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
Priority
Acknowledgments are made that this application claims the priority to the following:
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Information Disclosure Statement
The information disclosure statement (IDS), dated 12/27/2022, comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, they have been placed in the application file and the information therein has been considered as to the merits.
Claim Objections/Sequence Compliance
Claims and Specification are objected to because of the following informalities: 37 CFR 1.821(d) states that where the claims and specification recite a sequence, the sequence identifier (SEQ ID NO:) must be included. It appears that applicants have not provided a sequence listing. Appropriate correction is required.
Election/Restriction
REQUIREMENT FOR UNITY OF INVENTION
As provided in 37 CFR 1.475(a), a national stage application shall relate to one invention only or to a group of inventions so linked as to form a single general inventive concept (“requirement of unity of invention”). Where a group of inventions is claimed in a national stage application, the requirement of unity of invention shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features. The expression “special technical features” shall mean those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art.
The determination whether a group of inventions is so linked as to form a single general inventive concept shall be made without regard to whether the inventions are claimed in separate claims or as alternatives within a single claim. See 37 CFR 1.475(e).
When Claims Are Directed to Multiple Categories of Inventions:
As provided in 37 CFR 1.475 (b), a national stage application containing claims to different categories of invention will be considered to have unity of invention if the claims are drawn only to one of the following combinations of categories:
(1) A product and a process specially adapted for the manufacture of said product; or
(2) A product and a process of use of said product; or
(3) A product, a process specially adapted for the manufacture of the said product, and a use of the said product; or
(4) A process and an apparatus or means specifically designed for carrying out the said process; or
(5) A product, a process specially adapted for the manufacture of the said product, and an apparatus or means specifically designed for carrying out the said process.
Otherwise, unity of invention might not be present. See 37 CFR 1.475 (c).
Restriction is required under 35 U.S.C. 121 and 372.
This application contains the following inventions or groups of inventions which are not so linked as to form a single general inventive concept under PCT Rule 13.1.
In accordance with 37 CFR 1.499, applicant is required, in reply to this action, to elect a single invention to which the claims must be restricted.
Group I, claim(s) 1-9, 11 and 16-17, drawn to a method of synthesizing plecanatide with the recited synthetic steps.
Group II, claim(s) 10 and 18, drawn to a method of synthesizing plecanatide with the recited synthetic steps. These differ from group I in method steps, for example, different starting materials etc.
Group III, claim(s) 19-23, drawn to a peptide compound for preparing plecanatide selected from the listed peptides.
The groups of inventions listed above do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons:
Groups I-III lack unity of invention because even though the inventions of these groups require the technical feature of plecanatide, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of US2016/0145307A1, which teaches plecanatide.
During a telephone conversation with Morgan Stevenson on 12/16/2025, a provisional election was made with traverse to prosecute the invention of group I, claims 1-9, 11 and 16-17. Affirmation of this election must be made by applicant in replying to this Office action. Claims 10 and 18-23 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
The examiner has required restriction between product or apparatus claims and process claims. Where applicant elects claims directed to the product/apparatus, and all product/apparatus claims are subsequently found allowable, withdrawn process claims that include all the limitations of the allowable product/apparatus claims should be considered for rejoinder. All claims directed to a nonelected process invention must include all the limitations of an allowable product/apparatus claim for that process invention to be rejoined.
In the event of rejoinder, the requirement for restriction between the product/apparatus claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103 and 112. Until all claims to the elected product/apparatus are found allowable, an otherwise proper restriction requirement between product/apparatus claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowable product/apparatus claim will not be rejoined. See MPEP § 821.04. Additionally, in order for rejoinder to occur, applicant is advised that the process claims should be amended during prosecution to require the limitations of the product/apparatus claims. Failure to do so may result in no rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
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 of this title, 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 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 1-9, 11 and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Shailubhai (WO2014/197720A2; see applicants filed IDS dated 12/27/2023) in view of Adak (WO2020/115566A1; see applicants filed IDS dated 12/27/2023) and Nyfeler (Method in Molecular Biology, vol.35, Peptide Synthesis Protocols, Ed. Pennington and Dunn, 1994, Ch.15, 303-316), Volkmer-Engert (J.Peptide Res., 1998, 51, 365-369) and Alberico (Org. Process Res. Dec., 2018, 22, 760-772).
For claims 1-5:
Shailubhai teaches synthesis of plecanatide by fragment coupling comprising the following:
(a) Preparation of Fmoc-Cys(Acm)-Leu-OtBu and deprotecting it to H-Cys(Acm)-Leu-OtBu, these fragments are identical to applicants Formula A and A1. These amino acids are corresponds to 15th and 16th amino acids in 16 amino acid length of plecanatide.
(b) Coupling of H-Cys(Acm)-Leu-OtBu with Fmoc-Cys(Acm)-Val-Asri(Trt)-Va!-Ala-Cys(Trt)-Thr(tBu)-Gly-OH [these amino acids corresponds to 7-14 amino acids in 16 amino acid length of plecanatide], which results in 7-16 amino acids in 16 amino acid length of plecanatide with the same protecting groups from their patent fragments.
(c) Coupling of Boc-Asn(Trt)-Asp(OtBu)-Glu(OfBu)-Cys(Trt)-Glu(OtBu)-Leu-OH [these amino acids corresponds to 1-6 amino acids in 16 amino acid length of plecanatide] with the resulted “fragment with 7-16 amino acids” from above (b), which results in side chain protected plecanatide.
(d) the above side chain protected linear plecanatide can be deprotected to give partially protected linear plecanatide, wherein two Cys(Acm) at 7 and 15 positions are intact, whereas Cys at positions 4 and 12 get oxidized by H2O2.
(e) the above steps is followed by simultaneous removal of Cys(Acm) groups and disulfide formation with iodine to give crude dicyclic plecanatide, which is purified and concentrated. [See pages 13-19].
Difference is that Shailubhai silent on applicant’s claimed specific fragments of plecanatide, other than fragments A and A1, in their synthetic method. In other words, Shailubhai utilized fragments, viz., 15-16, 7-14 and 1-6 of plecanatide, whereas claimed fragments require, for example, viz., 15-16, 9-16 and 1-8 of plecanatide. However, nothing in the record or shown data on the advantage of the claimed specific fragments compared to the fragments of Shailubhai.
Synthesis of plecanatide by using various fragments of plecanatide is known in the art. For example, Adak teaches synthesis of plecanatide using fragments, viz., 1-5 and 6-16 etc. [see pages 9-10]. Peptide synthesis using fragment coupling is also well known in the art. For example, Nyfeler in a review article teaches advantages of fragment coupling [see pages 303-305], such as availability, stability and purification of fragments etc., and also provided guidelines for making peptides using fragment synthesis [see section 3].
With regard to charcoal in oxidizing deprotected formula F, though Shailubhai is silent on this limitation, but charcoal is known to assist intramolecular disulfide bond formation in peptides, as evidenced from the teachings of Volkmer-Engert [see abstract].
Therefore, skilled person in the art would choose suitable fragments in making a peptide based on synthetic method to make a fragment, stability of fragment and purification of fragment, and so claimed method is obvious over the cited art.
For claim 6:
Shailubhai silent of HOAt in the presence of EDC.HCl for coupling reaction. However, selection of coupling reaction is based on protecting groups and these are interchangeable. For Alberico teaches that EDC.HCl is very often the carbodiimide of choice because it is easy to remove during the workup and further teach HOAt is better than HOBt [see page 762, 1st and 2nd paragraphs in left column].
For claim 7:
Shailubhai silent of charcoal, but charcoal is known to assist intramolecular disulfide bond formation in peptides, as evidenced from the teachings of Volkmer-Engert [see abstract].
For claims 8-9
Shailubhai teach RP-HPCL with solvents ACN and AcOH [see Schemes 7 and 9; examples 4-5. However, the concentrations and pH are result effective variables and so, a skilled person in the art would determine suitable conditions through a routine experimentation.
For claim 11:
Shailubhai teach purity of 96.1% and yield 68 g [see Example 4].
For claims 16-17:
As explained under For claims 1-5 above, skilled person in the art would choose suitable fragments in making a peptide based on synthetic method to make a fragment, stability of fragment and purification of fragment, and so claimed method is obvious over the cited art.
Based on the above established facts from the cited prior art, it appears that all the claimed elements, i.e, applicants individual components and synthetic methods making plecanatide from its various fragment, were known in the prior art, and one skilled person in the art could have combined the elements as claimed by known relationships, with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art.
The motivation to combine art can arise from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. See MPEP 2144.07. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited reference and to make the instantly claimed method with a reasonable expectation of success.
The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art or drawn from a convincing line of reasoning based on established scientific principles or legal precedent, that some advantage or expected beneficial result would have been produced by their combination. In re Sernaker, 702 F.2d 989, 994-95, 217 USPQ 1, 5-6 (Fed. Cir. 1983). In the instant case, one is simply replacing known fragment with another possible fragment of plecanatide.
Conclusion
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.
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, 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