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 .
Status of the application
Please note that for the reasons internal to the USPTO, this application has been reassigned.
Receipt of applicant’s remarks and claim amendments filed on 03/27/2026 are acknowledged.
In light of claim amendments, previous 102(a)(1) rejection over Loidl is withdrawn.
However, applicants arguments for previous 112(b), 102(a)(1) over Schoenleber, and 103 rejection are found no persuasive and are maintained and modified to address claim amendments.
Response to Arguments
Applicants’ argue that Schoenleber discloses nowhere the combined use of a pseudoproline dipeptide and a non-pseudoproline dipeptide.
In fact Schoenleber does teach these combination. For example, Schoenleber teaches a process, wherein the pseudoproline dipeptide is Fmoc-Val-Ser(Psi(Me,Me)pro)-OH (see 0207) and Schoenleber further teaches that wherein the non-pseudoproline dipeptide can be Boc-His(Trt)-Aib-OH or Boc-His(Trt)-Ala-OH and Trt is referred to as “1-Trit” (see 0197).
Applicants further argue that Li is merely cited in connection with the additional limitation of dependent claims 4 and 5 and cannot remedy the deficiencies discussed above in connection with claim 1, from which both claims 4 and 5 depend indirectly.
As explained above, Schoenleber teaches both pseudoproline and non-pseudoproline petpides. The purpose of Li is to show that a method for synthesizing semaglutide comprising stepwise coupling of dipeptide fragments and tripeptide fragments with an amino acid N-terminus Fmoc protection to obtain semaglutide (see [0025], [0119]).
Applicants further pointed to Examples 1-3 of Schoenleber, it is not clear what applicants intend to conclude. Moreover, claims do not require any shown data limitations.
Claim Rejections - 35 USC § 112
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 1-8 and 13 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.
Claim 1 recites (i) “preparation of glucagon-like-peptide-1 represented by formula (1)”, (ii) “synthesizing a protected peptide” and (iii) “the peptide is semaglutide”. It is not clear whether semaglutide represents former two.
The claimed steps are very vague, and they do not specify which protected peptide is synthesized and which protected amino acids and dipeptides are used. As such, any protected peptide and any protected amino acids or dipeptides may be used. This represents a lack of union between the body of the claims and the subject matter that Applicant regards as the invention. Specifically, the language of the preamble and embodiments in the specification suggest that Applicant regards subject matter directly related to the synthesis of liraglutide and semaglutide as the subject matter of the invention, but the language of the claims is general and can be used for any protected peptide. Here, Applicant has not particularly pointed out and distinctly claimed the subject matter which they regard as the invention, as there is a lack of direct connection between the body of the claims and the subject matter regarded as the invention. It is suggested that Applicant revise the claim language to distinctly claim the subject matter they regard as the invention. More specifically, it is advised that Applicant distinctly claim the synthesis of the peptides that they regard as the invention.
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 (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 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, 3, 6-8, and 13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Schoenleber (US 20210009631 A1).
With regard to claim 1, Schoenleber teaches a process of the preparation of glucagon-like peptide-1 agonist peptide represented by the following formula: H(Aib)EGTFTSDVSSYLEGQAAK(R)EFIAWLVRGRG (see Table 1). The method comprises synthesizing a protected peptide on a solid phase by stepwise coupling of a protected amino acid and a protected dipeptide (see claims 43, 52, and 70), the protected dipeptide comprising pseudoproline dipeptide (see claim 53), cleaving the protected peptide from the solid phase (see [0038]), and deprotecting the protected peptide to obtain the peptide (see [0038]), wherein R is -AEEA-AEEA-γ-Glu-octadecanedioic acid (see claim 83), referred to as AEEAc-AEEAc-g-Glu-17-carboxyheptadecanoyl (see claim 83). It is worth noting that, as written, the histidine is at the N terminus of the peptide and would be protonated under physiological conditions (bound to a hydrogen), and the glycine is at the C terminus and would be bound to an OH. As such, it is the examiner’s position that the leftmost H and rightmost OH groups of formula (1) of the instant application are merely a notational difference between formula (1) and Table 1 of Schoenleber.
With regard to claim 2, Schoenleber teaches the process discussed above wherein the pseudoproline dipeptide is Fmoc-Val-Ser(Psi(Me,Me)pro)-OH (see [0207]).
With regard to claim 3, Schoenleber teaches the process discussed above wherein the dipeptide derivative can be Boc-His(Boc)Aib-OH (see [0197]).
With regard to claim 6, Schoenleber teaches the process described above wherein the non-pseudoproline dipeptide can be Boc-His(Trt)-Aib-OH or Boc-His(Trt)-Ala-OH and Trt is referred to as “1-Trit” (see [0197]).
With regard to claim 7, Schoenleber teaches the process described above wherein the coupling of the non-pseudoproline dipeptide with the protected amino acid is carried out in presence of a coupling reagent consisting of DEPBT and DIPEA (see [0184-0187]).
With regard to claim 8, Schoenleber teaches the process discussed above wherein the protected amino acid is Fmoc-Lys(Alloc)-OH) (see [0323]).
With regard to claim 13, Schoenleber teaches the method discussed above wherein there is a step of purification after cleaving the peptide from the solid phase and deprotecting the protected peptide to obtain the peptide (see [0249]).
Accordingly, claims are fully anticipated.
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.
Claims 4 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Schoenleber (US 20210009631 A1) in view of Li (CN109311961; see IDS submitted on 05/18/2023).
Schoenleber teaches the method discussed above in 102 rejection and applied to claims 1 and 3. Schoenleber does not teach the method wherein the non-pseudoproline dipeptide comprises at least one selected from the group consisting of Boc-Arg(Pbf)Gly-OH and Boc-Glu(OtBu)Gly-OH.
Li teaches a method for synthesizing semaglutide, the method comprising stepwise coupling of dipeptide fragments and tripeptide fragments with an amino acid N-terminus Fmoc protection to obtain semaglutide (see [0025], [0119]). They further teach that their method, which includes the use of Boc-Glu(OtBu)Gly-OH in the synthesis of the peptide, led to a 56.1% yield of Boc-His(trt)-Aib-Glu(OtBu)-Gly-OH with a purity of 96.8% (see [0201-0205]). Boc-His(trt)-Aib-Glu(OtBu)-Gly-OH is then used as a peptide in the preparation of the peptide resin in Example 31 (see [0249]-0252]). Using the peptides of this invention, Li teaches that the synthesis of dipeptide fragments, tripeptide fragments, tetrapeptide fragments, pentapeptide fragments, or combinations thereof with Gly-resin can be carried out simultaneously during the semaglutide synthesis process, shortening the synthesis time (see [0131]). This provides a motivation to use the aforementioned peptides, including Boc-His(trt)-Aib-Glu(OtBu)-Gly-OH, in order to shorten the synthesis time. Here, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant application to combine the references of Li and Schoenleber to synthesize semaglutide with Boc-His(trt)-Aib-Glu(OtBu)-Gly-OH on account of the shortened synthesis time taught by Li.
With regard to claim 4, Schoenleber teaches the process described and applied above wherein the non-pseudoproline dipeptide derivative can be Boc-His(Boc)Aib-OH, but Schoenleber does not teaches that the non-pseudoproline dipeptide can be Boc-Arg(Pbf)Gly-OH or Boc-His(Trt)Ala-OH.
As discussed above, Li teaches the aforementioned method wherein the non-pseudoproline dipeptide can be Boc-Glu(OtBu)-Gly-OH (see [0201]-[0205]). Given the reasoning provided above, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant application to combine the references of Li and Schoenleber to synthesize semaglutide wherein the non-pseudoproline dipeptide is Boc-Glu(OtBu)-Gly-OH.
With regard to claim 5, Schoenleber teaches the process as described and applied to claims 1-4, 6-8, and 10, 12, and 13 above. Schoenleber does not explicitly teach the process wherein the non-pseudoproline dipeptide comprises no more than 3 types of dipeptide. With regard to the use of non-pseudoproline dipeptides, Schoenleber teaches that the coupling of His derivatives is preferably carried out by using an amino acid derivative, like Fmoc-His(1-Trt)-OH, or a similar non-pseudoproline dipeptide to optimize racemization (see [0197]). Specifically, they teach the use of the following non-pseudoproline dipeptides: Fmoc-His(1-Trit)-Aib-OH, Boc-His(1-Trit)-Aib-OH, Boc-His(Boc)-Aib-OH, Fmoc-His(Boc)-Aib-OH, Fmoc-His(1-Trit)-Ala-OH, Boc-His(1-Trit)-Ala-OH, Boc-His(Boc)-Ala-OH, or Fmoc-His(Boc)-Ala-OH (see [0197]). Here, Schoenleber imply the use of a single amino acid derivative, like Fmoc-His(1-Trt)-OH, or a single non-pseudoproline dipeptide, like Boc-His(Boc)-Aib-OH, in order to optimize racemization. Seeing as they do not require a non-pseudoproline dipeptide, as a preferred embodiment utilizes Boc-His(Boc)-OH in place of the dipeptide (see [0197]), Schoenleber teaches embodiments that have fewer than 3 types of non-pseudoproline dipeptides.
Further, Schoenleber teaches that the use pseudoproline dipeptides in the synthesis of semaglutide is beneficial because pseudoproline dipeptides advantageously suppress peptide aggregation and hence the formation of by-products due to inefficient synthesis (see [0206], [0208]). Here, they provide a clear motivation to use, try, or experiment to use a greater share of pseudoproline dipeptides as opposed to non-pseudoproline dipeptides on account of their advantageous ability to suppress peptide aggregation. Given this motivation, it would have been obvious to one of ordinary skill prior to the effective filing date of the instant application to try to experiment to maximize the number of pseudoproline dipeptides and, thereby, minimize the number of non-pseudoproline dipeptides with a reasonable expectation of conferring greater ability to suppress aggregation. As such, Schoenleber provides a clear motivation to try the process described above wherein the non-pseudoproline dipeptide comprises no more than 3 types of dipeptide. This practice of routine optimization would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant application and would have reasonably led to embodiments with no more than 3 types of dipeptide with a reasonable expectation of decreasing aggregation.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUDHAKAR KATAKAM whose telephone number is (571)272-9929. The examiner can normally be reached 8:30 am to 5 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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SUDHAKAR KATAKAM
Primary Examiner
Art Unit 1658
/SUDHAKAR KATAKAM/Primary Examiner, Art Unit 1658
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