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 .
Claim 2 has been cancelled. Claims 17-19 were introduced by amendment on 3/27/2024.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed.
Applicant cannot rely upon the certified copy of the foreign priority application for benefit of the priority date because this document in not in English. The effective filing date for the instant application is 12 May 2022.
Specification/Sequence Listing
The substitute specification filed 4/29/2024 has not been entered because it does not conform to 37 CFR 1.125(b) and (c).
The clean copy still contains markings. See at least pages 11-13.
The substitute sequence listing submitted 4/29/2024 is acknowledged.
SEQ ID NO: 24 in the sequence listing is a skipped sequence. SEQ ID NO: 24 corresponds to FFG. See claim 7. This sequence identifier should not appear in the specification. See paragraph [0033] of the specification.
The disclosure is objected to because of the following informalities:
The incorporation of sequence listing on page 1 of the specification should reference the size of the file in bytes not kilobytes (KB). See MPEP 2422.03(I).
The sequences disclosed on pages 5 and 16 do not reference the corresponding sequence identifiers.
The sequence disclosed on pages 18 and 35 (RRRRRRRR) does not reference the corresponding sequence identifier and does not appear to be present in the sequence listing.
The sequence disclosed on page 19 for the amino acid sequence of PA-CPP-GLP-2 (FFLIPKGRRRRRRRRGGHADGSFSDEMNTILDNLAARDFINWLIQTKITDC) does not reference the corresponding sequence identifier and does not appear to be present in the sequence listing.
The application has Figures 1-5, 6A-B, 7A-C, 8-12, 13A-B, and 14. However, Figure 7A has subparts A and B and Figure 7B has subparts A and B. This is confusing and these subparts of Figure 7A and Figure 7B are not described in the brief description of the drawings. See pages 6-7 of the specification.
Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 16 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because claim 16 recites a use of a pharmaceutical composition with no positive, active steps for said use. See MPEP 2173.05(q).
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 17-19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for methods as set forth below, does not reasonably provide enablement for all methods encompassed by the claims. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Claims 17-19 are directed to therapeutic methods. The claims do not administer a therapeutically effective amount of the glycosylated neuropeptide derivative to the patient. The claims do not require any particular therapeutic effect. In the absence of a more specific limitation, all therapeutic effects must be enabled.
The specification defines “treatment” as referring not only to an activity or an effect that quenches or alleviates a symptom, but also to an activity or an effect that suppresses aggravation of the symptom.
In view of the specification disclosure, the claims are considered to include amelioration and cure of all neuropsychiatric disorders and neurodegenerative disorders, including amelioration of the underlying causes and all symptoms/characteristics of the disorders.
The specification discloses PAS-CPP-GLP-2 (11-sugar), PAS-CPP-GLP-2 (5-sugar), PAS-CPP-GLP-2 (no sugar) on page 19 of the specification.
Note that Figures 2-3, 10-11, and 13A-B show statistically significant results between administering vehicle (such as PBS) as compared to the unglycosylated neuropeptide or the glycosylated neuropeptide. However, no statistically significant results are shown between administration of the neuropeptide and the glycosylated neuropeptide.
The GLP-2 embodiments with sugar chains attached were more soluble in PBS (i.e. aqueous solution). Note that not all neuropeptides (such as GLP-1) have issues with aqueous solubility. See for examples, page 32, line 1, of the specification.
These GLP-2 derivatives were tested by administering to mice who then perform a forced swim test. The mice receiving GLP-2 derivatives with sugar chains attached had a shortened immobility time. The specification states that the forced swim test leads to a depression-like state in the mice.
These GLP-2 derivatives were tested in an LPS-induced amnesia model (Y-shaped maze) in mice. The specification states that the mice receiving GLP-2 derivatives with sugar chains attached had better learning/memory functions.
These examples and the limited constructs encompassed by the claims do not enable the methods of treatment claimed. They do not speak to amelioration or cure, including all symptoms/characteristics of the disorders. At least for example, there is no evidence of record or reason to believe that administration of any claimed glycosylated neuropeptide derivative would cure Alzheimer’s disease or amyotrophic lateral sclerosis (ALS, a neurodegenerative disease). There is no evidence of record or reason to believe at administration of any claimed glycosylated neuropeptide derivative would ameliorate cognitive loss or lost motor function in these conditions. At least for example, there is no evidence of record or reason to believe that administration of any claimed glycosylated neuropeptide derivative would address underlying causes of any of these diseases when in many cases they are not known.
These results cannot be extended to other neuropeptides with highly variable structure amino acid structures and biological functions or to other methods of administration such as topical, oral, or subcutaneous administration or to other sugar structures (in number, type, and arrangement). Note that claims 17 and 19 do not require intranasal administration. Note that the claims do not require any particular monosaccharide type or arrangement of the 5-20 monosaccharide residues in the sugar chain.
The scope of the claims is 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 7, 8, 13, and 16 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 7 is indefinite in failing to recite sequence identifiers for the recited sequences.
Claim 8 is indefinite as the word processing for the 3/27/2024 amendment deleted the claim number. Correction is required. In addition, the claim is confusing in reciting that the sugar chain binds to the neuropeptide sequence via c cysteine residue or an asparagine residue. The sugar chain doesn’t bind to the neuropeptide. It is attached to the neuropeptide through a chemical reaction.
The preamble of claim 13 is directed to an intranasal/nasal drop formulation; however, the body of the claim requires nothing more than the glycosylated neuropeptide derivative according to claim 1. This is confusing. The claim could be restructured to recite a “pharmaceutical composition comprising the glycosylated neuropeptide derivative according to claim 1 in an intranasal/nasal drop formulation.” This would clearly distinguish the products.
Claim 16 is directed to a use without any positive, active steps for said use. The claim is indefinite. See MPEP 2173.05(q).
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 10-12 and 14-16 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 10 does not further limit the subject matter of claim 1 as it requires nothing more than the glycosylated neuropeptide derivative of claim 1. Claims 11-12 do not further limit the subject matter of claim 10 as an intended use “i.e. used for therapy of…” does not further limit the claimed product. Claims 14-15 do not further limit the subject matter of claim 13 as an intended use “i.e. used for therapy of…” does not further limit the claimed product. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
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 and 3-19 are rejected under 35 U.S.C. 103 as being unpatentable over Yamashita et al. (U.S. Patent Application Publication 2017/0253643, of record) in view of Kajihara et al. (U.S. Patent Application Publication 2009/0111739).
Yamashita et al. (U.S. Patent No. 2017/0253643, of record) discloses many neuropeptides such as GLP-1. See at least paragraph [0059] and claim 3. Neuropeptides having a neuropeptide sequence, a cell-penetration accelerating sequence, and an endosomal-escape accelerating sequence are disclosed. See at least claims, particularly claim 15, for endosomal-escape accelerating sequence of FFLIPKG, LILIG, FFG, FFFFG, and FFFFFFG. Intranasal formulations and intranasal administration is disclosed. Nasal formulations and administration of these formulations are disclosed. See at least claims 10-13. Administration to treat conditions such as depression and a neuropsychiatric disorder are disclosed. See at least claims 6 and 8. GLP-1 and other disclosed neuropeptides are less than 200 amino acids. See instant claim 4. The cell-penetrating sequences are disclosed. For example, SEQ ID NO: 26 is KKKKKKKKK (cationic, basic amino acids). See at least paragraphs [0070-0072 and 0076] and the position of the elements are disclosed in paragraph [0075]. See instant claims 5-6 and 9.
Kajihara et al. (U.S. Patent Application Publication No. 2009/0111739) discloses adding five or more monosaccharide sugars to Glp-1 through an added cysteine to improve stability. See at least abstract and paragraphs [0095-0096, 0178, 0183-0185].
It would have been obvious to glycosylate the GLP-1 constructs of Yamashita et al. according to the method of Kajihara et al. to improve its stability.
With respect to claims 10, only the glycosylated neuropeptide derivative suggested by Yamashita et al. and Kajihara et al is required. With respect to claims 11-12, nothing more than the glycosylated neuropeptide derivative is required. The limitations “used for therapy of neuropsychiatric disorder or a neurodegenerative disease” and “used for therapy of depression or dementia” are intended uses and do not further define the claimed product. With respect to claims 14-15, nothing more than the intranasal/nasal drop formulation of claim 13 suggested by Yamashita et al. and Kajihara et al is required. The limitations “used for therapy of neuropsychiatric disorder or a neurodegenerative disease” and “used for therapy of depression or dementia” are intended uses and do not further define the claimed product. Claims 16-19 require nothing more than administration to a subject. The intranasal administration to a subject. The product is suggested by Yamashita et al. and Kajihara et al. and intranasal administration is suggested by Yamashita et al. Treatment of conditions such as depression and neuropsychiatric disorders (see instant claims 17-19) are disclosed.
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama can be reached at 571-272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Marianne P Allen/Primary Examiner, Art Unit 1647
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