hydrogen.
Compound SIAIS164018 is encompassed by present claim 2 where
A is ring A-2,
Y1 is N and Y2 is CH,
t5 is 1 and t6 is 2
R is R-4
Y7 and Y8 are N
s5 is 1 and s6 is 2.
Compound SIAIS164018 is also encompassed by present claims 3, 7-8, 14, 16, 18 and 20-21 (encompassed by present formula (III-1-1)).
Regarding the ALK and EGFR degradation activity of SIAIS164018, Ren discloses the following on page 9158:
Degradation of mutant ALK (G1202R) or EGFR (L858R + T790M) had been achieved by SIAIS164018. From other biological phenotypes, SIAIS164018 induced G1 cell cycle arrest distinguishing from Brigatinib in lung cancer cell Calu-1 and triple negative breast cancer MDA-MB-231; inhibition of cell migration and invasion were also achieved post-treating SIAIS164018 in both metastatic Calu-1 and MDA-MB-231 cell lines.
Regarding present claim 33, Ren discloses an in vitro metabolism assay including the preparation of compound stock solutions, where the compound SIAIS164018 is in DMSO, which is a pharmaceutically acceptable excipient. See page 9162.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
The difference between the instant claims and the prior art compound example compound SIAIS164018is that the instant claims replaces one H of the prior art compound with a methyl at the Rk3 position.
Finding of prima facie obviousness --- rationale and motivation (See
MPEP § 2142-2143)
It is well established that the substitution of methyl for hydrogen on a known compound is not a patentable modification absent unexpected or unobvious results. In re Wood, 199 USPQ 137 (CCPA 1978) and In re Lohr, 137 USPQ 548, 549 (CCPA 1963). The motivation to make the claimed compounds derives from the expectation that structurally similar compounds would possess similar activity.
Ren teaches a compound of present formula I where Rk3 = C0 alkyl. Substitution of Rk3 = C0 alkyl of Ren for where Rk3 = C1 alkyl of the present invention is presumed to be an obvious variant. One of ordinary skill would expect a compound of Ren where Rk3 = C1 alkyl to have similar biological properties and activity – inhibiting ALK or EGFR as well as the prevention or treatment of a tumor or disease states dependent on ALK or EGFR – of compounds of the present invention. There would be a reasonable expectation of success that the structurally similar compound SIAIS164018 of Ren would possess similar activity to a compound of the present invention.
Therefore, the compound of Ren is presumed to be an obvious variant of the present compound of structural formula I and the present claims are prima facie obvious.
Allowable Subject Matter
Claims 23, 28, and 41 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Claims 19, 23, 34-35 and 40 are withdrawn.
Claims 1-3, 7-8, 14-16, 18, 20-21, 29, and 33 are rejected.
Claims 23, 28, and 41 are objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to QUINCY A MCKOY whose telephone number is (703)756-4598. The examiner can normally be reached Monday - Thursday 8:00 - 6:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Murray can be reached at 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/QUINCY A. MCKOY/
Patent Examiner, Art Unit 1626
/KAMAL A SAEED/Primary Examiner, Art Unit 1626
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