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
Applicant's election with traverse of Group I, claims 1-12, in the reply filed on 04/22/2026 is acknowledged. The traversal is on the ground(s) that “the Examiner has not made a persuasive showing that there would be an undue burden in examining the subject matter of all claims in a single application.” This is not found persuasive, because the Groups recited in the Requirement are independent or distinct, see p. 2 and 3 of the Requirement. Furthermore examination of all the Groups would require a different field of search (e.g., searching different classes/subclasses or electronic resources, or employing different search strategies or search queries). The requirement is still deemed proper and is therefore made FINAL.
Claims 1-20 are pending.
Claims 13-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04/22/2026.
Claims 1-12 are under examination on the merits.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 1-12 have an effective filing date of 05/26/2022, corresponding to PRO 63/346,099.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 08/14/2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Rejections
35 U.S.C. 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.
Claim 11 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kramer et al. (Biomacromolecules, 13: 1719-1723, 2012, IDS).
Kramer et al. teach “a new ‘click’ type reaction for polypeptide modification based on the chemoselective alkylation of thioether groups in methionine residues. The controlled synthesis of methionine polymers and their alkylation by a broad range of functional reagents to yield stable sulfonium derivatives are described. These ‘methionine click’ functionalizations are compatible with deprotection of other functional groups, use an inexpensive, natural amino acid that is readily polymerized and requires no protecting groups, and allow the introduction of a diverse range of functionality and reactive groups onto polypeptides.” See Abstract. At p. 1720, second column, Kramer et al. teach alkylation reactions that may be used to generate sulfonium derivatives of poly methionine. At the top of p. 1721, second column, Kramer et al. demonstrate a reaction that yields alkylated poly methionine, and the products of these reactions circled below appear to meet the limitations of the structure of claim 11.
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Therefore the limitations of claim 11 are met by Kramer et al.
35 U.S.C. 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.
Claim(s) 1, 5-10, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Webber et al. (WO 2017/062622, international publication date: 04/13/2017).
Webber et al. (WO 2017/062622, international publication date: 04/13/2017) teach that “[t]he practice of medicine has been transformed by the use of biopharmaceuticals, with many drugs coming to market in recent years in the form of peptides and proteins (e.g., insulin, antibodies, cytokines)… These new classes of drugs have an array of attendant complications that arise from poor chemical and/or structural stability that can lead to the active drug being converted into an inactive and/or potentially immunogenic form… Extensive efforts have been devoted to the development of excipients for use in the formulation of biomolecules (e.g., proteins, antibodies) to confer improved stability… For example, excipients commonly used in the formulation of biomolecules include salts, sugars, amino acids, non-ionic surfactants, chelators, anti-microbial preservatives, carrier proteins, and polymers… An alternate approach to promote stability or modify pharmacological activity of drugs or other agents is through direct covalent modification. One of the most common modification strategies has been covalent attachment of poly(ethylene glycol) (PEG), which is intended to increase protein solubility, limit exposure to proteolytic enzymes or opsonins, increase the effective hydrodynamic size of the protein to reduce glomerular filtration, and/or inhibit protein aggregation… An alternative approach has relied on direct conjugation of zwitterionic polymers to fulfill similar objectives… An important issue with direct conjugation is ensuring site-specific modification away from the active site of the therapeutic in order to limit deleterious effects of the modification on protein function.” See [0003].
At [0004], Webber et al. teach that “[s]upramolecular chemistry, defined as ‘chemistry beyond the molecule,’ utilizes specific, directional, reversible, non-covalent molecular recognition motifs in order to achieve organization of molecules… Supramolecular host-guest motifs typically comprise a discrete macrocyclic host with a cavity that is selective for complimentary binding to certain guest ligands… In aqueous environments, several families of cyclic hosts, including cyclodextrins and cucurbiturils, select for inclusion of hydrophobic guests within their cavity… The affinity of a number of hydrophobic small molecule drugs with these hosts has been leveraged as a strategy to solubilize a wide variety of pharmaceutical compounds… Cucurbit[7]uril (CB[7]) has also been demonstrated to bind proteins with N-terminal aromatic amino acids (e.g., tryptophan and phenylalanine) through a combination of R-group inclusion within the cavity and electrostatic interactions between the protonated N-terminal amine and the carbonyl functionality on the CB[7] portal. For example, CB[7] can bind to insulin via its B1 phenylalanine residue…”
One of ordinary skill in the art would have been motivated with a reasonable expectation of success at the effective filing date of the invention to prepare a conjugate comprising a Zwitterion polymer, a linker (CB[7]), and a therapeutic peptide (insulin) in view of the teachings of Webber et al. One of ordinary skill in the art would have been motivated to do so, because Webber et al. teach that direct conjugation of therapeutic proteins, such as insulin, to zwitterionic polymers is a means of improving the stability of said therapeutic proteins. Furthermore Webber et al. suggest that said conjugation may be carried out via the use of CB[7], which binds to insulin. Based upon the teachings of Webber et al., one of ordinary skill in the art would have had ample motivation to prepare a conjugate comprising a Zwitterion polymer, a linker (CB[7]), and a therapeutic peptide (insulin), which could be used to treat individuals in need of insulin. The invention rendered obvious by the teachings of Webber et al. meets the limitations of claims 1, 5, 7, 9, and 12.
With respect to claim 6, according to [0004] of Webber et al., it appears that the CB[7] - insulin bond is non-covalent, with CB[7] binding to insulin via its B1 phenylalanine residue (amino group).
With respect to claims 8 and 10, given that the invention of Webber et al. meets the limitations of claims 1 and 9, both the invention of Webber et al. and the invention of the instant claims would be expected to demonstrate the same functional characteristics, such as a similar peak degree of polymerization and a similar in vivo half-life in humans.
Therefore the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention, as evidenced by Webber et al.
Claim(s) 2-4 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Webber et al. (WO 2017/062622, international publication date: 04/13/2017), as applied to claims 1, 5-10, and 12, and further in view of Webber et al. (WO 2017/062622, international publication date: 04/13/2017), Imamura et al. (ACS Omega, 4: 18234-18247, 2019), and Kramer et al. (Biomacromolecules, 13: 1719-1723, 2012, IDS).
As indicated above one of ordinary skill in the art would have been motivated with a reasonable expectation of success at the effective filing date of the invention to prepare a conjugate comprising a Zwitterion polymer, a linker (CB[7]), and a therapeutic peptide (insulin) in view of the teachings of Webber et al.
Weber et al. do not teach or suggest a zwitterionic poly (methionine sulfonium) copolymer, such as that recited in claims 2 and 3. This deficiency is remedied by Iwamura et al. and Kramer et al.
Similar to Webber et al., Imamura et al. teach the conjugation of therapeutic proteins to zwitterionic polymers, see the figure below:
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As indicated in the figure, conjugation of proteins to zwitterionic polymers, such as zwitterionic methionine sulfonium, has a stabilizing effect on the protein. At p. 18234, Imamura et al. teach that “[t]he past few decades have seen a significant interest in zwitterionic copolymers, owing to their unique and diverse features, especially their excellent protein resistance. These zwitterionic polymers contain oppositely charged ionic groups on the same molecule. Because of the structural similarity between the zwitterionic group and the cell membrane, zwitterionic polymers have also been employed as protein models and biointerfaces for medical, diagnostic, and biotechnological applications... Recently, a novel zwitterionic polymer containing tertiary sulfonium cationic groups has emerged, which can be regarded as one of the most promising candidates for various applications.”
Based upon the teachings of Iwamura et al., one of ordinary skill in the art would have been motivated to modify the conjugate of Webber et al. to comprise a zwitterionic poly (methionine sulfonium) copolymer, because there would have been a reasonable expectation that the resultant conjugate would be an effective and stable insulin delivery agent.
Kramer et al. teach “a new ‘click’ type reaction for polypeptide modification based on the chemoselective alkylation of thioether groups in methionine residues. The controlled synthesis of methionine polymers and their alkylation by a broad range of functional reagents to yield stable sulfonium derivatives are described. These ‘methionine click’ functionalizations are compatible with deprotection of other functional groups, use an inexpensive, natural amino acid that is readily polymerized and requires no protecting groups, and allow the introduction of a diverse range of functionality and reactive groups onto polypeptides.” See Abstract. At p. 1720, second column, Kramer et al. teach alkylation reactions that may be used to generate sulfonium derivatives of poly methionine. At the top of p. 1721, second column, Kramer et al. demonstrate a reaction that yields alkylated poly methionine, and the circled products of these reactions appear to meet the limitations of the structure of claim 11.
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At Figure 2, Kramer et al. teach that alkyl bromides comprising a carboxyl group may be reacted with poly methionine, and absent evidence to the contrary, the reaction result would produce the molecules recited in claims 2 and 3. Based upon the teachings of Iwamura et al., one of ordinary skill in the art would have been motivated to prepare a zwitterionic poly (methionine sulfonium) copolymer comprising the molecules recited in claims 2 and 3, because there would have been a reasonable expectation that the resultant conjugate would be an effective and stable insulin delivery agent. With respect to claim 4, it would be expected that the linkage between the molecules recited in claims 2 and 3 and CB[7] is a covalent linkage.
Therefore the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention, as evidenced by the references.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NELSON B MOSELEY II whose telephone number is (571)272-6221. The examiner can normally be reached on M-F, 9:00-6:00 EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis, can be reached at 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642
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