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
The preliminary amendment filed 10/14/2024, amended claims 5, 9, 25, 28, 32, 37, 39, cancelled claims 6-7, 10-23, 29-30, 33-35, 38, 40-42, and added claims 43-46.
Claims 1-5, 8-9, 24-25, 27-28, 31-32, 36-37, 39 and 43-46 are pending and examined on the merits herein.
Priority
This application claims the following priority:
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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 39 and 45-46 are 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.
Regarding claim 39, 45, and 46, the phrases "such as" and particularly renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
In view of compact prosecution, for the purpose of applying prior art, the limitations following “such as” and “particularly” are interpreted as exemplary and as not further limiting the claim.
Moreover, since the recitations following “such as” and “particularly” are interpreted as not further limiting the claim, “i),” “ii),” and “iii),” are all interpreted as “wherein the disease is an EGFR kinase-mediated disease.” As such, “ii),” and “iii)” are superfluous and should be deleted.
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.
Claims 3, 9, and 31-32 are 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 3 depends from claim 2, wherein claim 2 defines its compound (X) as:
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. However claim 3 recites a -N(Rs)S(O)2(CH3) group at the -P(O)(CH3)2 group of compound (I) of claim 2. Claim 31, which depends from claim 3, also recites a -N(Rs)S(O)2(CH3) group at the -P(O)(CH3)2 group of compound (I) of claim 2.
-Claim 9 depends from claim 8, wherein claim 8 defines “n” as 1, 2, 3, or 4. However, claim 9, in wherein “iv),” defines n as 1, 2, 3, 4, or 5.
-Claim 31 depends ultimately from claim 2, wherein claim 2 defines R6 as
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, and claim 31 broadens the scope of the definition of R6 by defining it as
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.
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 § 112(a)-Scope of Enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-5, 8-9, 24-25, 27-28, 31-32, 36-37, 39 and 43-46 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a) compounds of formula (A), (X), and the species of claim 36, and pharmaceutically acceptable salts thereof of claims 1-5, 8-9, 24-25, 27-28, 31-32, 36, and 43-44 and b) a method of treating an EGFR kinase mediate disease by administering a compound of formula (A) or (X), and pharmaceutically acceptable salts thereof, it does not reasonably provide enablement for a) enantiomers, diastereomers, racemates, solvates, hydrates, polymorphs, prodrugs, or isotropic variants of compounds of formula (A), (X), or the species of claim 36 or b) a method of preventing an EGFR kinase mediated disease by administering a compound formula (A), (X), or the species of claim 36, or pharmaceutically acceptable salts, enantiomers, diastereomers, racemates, solvates, hydrates, polymorphs, prodrugs, or isotropic variants thereof.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The criteria for enablement set out in the In re Wands, MPEP 2164.01(a), considers the following factors:
Breadth of the Claims
Independent claims 1, 2 and 36 are directed toward any pharmaceutically acceptable salts, enantiomers, diastereomers, racemates, solvates, hydrates, polymorphs, prodrugs, or isotropic variants of instant compounds (A), (X), and the species of claim 36.
Claims 39, and 45-46 are directed toward a method of treating or preventing any EGFR kinase mediated disease with any pharmaceutically acceptable salts, enantiomers, diastereomers, racemates, solvates, hydrates, polymorphs, prodrugs, or isotropic variants of instant compounds (A), (X), and the species of claim 36.
As such, the breadth of the claims is great.
Level of Skill in Art
The level of skill in the art is a clinician or an artisan with a PhD.
State of the Prior Art
As detailed in the below prior art rejections WO 2021/036922 to Zhao teaches the instantly claimed compounds and teaches methods of treating EGFR kinase mediated diseases with the recited compounds. However, Zhao exemplifies zero methods of treating or preventing EGFR kinase mediated diseases, but merely provides IC50 (nM) inhibitory values for EGFR receptors (pgs. 126-128, 130-131, Original). Moreover, Zhao does not exemplify its compounds as pharmaceutically acceptable salts, enantiomers, diastereomers, racemates, solvates, hydrates, polymorphs, prodrugs, or isotropic variants.
Similarly, while WO 2022/171123 to Liu (published 02/09/2022, IDS of 12/11/2025) teaches a method of treating EGFR diseases by administering structurally similar compounds (claims 39, 42-46, pgs. 151-171), it exemplifies zero methods of treating or preventing such diseases, but merely provides IC50 inhibitory values for EGFR receptors (pg. 119). Moreover, Liu does not exemplify its compounds as pharmaceutically acceptable salts, enantiomers, diastereomers, racemates, solvates, hydrates, polymorphs, prodrugs, or isotropic variants.
Predictability in the Art
The instant claims and specification specifically teach a number of species of cancer as EGFR kinase-mediated diseases treated or prevented by its methods.
However, as taught by The University of Kansas, no cancer is 100% preventable (pg. 1).
In view of the teachings of The University of Kansas, and the state of the prior art, wherein Zhao and Liu merely exemplify IC50 values of compounds of the present invention and structurally similar compounds, a method of preventing any EGFR disease, let alone cancer, is unpredictable.
Working Examples
The instant specification provides zero examples of pharmaceutically acceptable salts, enantiomers, diastereomers, racemates, solvates, hydrates, polymorphs, prodrugs, or isotropic variants of compounds of instant formula (A), (X), or the species of claim 36.
The instant specification provides examples of four species of instantly claimed compounds that have inhibitor activity against an EGFR receptor. The instant specification provides zero examples of method of treating, let alone preventing, EGFR-mediated diseases by administering the instantly claimed compounds.
Direction and Guidance
In view of the lack of working examples and lack of written description, the instant specification does not provide sufficient direction or guidance to make pharmaceutically acceptable salts, enantiomers, diastereomers, racemates, solvates, hydrates, polymorphs, prodrugs, or isotropic variants of compounds of formula (A), (X) or species of claim 36, or provide sufficient direction or guidance use the pharmaceutically acceptable salts, enantiomers, diastereomers, racemates, solvates, hydrates, polymorphs, prodrugs, or isotropic variants of compounds of formula (A), (X), and species of claim 36, to prevent EGFR kinase mediated diseases.
Quantity of Experimentation
The quantity of experimentation required to determine all species of pharmaceutically acceptable salts, enantiomers, diastereomers, racemates, solvates, hydrates, polymorphs, prodrugs, or isotropic variants of compounds of formula (A), (X) or species of claim 36, and which of these species, in addition to the free base compounds, are useful in what amounts to treat any and every EGFR kinase-mediated diseases, would be astronomical.
A great deal of experimentation would be required starting with proof-of-concept, and proceeding through all levels of lead identification and optimization,
This amounts to invention, not development; it is an undue amount of experimentation.
This rejection can be overcome by deleting “enantiomers, diastereomers, racemates, solvates, hydrates, polymorphs, prodrugs, or isotropic variants” and the term “preventing” from the claims.
Claim Rejections - 35 USC § 102
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 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 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, 37, and 39 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by WO 2021/036922 to Zhao (published 03/04/2021, IDS of 01/13/2025, and Translation, PTO-892).
Zhao teaches:
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(pg. 84, Original), which meets the limitations of the compound of claim 1 when:
Z is CH2,
L is a bond
E is CR#R#’, wherein R# and R#’ are H
n is 5
q is 0
R3 is -OC1alkyl,
R4 and R5 are H,
R6 is a C1 alkyl,
R1 is the halogen Br
R2 is H
L1 is NR#, wherein R# is H
A is a 6 membered heteroaryl,
p is 0, and
Ra1 is
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.
See also C169, C183, C185, C188, C227, C228 (pgs. 87, 95, 97, 98, 110, Original.
"A generic claim cannot be allowed to an applicant if the prior art discloses a species falling within the claimed genus." The species in that case will anticipate the genus. See MPEP 2131.02.
Regarding claim 37, Zhao teaches pharmaceutical compositions comprising its compounds and pharmaceutically acceptable excipients (claims, pg. 22 Translation).
Regarding claim 39, Zhao teaches a method of treating and/or preventing a disease mediated by EGFR by administering one of its compounds or the pharmaceutical composition thereof (claims, pg. 22, Translation).
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 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.
Claims 2-5, 8-9, 27-28, 43 and 45 are rejected under 35 U.S.C. 103 as being unpatentable WO 2021/036922 to Zhao (published 03/04/2021, IDS of 01/13/2025, and Translation, PTO-892).
Zhao is applied as discussed above and incorporated herein.
Regarding claim 2, while Zhao teaches a compounds of instant claim 1, it differs from that of instant claim 2 in that it does not teach R6 as -NH-C(O)-CR=CR’R”.
Zhao teaches that its Z position:
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(pg. 2, Original) can be substituted with R4, which corresponds to instant R6, wherein R4 is:
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(pgs. 4, Translation).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to substitute the methyl in
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, with -NH-C(O)-CH=CH2 or -NH-C(O)-CH=C1-6alkyl, to arrive at instant claim 2. One of ordinary skill in the art would have been motivated to make such a substitution, with a reasonable expectation of success, because 922 teaches that its R4 position can be a C1 alkyl or a -NHC(O)-C2-6alkenyl.
As such, an ordinary skilled artisan would have been motivated to make such a substitution, to predictably arrive at a structurally and functionally similar compound; a prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. ‘An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties.’ In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979),” According to MPEP 2144.09(I). See also MPEP 2114.08.
Regarding claim 3,
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is a compound of (II).
Regarding claim 4, while Zhao teaches
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and
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(pgs. 95, 97 Original), it differs from that of instant claim 4 in that it does not teach the instant R6 as -NH-C(O)-CR=CR’R”.
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to substitute the methyl in
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or
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, at the instant R6 position, with -NH-C(O)-CH=CH2 or -NH-C(O)-CH=C1-6alkyl, to arrive at instant claim 4. One of ordinary skill in the art would have been motivated to make such a substitution, with a reasonable expectation of success, because Zhao teaches that its R4 position, which is instant R6, can be a C1 alkyl or a -NHC(O)-C2-6alkenyl.
As such, an ordinary skilled artisan would have been motivated to make such a substitution, to predictably arrive at a structurally and functionally similar compound; a prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. ‘An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties.’ In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979),” According to MPEP 2144.09(I). See also MPEP 2114.08.
Regarding claim 5, the modified compound of claim 4 meets the limitation of wherein “i).”
Regarding claim 8, the modified C186 compound of claim 4 teaches n is 3.
Regarding claim 9, the compound of claim 8 meets the limitation of wherein “i)”.
Regarding claim 43, Zhao teaches pharmaceutical compositions comprising its compounds and pharmaceutically acceptable excipients (claims, pg. 22 Translation).
Regarding claim 45, Zhao teaches a method of treating and/or preventing a disease mediated by EGFR by administering one of its compounds or the pharmaceutical composition thereof (claims, pg. 22, Translation).
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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 1-5, 8-9, 24-25, 27-28, 36-37, 39, and 43-46 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 20-23, 25-29, 31, and 33-34 of copending Application No. 17/637690 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other.
Note: On 06/25/2026, a Notice of Allowance was mailed for this Application. Once the patent publishes, this provisional Double Patenting rejection will be converted to a non-provisional Double Patenting rejection.
Regarding claim 1, ‘690 claims:
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(claims 8-9, 28), wherein ‘690 defines R4, which is instant R6, as Me or -NHC(O)CH=CH2 and
Y is C substituted by two RZ1, wherein RZ1 is H,
L1 is
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L2 is a bond, CH2, or CH2CH2
m is 0-3
E is an alkyl group.
As such, an ordinary skilled artisan would have been motivated to substitute the Me of (I-1-I’’’) with -NHC(O)CH=CH2, to arrive at the generic compound of instant claims 2-3, 27-28 since ‘690 teaches Me and -NHC(O)CH=CH2 as interchangeable at this position.
Alternatively, an ordinary skilled artisan would have been motivated to select -NHC(O)CH=CH2 as the R4 of (I-1-F), to arrive at the compound of instant claims 4-5, 8-9, 24-25, 36, since ‘690 teaches R4 as -NHC(O)CH=CH2.
Regarding claims 37, and 43-44 ‘690 claims compositions comprising its compounds and pharmaceutically acceptable excipients (claim 29).
Regarding claims 39, and 45-46, ‘690 claims methods of treating diseases mediated by EGFR kinase by administering to a subject, the instantly claimed compounds (claims 31, 33-34).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Free of the Prior Art
Claims 24-25, 27-28, 31-32 and 36 are free of the prior art.
The closest prior art is WO 2021/036922 to Zhao (published 03/04/2021, IDS of 01/13/2025, and Translation, PTO-892).
Regarding claims 24-25, Zhao does not teach a compound wherein R6 is -NH-C(O)-CR=CR’R” or -NH-C(O)-C≡CR’, A is absent, and R3 is H.
Regarding claims 27-28, Zhao does not teach a compound wherein R6 is -NH-C(O)-CR=CR’R” or -NH-C(O)-C≡CR’ and A is absent.
Regarding claims 31-32, Zhao does not teach a compound wherein the instant Ra1 position is N(Rs)S(O)2CH3.
Regarding claim 36, Zhao does not teach the species of instant claim 36.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN WELLS whose telephone number is (571)272-7316. The examiner can normally be reached M-F 7:00-4:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James (Jim) Alstrum-Acevedo can be reached on 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LAUREN WELLS/Examiner, Art Unit 1622
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