Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application is a DIV of 17/719,870 (04/13/2022 ABN)
17/719,870 is a CON of PCT/US2021/042956 (07/23/2021)
PCT/US2021/042956 has PRO 63/056,210 (07/24/2020).
The scope of the claims, including claim 1 formula, do not find support in the provisional application, in particular at least the hydrazineyl group. As a result, the earliest priority date of the claims is determined to be 7/23/2021.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1), 1.835(a)(2), or 1.835(b)(2) is missing, defective or incomplete. The incorporation by reference paragraph refers to the file in kilobytes, not bytes.
Required response - Applicant must:
• Provide a substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specific deficiency - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.831(a) and 1.831(b). However, this application fails to comply with the requirements of 37 CFR 1.831-1.834. The examiner has noted that the disclosure includes nucleotide and peptide sequences that fall within the rule on at least pages 115 and 116.
Required response - Applicant must provide:
• A replacement “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2., as well as
• A statement that identifies the location of all additions, deletions, or replacements of sequence information in the “Sequence Listing XML” as required by 1.835(b)(3);
• A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.835(b)(4);
• A statement that the “Sequence Listing XML” includes no new matter in accordance with 1.835(b)(5); and
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(b)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Election/Restrictions
Applicant's election without traverse of Group I, claims 1-18, in the reply filed on 11/11/25 is acknowledged.
Applicant also elected the following species in a call with Eric Williams on 12/18/2025:
benzyl ((2S,3R)-1-(((S)-1-(2-(3-amino-3-oxopropyl)-2-(2-chloroacetyl)hydrazineyl)-3- cyclohexyl-1-oxopropan-2-yl)amino)-3-(tert-butoxy)-1-oxobutan-2-yl)carbamate
p. 10 claims, compound 10:
PNG
media_image1.png
68
780
media_image1.png
Greyscale
having the following structure:
PNG
media_image2.png
200
400
media_image2.png
Greyscale
determined to read on the formula of claim 1 when
W is -C(O)C1-alkyl substituted by Cl;
R6 is C2-alkyl substituted by C(O)NRaRb; Ra and Rb are H;
R2, R3, R5 are H
p is 2
R4 (1) is C1 alkyl substituted by Rb of C6 cycloalkyl;
R4 (2) is C2 alkyl substituted by C4 alkoxy
R1 is C1alkoxy substituted by Ra of C6 aryl.
Thus, the elected species reads on claims 1-6, 16-17.
As detailed in the following rejections, the generic claim encompassing the elected species was not found patentable. Therefore, the provisional election of species is given effect, the examination is restricted to the elected species only, and claims not reading on the elected species are held withdrawn. MPEP 803.02; Ex parte Ohsaka, 2 USPQ2d 1460, 1461 (Bd. Pat. App. lnt. 1987). Accordingly, claims 7-15 are hereby withdrawn.
Should applicant, in response to this rejection of the Markush-type claim, overcome the rejection through amendment, the amended Markush-type claim will be reexamined to the extent necessary to determine patentability of the Markush-type claim. See MPEP 803.02.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 1-6, 17 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor at the time the application was filed, had possession of the claimed invention.
Applicant filed a 2/13/2023 preliminary amendment to claim 1 which has amended language such as in claim 1:
PNG
media_image3.png
169
793
media_image3.png
Greyscale
With the explanation of support as:
PNG
media_image4.png
100
781
media_image4.png
Greyscale
The Examiner has reviewed the specification and original disclosure and could not locate support for the claim as amended, in particular with respect to changing SO4 to SO3. The examiner could not locate support for such a new limitation, nor does there appear to be a written description of the limitation in the application as filed. See Hyatt v. Dudas, 492 F.3d 1365, 1370, 83 USPQ2d 1373, 1376 (Fed. Cir. 2007) (holding that "[MPEP] § 2163.04 (I)(B) as written is a lawful formulation of the prima facie standard for a lack of written description rejection."). There is no literal support for the added limitation and one of skill in the art would not recognize that Applicant possessed the claim scope.
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 1-2 and 17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kati et al. (Archives of Biochemistry and Biophysics (1999), 362(2), 363-375).
Kali teaches compounds including the following compound in Table 3, compound “18”, (Boc-Ile-Phe-AzaGln-CH2-Br) having the following structure:
PNG
media_image5.png
259
343
media_image5.png
Greyscale
And reading on claim 1’s formula
PNG
media_image6.png
95
198
media_image6.png
Greyscale
when
W is -C(O)C1-alkyl substituted by Br;
R6 is C2-alkyl substituted by C(O)NRaRb; Ra and Rb are H;
R2, R3, R5 are H
p is 2
R4 (1) is C1 alkyl substituted by Rb of C6 aryl;
R4 (2) is C4 alkyl;
R1 is C4 alkoxy.
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.
Claims 1-6, 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al. (US20050143320) in view of Kati et al. (Archives of Biochemistry and Biophysics (1999), 362(2), 363-375) and Akaji (Amino Acids, Pept. Proteins, 2018, 42, 228–279).
Yang teaches protease inhibitors of “coronaviral 3CL proteases” and “rhinoviral 3C protease” with compound 134 (claimed):
PNG
media_image7.png
238
431
media_image7.png
Greyscale
Yang’s compound differs from the elected species by the right-hand side of the compound.
Kati teaches structurally similar protease inhibitors compounds such as in Table 3 with the acetyl bromide warhead having significant impact at the P1 site:
PNG
media_image8.png
380
502
media_image8.png
Greyscale
and was successful in the same context. Kati teaches success with the modification to a bormomethylketonehydrazide.
Akaji teaches the successful approach of utilizing warhead approach on coronavirus 3CL protease (p. 248-251). Akaji teaches success with the inhibitor 17 (same compound as Yang):
PNG
media_image9.png
204
325
media_image9.png
Greyscale
As well as modifications that implemented the halomethyl ketone warhead (Tables 5 and 6), including specifically the chloro-, and bromo-methylketones shown in Table 6.
One of ordinary skill in the art of protease inhibitors following the teaching of Yang would have considered modifications of compound 134 in view of the success of Kati and Akaji in utilizing the reactive warhead group to create a more effective protease inhibitor. One of ordinary skill in the art would have had a reasonable expectation of success because of the similarities in structure of the prior art compounds as well as the common protease targets. As evidenced by Kati and Akaji, the level of skill in the art is very high such that one of ordinary skill in the art would consider routine the combination of elements from the teaching of the art including modifying the structure to incorporate a warhead element. One of ordinary skill in the art would have recognized that the results of the combination would be predictable due to the well-known nature and optimizations routinely performed in the art. Thus, one of ordinary skill in the art would have arrived at the invention as claimed before the effective filing date with a reasonable expectation of success.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT H HAVLIN whose telephone number is (571)272-9066. The examiner can normally be reached 9am - 6pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney Klinkel can be reached at 571-270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ROBERT H HAVLIN/Primary Patent Examiner, Art Unit 1626