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 .
Election/Restrictions
Applicant’s election with traverse of Group I, encompassed by claims 1-10 and 12, drawn to a compound and pharmaceutical composition of Formula (I), in the reply filed on 6/22/2026 is acknowledged. The traversal is on the ground(s) that:
Groups I-III represent, and are related to each other as, a single inventive concept, where a search for compounds or compositions as delineated in claim 1 would also function to search for art pertaining to methods of their use;
Product and process of use claims are permitted to be examined together in one application, according to 37 CFR 1.475(b)(2);
R3 of instant claim 1 is defined by variables that are not allowed by the prior art teaching cited by Examiner (WO 2020/057511), which requires a heteroatom-linked nitrogen-containing bicyclic ring system at R3.
Applicant’s argument that product and process of use claims are permitted to be examined together in one application, according to 37 CFR 1.475(b)(2), is not found persuasive. 37 CFR 1.475(b)(2) is drawn to “a product and a process of use of said product” (emphasis added). Presently, instant claims are drawn to a product and at least two processes of use, which is more than a process.
Examiner acknowledges the distinction in the genus of instant Formula (I) (e.g. R3) compared to the genus of reference art. However, Examiner maintains the restriction requirement because the special technical feature of Group (I) can be found in Tang et al. (US 8,901,140 B2, published 12/2/2014)(hereinafter, ‘Tang’). A forthcoming discussion explaining why Groups I-III do not relate to a single general inventive concept under PCT Rule 13.1 is provided in the 35 USC § 103 Rejection Section of this Office Action.
Because a different prior art reference is being applied herein, Applicant can still traverse the restriction requirement, and the requirement is therefore NOT FINAL.
Applicant has elected with traverse the following species, Compound of Example 1:
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Applicant asserts that claims 1-10, and 12 read upon the provisionally elected species. Therefore, claims 1-15 are pending and claims 1-10, and 12 are presently under examination. Claims 11, and 13-15 are withdrawn based on the species election and restriction requirement.
Priority
The instant application is application is a 35 U.S.C. § 371 International PCT Application No. PCT/CN2022/122577, filed September 29, 2022, which claims the priority of CN202111158182.1, filed September 30, 2021.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 07/09/2024 is in compliance with the provisions of 37 CFR 1.97. All references have been considered except where marked with a strikethrough. A signed copy of Form 1449 is included with this Office Action.
Examiner puts on the record that the foreign references disclosed as “104119350” and “1764651” were joined as one foreign document in the file wrapper, rather than two discrete documents. Furthermore, the document of CN1764651A is not complete. It ends abruptly at page 147, and CN104119350A begins. Therefore, CN1764651A has not been considered.
Claim Objections
Claims 1-8, and 12 are objected to for the same following informality: the preamble to the claim should be bridged with the word “or” between “a stereoisomer thereof,” and “a pharmaceutically acceptable salt thereof”, as it properly does in claim 9, instead of with the word “and”. Appropriate correction is required.
Claim 1 is objected to because of the following informalities:
The word “wherein” should be inserted before “in formula (I)…” in the preamble of the claim;
The word “wherein” should be inserted before the recitation of both “Ra and Rb are each independently hydrogen…” and “the 4- to 7-membered heteroalicyclyl group is…” to indicate that Ra, Rb, and the 4- to 7-membered heteroalicyclic group are referring back to the previously recited Ra, Rb, and the 4- to 7-membered heteroalicyclic group in R1;
In the limitation of R2, the word “which” should be amended to recite “wherein C1-C6 alkyl…” for clarity;
For clarity, in the limitation of R1, the phrase “1-2 substituents” should be replaced with “1 or 2 substituents”;
The word “and” should appear after the claim limitation of R2 in order to bridge to the limitation of R3, R4, and R5 so as to be consistent with proper Markush practice.
Claim 2 is objected to because of the following informalities:
In the limitation of m, the comma should be replaced with a semicolon so as to read “m is 0 or 1;”
The word “wherein” should be inserted before the recitation of both “Ra and Rb are each independently hydrogen…” and “the 4- to 7-membered heteroalicyclyl group is…” to indicate that Ra, Rb, and the 4- to 7-membered heteroalicyclic group are referring back to the previously recited Ra, Rb, and the 4- to 7-membered heteroalicyclic group in R1;
The limitation of Ra and Rb should end with a comma, as in the previous claim 1, and not a semicolon, so as to read “…or C1-C3 alkoxy-substituted C1-C3 alkyl,”.
In the limitation of the 4- to 7-membered heteroalicycyl group, the word “hydroxy” should be replaced with “hydroxyl” so as to be consistent with the previous language of claim 1.
Claim Rejections - 35 USC § 112(b)
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.
Claims 2 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 2 recites the limitation "the above groups” in the limitation of 4- to 7-membered heteroalicyclyl group. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 2 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 2 recites that the 4- to 7-membered heteroalicyclyl can be substituted with aldehyde. This expands the scope of claim 1, from which claim 2 depends. Claim 1 does recite that the 4- to 7-membered heteroalicyclyl can be substituted with C1-C4 acyl. An acyl group is of general format R-C(O), where R is an alkyl, aryl, hydrogen, etc. The C1 acyl group is an acyl group where R = CH3, so as to form the simplest acyl group—the acetyl. The term aldehyde is not covered by C1-C4 acyl. Thus, claim 2 broadens the scope of claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
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.
Claim(s) 1-7, 9-10, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Tang et al. (US 8,901,140 B2, published 12/2/2014)(hereinafter, ‘Tang’).
The instant application claims compounds of Formula (I) that are alternatively usable, wherein R3 = F, R4 = Cl, R5 = H, R2 = ethyl, m = 0, and R1 = 1-methylpyrrolidin-2-yl, with the -OR2 substituent at the C-5 position of the quinazoline, shown encircled below, for use as an EGFR or HER2 inhibitor.
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The instant application also claims the method of preparing compounds of instant Formula (I) and a pharmaceutical composition thereof.
Tang teaches (cols 52-54) Example 9, with the oxygen-bearing substituent connected to the quinazoline at the C-7 position, shown encircled below, for use as an EGFR or HER2 inhibitor.
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Tang teaches the synthesis of preparing reference Example 9 (cols 53-54), its potency in an EGFR cell proliferation inhibition assay and in an EGFR kinase activity assay (cols 57-58), and a pharmaceutical composition thereof (claim 12). Tang also teaches co-administration of reference invention with other antitumor drugs (col 15, lines 1-10).
It can be seen that the species taught by Tang is a positional isomer of compounds of instant claims where the connection of the OR2 group to the quinazoline is shifted. These compounds are positional isomers and considered equivalent. The MPEP 2144.09 states “Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. Adjacent homologues are generally so structurally similar that "without more" such structural similarity could give rise to prima facie obviousness. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). MPEP 2144.08(II)(A)(4)(c).
Here, the prior art teaches a highly similar structural isomer of the instantly claimed invention, wherein such isomers have the same utility as the instantly claimed compounds. Therefore, the close structural similarity between the compounds of Tang and compounds of instant claims 1-7, 9-10, and 12 renders the instant claims 1-7, 9-10, and 12 obvious because one of ordinary skill in the art would readily appreciate that isomers of such compounds could be utilized for the use in EGFR or HER2 inhibition, as taught by the prior art.
One of ordinary skill would have a reasonable expectation of success in synthesizing a positional isomer of the compound taught by Tang since it is well known in the art that positional isomers have similar chemical properties. It would be expected that altering a known compound by creating a positional isomer would result in a compound with the same chemical properties and utility as the known compound.
Thus, said claims are rendered obvious.
Claim(s) 1-10, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (WO 2011/084796 A2, published 07/14/2011)(hereinafter, ‘Zhang).
The instant application claims compounds of Formula (I) that are alternatively usable, wherein R3 = H, R4 = Cl, R5 = F, R2 = methyl, m = 1, R1 = NRaRb, and Ra and Rb = methyl, with the -OR2 substituent at the C-5 position of the quinazoline, shown encircled below, for use as an EGFR or HER2 inhibitor.
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The instant application also claims the method of preparing compounds of instant Formula (I) and a pharmaceutical composition thereof.
Zhang teaches (claim 31, page 90, lines 27-28), the compound (E)-N-(4-(3-chloro-2-fluoro-phenyl-(N-D)-amino)-7-methoxyquinazolin-6-yl)-4-(dimethylamino)but-2-enamide, with the oxygen-bearing substituent connected to the quinazoline at the C-7 position and a deuterated proton on the aniline nitrogen, both shown encircled below, for use as an EGFR or HER2 inhibitor.
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Zhang teaches the general synthesis of preparing the above compound (page 53, Scheme 3), a pharmaceutical composition thereof (claim 32), and co-administration of reference invention with a second therapeutic agent (claims 33-34).
Zhang also teaches that the Rx of the reference genus, shown below, is alternatively usable with H or D (page 5, line 1; claim 1) in order to arrive at instantly claimed compounds. Furthermore, Zhang teaches species where Rx is H (Example 3, page 58), also shown below.
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As discussed in the previous 103 rejection, the compounds of the reference prior art and instant application are positional isomers and considered equivalent. The MPEP 2144.09 states “Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. Adjacent homologues are generally so structurally similar that "without more" such structural similarity could give rise to prima facie obviousness. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). MPEP 2144.08(II)(A)(4)(c).
Regarding deuteration: Moreover, given that there is always a need to enhance the pharmacological effects of a compound (e.g. increased in vivo half-life) without significantly altering its basic chemical structure (first branch), or that there is always a need to reduce the time, cost, risk, and statistical imprecision of pharmacokinetic studies (e.g. measure bioavailability or identify metabolites) (second branch), and that there is only a limited number of ways that this can be done, it would be obvious to pursue a potential solution that has a reasonable expectation of success. See e.g. KSR International Co. v. Teleflex Inc., 1385, 1397; Pfizer, Inc. v. Apotex, Inc., 82 USPQ2d 1321; Alza Corp. v. Mylan Laboratories, Inc., 80 USPQ2d 1001; In re Kubin, 90 USPQ2d 1417; In re O’Farrell, 7 USPQ2d 1673, 1681; In re Eli Lilly & Co., 14 USPQ2d 1741; In re Ball Corp., 18 USPQ2d 1491.
In addition, it is clear under both branches that deuteration per se is a known improvement technique for getting a more useful version of the pharmaceutical, and that the improvement is of a predictable nature, as is seen by the success reported in the various secondary references. Thus, it would have been obvious to one of ordinary skill in the pharmaceutical art to have applied this known improvement technique in the same way to the compound of the primary reference to obtain the results reasonably predictable from the secondary references. See e.g. KSR International Co. v. Teleflex Inc., 1385, 1396; Ruiz v. AB Chance Co., 69 USPQ2d 1686; In re Nilssen, 7 USPQ2d 1500.
Thus, said claims are rendered obvious.
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 1-2, 4-10, and 12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 6-12, and 15-18 of U.S. Patent No. 8,735,409 B2. Although the claims at issue are not identical, they are not patentably distinct from each other.
For example, claim 1 of instant application specifies the limitation where R3, R4, R5 = hydrogen or halogen, R2 = C1 alkyl, m = 1, R1 = NRaRb, where Ra, Rb = C1 alkyl. In these instances, independent claim 1 of instant and reference application cover overlapping scope. Each and every required element of the instant genus of Formula (I) is taught by reference claim 1. Furthermore, reference application teaches a pharmaceutical composition comprising reference compounds (reference claim 15), and a composition further comprising a second agent (e.g. tyrosine kinase inhibitor)(reference claims 16-17).
The instant application teaches the OR2 substitution at C-5 of the quinazoline, but does not teach OR2 substitution at the C-7 position of the quinazoline. However, the positional isomer argument used in the first 103 rejection (“unpatentable over Tang et al.”) is likewise valid and employed herein.
Here, the prior art teaches a highly similar structural isomer of the instantly claimed invention, wherein such isomers have the same utility as the instantly claimed compounds. Therefore, the close structural similarity between the compounds of Zhang and compounds of instant claims 1-2, 4-10, and 12 renders the instant claims 1-2, 4-10, and 12 obvious because one of ordinary skill in the art would readily appreciate that isomers of such compounds could be utilized for the use in EGFR or HER2 inhibition, as taught by the prior art.
One of ordinary skill would have a reasonable expectation of success in synthesizing a positional isomer of the compound taught by Zhang since it is well known in the art that positional isomers have similar chemical properties. It would be expected that altering a known compound by creating a positional isomer would result in a compound with the same chemical properties and utility as the known compound.
Conclusion
All claims are rejected.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LUKE ALAN BORALSKY whose telephone number is (571)272-9746. The examiner can normally be reached Monday - Friday 7:30 am - 5:00 am.
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/L.A.B./Examiner, Art Unit 1624
/SUSANNA MOORE/Primary Examiner, Art Unit 1624
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