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 .
Election/Restrictions
Applicant’s election without traverse of Group I and the species of immunoglobulins as the protein and peptide blockers in the reply filed on 9/30/2025 and the more particular peptide blocker species of CE3 (SEQ ID NO: 1) on 4/27/2026 is acknowledged.
Upon further consideration of the claims, the species election for the protein and the blocking group have been withdrawn.
Claims 17-35 and 52-70 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 9/30/2025.
Specification
The sequence listing submitted 4/27/2026 is acknowledged.
The substitute specification filed 4/27/2026 has not been entered because it does not conform to 37 CFR 1.125(b) and (c). The substitute specification filed 4/27/2026 (clean and marked copies) included the original abstract and the original claims. These should not have been included. Only the description portion with the corrections (additions/deletions) should have been presented. Correction is required.
Claim Objections
Applicant is advised that should claims 1-2 and 4-16 be found allowable, claims 36-37 and 39-51 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claims 36-37 and 39-51, respectively, have the same limitations as claims 1-2 and 4-16, respectively, except for the term “reversibly” in the preamble of claim 1 which is not present in the preamble of claim 36. However, both claims 1 and 36 require that “at least one of the first bond and the second bond is cleavable.” As such, both sets of claims reversibly prevent a protein from interacting with a second protein.
Claims 4 and 39 are objected to because of the following informalities: The term “stearic” is misspelled. It should be “steric.” Appropriate correction is required.
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 1-16 and 36-51 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 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, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1 and 36 are directed to generic blocking groups that must reversibly prevent interaction with a second protein due to steric or electrostatic interference.
With respect to claims 3 and 38, only glucagon is disclosed as forming fibrils and only insulin is disclosed as forming hexamers. Immunoglobulins (see claims 8 and 38) are not disclosed as forming fibrils or hexamers. No other protein-protein complexes forming fibrils or hexamers are described.
The specification discloses linking the protein glucagon to the blocking group CEn for each of n=1-5 using activated PDE as the linking moiety. No other blocking groups are disclosed and the CEn where n=1-5 are not tested for the required functions. They are not disclosed as having these properties. The CEn blocking groups do not adequately describe all blocking groups having the structures and functions required by the claims. No reasonable structure-function correlation has been established that is commensurate in scope with the claims. The specification does not describe representative examples to support the claims.
In particular, claims 6 and 41 recite that the blocking group comprises a peptide, lipid, small molecule, nucleic acid, saccharide or combinations thereof. The specification does not disclose any blocking groups that are formed from combinations of any subset or all of the recited molecules (e.g. a blocking group that contains a peptide, a nucleic acid, and a saccharide).
The CEn blocking groups where n is 1-5 are insufficient to describe all blocking groups having the numerous combinations embraced by the claims. In particular, it is unknown which of the numerous blocking structures encompassed would have the activity of preventing interaction with a second protein due to steric or electrostatic interference.
The blocking groups of the claims are not adequately described.
Claims 1-16 and 36-51 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The specification discloses linking the protein glucagon to the blocking group CEn for each of n=1-5 using activated PDE as the linking moiety. See at least Figures 5, 7, 9, 11, 13, and 15 and Example 1. No other blocking groups, no other linking moiety, and no other proteins are exemplified. The specification does not disclose that that constructs prevent the protein from interacting with a second protein. For example, there are no experimental results demonstrating that glucagon-PDE-CE does not form a fibril with other glucagon proteins or does not bind to the glucagon receptor. (See page 1 of the specification.) There is no disclosure or evidence of record that any steric or electrostatic interference occurs. (See instant claims 1-2, 4-5, 36-37, and 39-40.) Note that the specification does not identify the particular amino acid(s) in glucagon where the linking moiety is attached. The claims do not require that the linking moiety be attached to any particular amino acid in the protein. Note that the claims are not limited to preventing self-aggregation of a protein as in instant Figures 1 and 2. Note that the first protein and second protein are not required to be the same protein.
The specification makes molecules having structures embraced by the claims but does not establish that they possess the required functions of the claims.
One of ordinary skill in the art would not have been able to extrapolate or predict these functional results for glucagon-PDE-CEn where n=1-5.
No functional results could be extrapolated or predicted for other proteins (e.g. insulin or immunoglobulins), other linking moieties, or other structurally undefined blocking groups encompassed by the claims. It would constitute undue experimentation to determine those protein blocking assemblies having the structure and function encompassed by the claims. The structural variability is large, there are no working examples, and those of ordinary skill in the art would not have been aware of similar protein blocking assemblies having similar structure and function.
Chintala et al. (2025) was published well after the effective filing date of the instant application and demonstrates that glucagon-CE3 and glucagon-CK3 were resistant to fibril formation but that use of other peptides such as CQ3, CG3, CA3 were not. See at least abstract and Figures 1, 7, and 9. Note that this information would not have been available to those of ordinary skill in the art at the time of the invention. The claims must be enabled at the time of invention.
The claims are not enabled.
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 1-16 and 36-51 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.
Claims 1 and 36 recite “static interference.” It is unknown what this means. It appears that it might be an error and that “electrostatic interference” was intended. See dependent claims 5 and 40. Note that claims 5 and 40 lack antecedent basis for “electrostatic” in claims 1 and 36, respectively.
Claims 3 and 38 lack antecedent basis in claims 1 and 36, respectively, for “protein-protein complexes.”
Claims 5 and 40 are confusing reciting “charge, partial charge, or combinations thereof.” It is unclear what a “combination” would be as the complete charge would include the partial charge. Clarification is requested.
Claims 7 and 42 are confusing in reciting Cen, where n=1-5 and referencing them as SEQ ID NOS: 1-3. SEQ ID NOS: 1-3 refer only to where n is 3, 4, or 5, respectively. The peptides where n=1-5 are CE, CEE, CEEE (SEQ ID NO: 1), CEEEE (SEQ ID NO: 2), and CEEEEE (SEQ ID NO: 5). These claims are confusing as written.
Claims 8 and 43 are confusing in reciting the protein is selected from the group consisting of insulin, glucagon, immunoglobulin, their derivatives or analogs and combinations thereof.” It is unclear if the protein referred to is the protein in the protein blocking assembly or is the second protein. It is unclear what the structure of a protein that is a “combination” of those listed would be with respect to the protein blocking assembly or how a protein that is a combination such as a combination of insulin and glucagon would be assembled with respect to the protein blocking assembly. The specification does not provide the metes and bounds with respect to derivatives or analogs, particularly for immunoglobulins. Clarification is requested.
Claims 10 and 45 are confusing in reciting “functional group is of the protein selected from the group consisting of amine, alcohol…” This phrase does not make sense grammatically and appears to be an error.
Claims 16 and 51 are confusing in reciting that “at least one of the first and second bond comprises one or more esters, amides…” A bond is a single chemical connection between two atoms (i.e. a bond between carbon (C) and hydrogen (H), C-H). For example, methane, CH4 contains four separate and distinct C-H bonds. The recitation “one or more” implies multiple bonds. By comparison, a linking moiety could contain multiple esters, amides, etc. The claims are confusing.
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.
Claims 1-2, 4, 9-13, 16, 36-37, 39, 44-48, and 51 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Filpula et al. (of record).
Filpula et al. teaches a therapeutic protein conjugated to polyethylene glycol (PEG) via a releasable linker. The PEG blocks the therapeutic protein from interaction with its biological protein target (i.e. second protein) through steric interference. When the releasable linker is activated, the therapeutic protein is free to interact with its protein target. See at least abstract, Figure 3, section 1.2, and section 2. The PEG can be attached to a surface lysine amine of the protein. See instant claims 9-10 and 44-45. Hydrolysis of an ester bond to release the protein in plasma (i.e. endogenous in human or animal body) is disclosed. See Figure 4 and instant claims 11-13, 16, 46-48, and 51.
The prior art of record and not relied upon is considered pertinent to applicant's disclosure.
Adams et al. (WO 2019/115674, of record) was cited on the search report. It teaches an antibody against alpha synuclein where the antibody can be conjugated to PEG with a cleavable linker. The antibody can prevent aggregation of alpha synuclein induced by alpha synuclein fibrils. Adams et al. does not teach the protein blocking assembly of the instant claims. The reference does not teach a first protein linked to a linking moiety where the linking moiety is also linked to a blocking group that prevents interaction of the first protein with a second protein.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIANNE P ALLEN whose telephone number is (571)272-0712. The examiner can normally be reached 7:00-3:30 EST Monday-Friday.
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/Marianne P Allen/Primary Examiner, Art Unit 1647
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