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 (i.e., claims 100-102 and 104-106 drawn to a compound comprising the amino acid sequence of SEQ ID NOs: 2 or 11) in the reply filed on August 17, 2026, is acknowledged. Additionally, Applicant's election with traverse of Species A (i.e., a single and specific compound as SEQ ID NO: 11) in the reply filed on August 17, 2026, is acknowledged. Applicant traverse the restriction but did not specifically provide arguments for the traversal. Thus, the traversal is found unpersuasive.
The requirement is still deemed proper and is therefore made FINAL.
Please note that the Examiner is interpreting Applicant’s election such that SEQ ID NO: 11 is not optionally substituted with one or more protected groups.
Status of Claims
Claims 1-99 were originally filed on October 2, 2025.
The amendment received on October 2, 2025, canceled claims 1-99 and added claims 100-107.
Claims 100-107 are currently pending and claims 104-106 are under consideration as claims 100-103 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, and claim 107 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on August 17, 2026.
Priority
The present application is a continuation of U.S. Application No. 19/118,209, filed on April 3, 2015, which claims status as a 371 (National Stage) of PCT/US2023/076098 filed October 5, 2023, and claims priority under 119(e) to U.S. Provisional Application Nos. 63/477,742 filed on December 29, 2022, and 63/378,397 filed on October 5, 2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on October 2, 2025, is being considered by the examiner.
Sequence Interpretation
For claims 104 and 106, with respect to SEQ ID NO: 11, please note that the Examiner is interpreting the scope as open-ended requiring 100% identity to SEQ ID NO: 11 with any N- and/or C-terminal additions.
For claim 106, with respect to SEQ ID NO: 1, please note that the Examiner is interpreting the scope as open-ended requiring 100% identity to SEQ ID NO: 1 with any N- and/or C-terminal additions.
Specification
Please note, the specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification. MPEP § 608.01.
The disclosure is objected to because of the following informalities: the specification teaches/depicts a number of peptides in a linear and/or chemical structure form without a SEQ ID NO: (See instant, [0013]-[0017], [0024], [0029], [0034], [0039], [0049], [0054], [0062], [0069], [0076], [0083], [0090], [0094], [0098], [0102], [0106]-[0109], [0112]-[0119], [0121]-[0122], [0132], [0138]-[0141], [0148], [0157], [0170], [0176], [0195], [0205], [0218], [0228], [0239], [0253], etc.). Please note that the Examiner has not cited all the paragraphs that recite structures/sequences that require a sequence identifier. Pursuant to MPEP 2422 and 37 CFR 1.821(a), any amino acid sequence at least 4 defined amino acids in length requires a sequence identifier. Moreover, pursuant to MPEP 2422.01(III), if the applicant presents the sequence as a string of particular nucleotide bases or amino acids, whether by way of symbols, words or chemical structure, it is necessary to include the sequence in the "Sequence Listing" regardless of whether the applicant considers the sequence to be prior art, so long as the sequence meets the criteria of 37 CFR 1.821(a). Thus, amino acid sequences depicted as a chemical structure also requires a sequence identifier. Additionally, please update the Sequence Listing, if necessary. Appropriate correction is required.
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.
Claims 104-105 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Frederick et al., Org. Process Res. Dev. 25:1628-1636 (2021) (cited in the IDS received on (10/2/25).
For claims 104-105, Frederick et al. discloses the structure of tirzepatide in Figure 1 as:
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(See Frederick, pg. 1629, Figure 1). When comparing instant SEQ ID NO: 11 with the tirzepatide structure there is 100% identity with residues 10-39 of tirzepatide where the C-terminus is amidated, and the Lys at position 20 (i.e., position 11 of instant SEQ ID NO: 11) is modified with (2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(gamma-Glu)-CO-(CH2)18-CO2H. As discussed in the “Sequence Interpretation” section, the scope of claim 104-105 requires 100% identity to SEQ ID NO: 11, but with any N- and/or C-terminal additions; and the scope of claim 104 does not require that SEQ ID NO: 11 is modified with one of the recited protecting groups. As such, the full length tirzepatide sequence is encompassed by the scope of instant claims 104-105. Furthermore, since the instantly claimed composition only structurally requires the compound of claim 104 without any further structural components, the disclosure of tirzepatide constitutes a composition comprising instant SEQ ID NO: 11. Therefore, Frederick’s disclosure satisfies the claim limitation of a compound comprising SEQ ID NO: 11 as recited in instant claim 104, and a composition comprising the compound comprising SEQ ID NO: 11 as recited in instant claim 105.
Accordingly, Frederick’s disclosure anticipates instant claims 104-105.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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 under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
103 - KSR Examples of 'Rationales' Supporting a Conclusion of Obviousness(Consistent with the "Functional Approach" of Graham)
Further regarding 35 USC 103(a) rejections, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) (KSR) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Also, a reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976).
Claims 104-106 are rejected under 35 U.S.C. 103 as being unpatentable over Yadav et al. WO 2023/089594 A1 published on May 25, 2023 (effective filing date of November 22, 2021) (cited in the IDS received on 10/2/25).
For claims 104-106, ‘594 teaches tirzepatide or a pharmaceutically acceptable salt thereof where the tirzepatide or a pharmaceutically acceptable salt comprises not more than 0.5% of a single major impurity or substantially free (See ‘594 claims 10 and 41) where the major impurity is a compound of SEQ ID NOs: 11-13, 15, or 17-24 or a pharmaceutically acceptable salt thereof (See ‘594 claims 11 and 41). When comparing ‘594 SEQ ID NOs: 11-14, with instant SEQ ID NO: 11, there is 100% identity with residues 10-39 of each of ‘594’s SEQ ID NOs: 11-13. As discussed in the “Sequence Interpretation” section, the scope of claim 104-105 requires 100% identity to SEQ ID NO: 11, but with any N- and/or C-terminal additions; and the scope of claim 104 does not require that SEQ ID NO: 11 is modified with one of the recited protecting groups. As such, the full length tirzepatide sequence is encompassed by the scope of instant claims 104-105.
Furthermore, ‘594 teaches that the side chain of amino acids are free or protected with a suitable protecting group of SEQ ID NOs: 11-24 (See ‘594, pg. 14, last paragraph). Examples of protecting groups include a Fmoc group, a tert-butyl (i.e., tBu) group, tert-butyloxycarbonyl ( i.e., -Boc) group, a 4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)-3-methylbutyl (i.e., IVDde) group, and a trityl (i.e., -Trt) group (See ‘594, pg. 23, 2nd paragraph). The hydroxyl groups of serine, tyrosine or threonine can be protected with -tBu, the amino a group of lysine can be protected with -Boc and IVDde group, the carboxylic acid groups of aspartate or glutamate can be protected with -tBu groups, and an amide group of glutamine can be protected with a trityl group (See ‘594, pg. 23, 2nd paragraph). As such, the side chain of the Lys at position 20 of ‘594’s SEQ ID NOs: 11-13 (i.e., the side chain is modified in tirzepatide with (2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(gamma-Glu)-CO-(CH2)18-CO2H) would be free or protected by -Boc and/or IVDde groups. Thus, ‘594’s SEQ ID NOs: 11-13 encompass where the side chain of the lysine at position 20 of tirzepatide is protected with a -Boc group thereby constituting a compound comprising SEQ ID NO: 11 that is substituted with a -Boc group as recited in instant claims 104-106. Moreover, since the instantly claimed composition only structurally requires the compound of claim 104 without any further structural components, constitutes a composition comprising instant SEQ ID NO: 11 where the side chain of the lysine at position 20 of tirzepatide is protected with a -Boc group. Plus, since ‘594 claims where tirzepatide comprises not more than 0.5% of a single major impurity or substantially free where the major impurity is a compound of SEQ ID NOs: 11-13, it would necessarily follow that the composition comprising tirzepatide and a low amount of an impurity such as one or more of 594’s SEQ ID NOs: 11-13 where the side chain of the lysine at position 20 of tirzepatide is protected with a -Boc group, constitutes a composition comprising a compound comprising instant SEQ ID NO: 11 and SEQ ID NO: 1 (i.e., tirzepatide) as recited in instant claim 106.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant application to follow the teachings of ‘594 and purify a composition comprising an impurity compound of instant SEQ ID NO: 11 where the side chain of the lysine at position 13 is protected with a -Boc group and tirzepatide where the impurity is present in an amount not more than 0.5%. One of ordinary skill in the art at the time the invention was made would have been motivated to do so because purifying a tirzepatide composition was known to result not more than 0.5% of a single major impurity or substantially free where the major impurity is a compound of SEQ ID NOs: 11-13 and because the single major impurity was known to contain one or more amino acids where the side chain of the side chain of amino acids were known to be free or protected with a suitable protecting group such as a Fmoc group, a tert-butyl (i.e., tBu) group, tert-butyloxycarbonyl ( i.e., -Boc) group, a 4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)-3-methylbutyl (i.e., IVDde) group, and a trityl (i.e., -Trt) group as taught by ‘594. One of ordinary skill in the art at the time the invention was made would have had a reasonable expectation of success given that the composition of ‘594 comprised tirzepatide and not more than 0.5% of a single major impurity or substantially free where the major impurity is a compound of SEQ ID NOs: 11-13, 15, or 17-24. Therefore, utilizing any one of SEQ ID NOs: 11-13 where the side chain of the lysine at position 20 is protected with a -Boc group would support the purification of a composition comprising an impurity compound of instant SEQ ID NO: 11 where the side chain of the lysine at position 13 is protected with a -Boc group and tirzepatide where the impurity is present in an amount not more than 0.5% by constituting the simple substitution of one known element for another to obtain predictable results; and/or the use of known technique to improve similar devices (methods, or products) in the same way; and/or the application of a known technique to a known device (method, or product) ready for improvement to yield predictable results; and/or some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention pursuant to KSR.
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to THEA D' AMBROSIO whose telephone number is (571)270-1216. The examiner can normally be reached M-F 11:00 to 8:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached at 571-270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/THEA D' AMBROSIO/Primary Examiner, Art Unit 1654
