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 Claims
Claims 1-2, 4, 8-9, 24, 27, 29, 32-33, 39-41, 43-44, 48-50, 54 and 60 are pending in the instant application and subject to examination herein.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/03/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112(b)
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.
Claim 48 is 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 48 further limits claim 1, regarding a genus of 4-hydroxypyrrolidinyl ester compounds designated as instant Formula (I), to wherein the compound of Formula (I) “is selected from those in Table 1A and Table 1B, and pharmaceutically acceptable salts thereof”. Claim 48 does not include any “Table 1A” or “Table 1B”, although the instant Specification does include tables that are titled as “Table 1A” and “Table 1B”. Claim 48 is indefinite because the claim is not complete in itself, and does not include the identification of the compound(s) being claimed. Given that claim 48 is drawn to a compound or set of compounds, there is no apparent necessity in identifying the compounds by reference to table(s) of the instant disclosure, because the compounds can be readily represented by name or structure within the claim. Applicant is referred to MPEP § 2173.05(s), included below:
Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted)
Claim Rejections - 35 USC § 102
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, 4, 24, 27, 29, 39-41, 43-44, 49 and 60 are anticipated by Zhang.
Claims 1-2, 4, 24, 27, 29, 39-41, 43-44, 49 and 60 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Zhang (US PG Pub 2023/0365498 A1).
Claim 1 is drawn to a genus of 4-hydroxypyrrolidinyl ester compounds, designated as instant Formula (I), including substituents R1-R5a/b and additional limitations and shown in the table below. Zhang discloses the synthesis of a series of derivatives of the known compound anisomycin1, shown in the table below, as well as the utility of anisomycin and its derivatives as agonists of glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) (Abstract):
Claim Number(s) of Instant Application
Instant Application
Zhang
1
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192
372
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wherein:
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192
306
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Anisomycin (paragraph [0007])
Thus, claim 1 is anticipated by the disclosure of Zhang.
Claims 2, 4, 24, 27, 29, 39-41 and 43-44 further limit claim 1, each to a narrower genus of compounds, and each is anticipated by the compound anisomycin shown in the table above. Claim 29, in particular, requires that at least one instance of the group “Y” is CH2, -O-, or N(R1a)-; however, claim 29 does not require that a single instance of “Y” is present in the structure.
Claim 49 further limits claim 1 to a composition comprising the compound of claim 1, or a pharmaceutically acceptable salt thereof, and an excipient. Zhang provides a pharmaceutical composition including at least one of anisomycin, anisomycin derivatives disclosed therein, or pharmaceutically acceptable salts, solvates and stereoisomers thereof as active ingredient, and can further include excipients (paragraphs [0025] and [0027]).
Claim 60 further limits claim 1 to a method of modulating protein synthesis in a subject in need thereof or in a cell, tissue, or biological sample, comprising administering to the subject in need thereof or contacting the cell, tissue, or biological sample with an effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof. Zhang discloses a method to treat or prevent diabetes, including administering an effective dosage of at least one of anisomycin or a derivative of anisomycin disclosed therein , or salts or solvates thereof (paragraphs [0029]-[0030]).
Thus, claims 2, 4, 24, 27, 29, 39-41, 43-44, 48 and 60 are anticipated by the disclosure of Zhang.
Claims 1-2, 4, 8-9, 24, 27, 29, 39-41, 43-44, and 48 are anticipated by Schwardt.
Claims 1-2, 4, 8-9, 24, 27, 29, 39-41, 43-44, and 48 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Schwardt (Schwardt, et al.; Synthesis, pp1473-1490; 1999).
The limitations of claims 1-2, 4, 24, 27, 29, 39-41 and 43-44 and the structure of anisomycin are disclosed in the rejection above and hereby incorporated into the instant rejection.
Schwardt teaches a study in the synthesis and cytotoxic activity of a series of optically active cyclic amino alcohols, including the known anti-pathogenic agent anisomycin, designated by Schwardt as compound 1, and shown in the table in the rejection above.
Thus, claims 1-2, 4, 24, 27, 29, 39-41 and 43-44 are anticipated by the teaching of Schwardt.
Claim 8 further limits the genus of compounds of claim 1, to wherein the R1 substituent is selected from a Markush group of named substituents, including phenyl.
Claim 9 limits the genus of compounds of claim 1, to wherein the R1 substituent is selected from a Markush group of substituents presented by structure, including phenyl.
Schwardt teaches an anisomycin salt derivative, designated by Schwardt as compound 19,2 shown in the table below, wherein the acetyl group of anisomycin is replaced with a benzoyl group, thereby combining R1 and R2 of instant Formula (I) into a phenyl group, and further wherein the p-methoxyphenyl ring at R3 is replaced with phenyl:
Claim Number(s) of Instant Application
Instant Application
Schwardt
8, 9
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192
372
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wherein:
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238
256
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Compound 19
Thus, claims 8-9 are anticipated by the teaching of Schwardt.
Claim 48 further limits claim 1 to a Markush group of specific compounds identified in the instant disclosure within Tables 1A and 1B. Schwardt discloses compound, designated as compound 18,3 shown in the table below, that is a hydrochloride salt of a compound found in instant Table 1A (page 123, uppermost compound in right column):
Claim Number(s) of Instant Application
Instant Application
Schwardt
8, 9
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192
372
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wherein:
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254
270
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Compound 18
Thus, claim 48 are anticipated by the teaching of Schwardt.
Claims 1-2, 4, 24, 27, 29, 39-41, 43-44, 48, 50 and 54 are anticipated by Grollman.
Claims 1-2, 4, 24, 27, 29, 39-41, 43-44, 48, 50 and 54 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Grollman (Grollman, A. P.; The Journal of Biological Chemistry, v242, pp3226-3233; 1967).
The limitations of claims 1-2, 4, 24, 27, 29, 39-41, 43-44 and 48 are discussed in the rejections above and hereby incorporated into the instant rejection. The structure of anisomycin and the claims met by the structure of anisomycin are discussed in the rejections above and hereby incorporated into the instant rejection.
Grollman teaches a study on the mechanism of protein synthesis inhibition of anisomycin in HeLa cells, rabbit reticulocytes, Saccharomyces fragilis, and cell-free extracts prepared from these sources (Abstract, page 3226). Grollman does not illustrate the structure of anisomycin but does provide the structure-interpretable IUPAC name.4
Thus, claims 1-2, 4, 24, 27, 29, 39-41 and 43-44 are anticipated by Grollman.
In addition to anisomycin, Grollman teaches a family of anisomycin derivatives, including Grollman’s compound IV,5 which is found in Table 1A of the instant Specification (page 124, right column, second row) and shown below, and thereby meets the limitation of claim 48.
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156
242
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(Grollman’s compound IV)
Thus, claim 48 is anticipated by the teaching of Grollman.
Claim 50 further limits claim 1 to a method of modulating protein synthesis in a subject in need thereof or in a cell, tissue, or biological sample, comprising administering to the subject in need thereof or contacting the cell, tissue, or biological sample with an effective amount of the compound of claim 1 or a pharmaceutically acceptable thereof.
Claim 54 further limits claim 1 to a method of decreasing protein synthesis in a subject in need thereof or in a cell, tissue, or biological sample, comprising administering to the subject in need thereof or contacting the cell, tissue, or biological sample with an effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof.
As discussed above, Grollman teaches that anisomycin inhibits protein synthesis in HeLa cells, rabbit reticulocytes, Saccharomyces fragilis, and cell-free extracts prepared from these sources. Grollman further teaches that partial inhibition of deoxyribonucleic acid synthesis in HeLa cells is observed at anisomycin concentrations which produce 95% inhibition of protein synthesis. These effects on protein and DNA synthesis are rapid in onset and reversible. Anisomycin acts on the transfer reaction subsequent to the formation of aminoacyl transfer ribonucleic acid. In the presence of anisomycin, nascent peptide remains attached to polyribosomes (Abstract, page 3226).
Thus, claims 50 and 54 are anticipated by the teaching of Grollman.
Claims 1-2, 4, 24, 27, 29, 39-41, 43-44 and 48 are anticipated by PubChem.
Claims 1-2, 4, 24, 27, 29, 39-41, 43-44 and 48 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by PubChem (PubChem CID 139583092, created 04Nov2019)6.
The limitations of claims 1-2, 4, 24, 27, 29, 39-41 and 43-44 are discussed in the rejections above and hereby incorporated into the instant rejection.
PubChem discloses a compound7 within scope of instant Formula (I), as claimed in claim 1, as shown in the table below:
Claim Number(s) of Instant Application
Instant Application
PubChem CID 139583092
1
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192
372
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wherein:
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216
304
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Greyscale
Thus, claim 1 is anticipated by the disclosure of PubChem.
Claims 2, 4, 24, 27, 29, 39-41 and 43-44 further limit claim 1, each to a narrower genus of compounds, and each is anticipated by the compound shown in the table above. Additionally, regarding claim 48, the compound disclosed by PubChem is found in the instant disclosure in Table 1A (page 133, right column, second compound from bottom).
Thus, claims 2, 4, 24, 27, 29, 39-41, 43-44 and 48 are anticipated by the disclosure of PubChem.
Allowable Subject Matter
Claims 32-33 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to W. JUSTIN YOUNGBLOOD whose telephone number is (703)756-5979. The examiner can normally be reached on Monday-Thursday from 8am to 5pm. The examiner can also be reached on alternate Fridays.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey S. Lundgren, can be reached at telephone number (571) 272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/W.J.Y./Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
1 (2R,3S,4S)-4-Hydroxy-2-[(4-methoxyphenyl)methyl]pyrrolidin-3-yl acetate
2 3,4-Pyrrolidinediol, 2-(phenylmethyl)-, 3-benzoate, hydrochloride (1:1), (2R,3S,4S)
3 3,4-Pyrrolidinediol, 2-(phenylmethyl)-, 3-acetate, hydrochloride, (2R,3S,4S)
4 2-p-methoxyphenylmethyl-3-acetoxy-4-hydroxypyrrolidine
5 (2R,3S,4S)-2-[(3-bromo-4-methoxyphenyl)methyl]-4-hydroxypyrrolidin-3-yl acetate
6 Cited in Applicant’s Information Disclosure Statement dated 02/03/2025.
7 (2R,3S,4S)-4-hydroxy-2-[(4-methoxyphenyl)methyl]pyrrolidin-3-yl propanoate
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