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 .
Priority
Acknowledgments are made that this application claims the priority to the following:
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Information Disclosure Statement
Files information disclosure statements (IDS) are 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 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.
I. Claims 1, 3-5 and 7-11 are rejected under 35 U.S.C. 103 as being unpatentable over Alagarsamy et al (US 8,580,918 B2) in view of Berge (Journal of Pharmaceutical Sciences, Jan 1977, Vol.66, No.1, 1-19; see applicants filed IDS dated 06/11/2024).
For claims 1, 3-5 and 7-9:
Alagarsamy teaches GLP-2 agonists including apraglutide peptides and their pharmaceutically acceptable salts [see claim 1].
Alagarsamy further teaches the sequence of apraglutide polypeptide [see SEQ ID NO:55], its synthesis and purification, wherein the purification process the fractions are pooled, and reloaded onto the column, wherein the purity of fractions are exceeding 93%, as determined by reverse-phase analytical HPLC and final fractions are washed with 5 volumes of 0.1 M ammonium acetate [See col.23, lines 13-36].
In the above teachings, SEQ ID NO:55 is identical to applicants apraglutide sequence and purity exceeding is interpreted as 93-100% pure, and impurities range from 0-7%. Also, before washing with ammonium acetate, wherein the fractions with purity exceeding 93%, is interpreted as apraglutide is 100% pure peptide, not in the salt form, and free from applicants claimed impurities.
So, Alagarsamy established the fact that first apraglutide was prepared as a free peptide and then it was modified into its salt form, which could be acetate and/or ammonium salts.
The difference between Alagarsamy et al and instant claims are as follows:
(i) Alagarsamy does not explicitly disclose the sodium salt of their peptide;
(ii) Alagarsamy also silent on recited impurities and their amounts in their disclosure.
With regard to (i) of above, though Alagarsamy teaches GLP-2 agonists including apraglutide peptides and their pharmaceutically acceptable salts [see claim 1], but silent on sodium salt form. However, sodium is the most common cation used in the pharmaceutical compounds or peptides. Moreover, it is cheaper cation and environment friendly compared to ammonium cation. Further, FDA provided list of approved pharmaceutically acceptable salts, both cations and anions, wherein the sodium was one of the cation [see Table 1 in Berge, Journal of Pharmaceutical Sciences, Jan 1977, Vol.66, No.1, 1-19]. Therefore, one would be motivated to replace ammonium salt in the teachings of Alagarsamy with sodium in view of economic/environmental reasons over the ammonium and also based in FDA recommendations.
With regard to (ii) of above, though the prior art silent on applicants cited impurities and their amounts, still the claims are obvious.
The reason is that the cited impurities must be originated either from the starting material or from the synthetic methodology. It appears that applicants are already acknowledged that origin of impurities in their specification [see section Impurities]. Regardless, applicants recited impurities are known or not, or whether applicants methodology for making the peptide is same or not to that of prior art, but the criticality or claimed subjected matter is limited to ‘purified product’, wherein the impurities are associated with the methodology and/or starting materials.
If applicants methodology is same or similar to that of prior art, then applicants cited impurities are expected.
If applicants methodology is not similar, claims are still obvious in view of the following case laws:
Purified compound over old and known compound is unpatentable. In re Mertz, 97 F. 2d 599, 38 USPQ 143(CPA 1938).
When claiming a purer form of a known compound, it must be demonstrated that the purified material possesses properties and utilities not possessed by the unpurified material. Ex parte Reed, 135 U.S.P.Q. 34, 36 (P.O.B.A. 1961), on reconsideration, Ex parte Reed, 135 U.S.P.Q. 105 (P.O.B.A. 1961). It has been well established that the mere purity of compound, in itself, does not render a substance unobvious Ex Parte Gray (BPAI 1989) 10 PQ2D 1922.
For claim 10:
Alagarsamy teach that after purification the fractions were pooled and lyophilized. [See col.23, lines 13-36].
For claim 11:
Alagarsamy further teaches synthesis and purification of apraglutide, wherein purification fractions are pooled, and finally the fractions are reloaded onto the column and washed with 5 volumes of 0.1 M ammonium acetate [See col.23, lines 13-36].
In the above, before washing with ammonium acetate, wherein the fractions with purity exceeding 93%, is interpreted as apraglutide is 100% pure and free from applicants claimed components.
Based on the above established facts from the cited prior art, it appears that all the claimed elements, i.e, applicants free form of apraglutide and also its salt forms, sodium is FDA approved cation, etc., 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.
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 product with a reasonable expectation of success. One would be motivated to take advantage of sodium, in view of cost effect and environmentally friendly element, compared to ammonium, and make sodium salt of apraglutide. Also, the motivation to apply teachings of 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.
II. Claims 1, 3-5 and 7-11 are rejected under 35 U.S.C. 103 as being unpatentable over Hargrove (J Pharmacol Exp Ther, May 2020, 373, 193-203; see applicants filed IDS dated 06/11/2024) in view of Berge (Journal of Pharmaceutical Sciences, Jan 1977, Vol.66, No.1, 1-19; see applicants filed IDS dated 06/11/2024) and Gaidhani (World Journal of Pharmaceutical Research, 2015, vol.4, issue 8, 516-543).
For claims 1, 3-5 and 7-11:
Hargrove teaches a synthesis of apraglutide, wherein the purity of peptide is greater than 90% [see section Peptide synthesis in page 194 and Table 1]. Hargrove further teaches that the peptide is dissolved in 0.1 N sodium hydroxide, to dissolve apraglutide at 10 mg free base/ml [see sub-section PK Studies in page 195]. Addition of sodium hydroxide is interpreted as formation of sodium salt which increases the solubility of the peptide.
In above, “the purity of peptide is greater than 90%” is interpreted as 90%-100% pure and so, the impurities range from 0-10%. Also, the apraglutide must be in the form of sodium salt, when the apraglutide reacts with sodium hydroxide. Therefore, the product obtained the teachings of Hargrove can be interpreted as sodium salt of apraglutide and impurities can range 0%-10%.
The difference between Hargrove and instant claims are as follows:
(i) Hargrove does not explicitly disclose the sodium salt of their peptide;
(ii) Hargrove silent on recited impurities in their peptides.
With regard to (i) of above, even if sodium salt form of apraglutide is absent in the teachings of Hargrove, but, the sodium is the most common cation used in the pharmaceutical compounds or peptides. It is cheaper cation and environment friendly compared to other cations, such as ammonium cation. Further, FDA provided the list of approved pharmaceutically acceptable salts, both cations and anions, wherein the sodium was one of the cation [see Table 1 in Berge, Journal of Pharmaceutical Sciences, Jan 1977, Vol.66, No.1, 1-19]. Therefore, one would be motivated to prepare sodium salt of apraglutide, in view of economic/environmental reasons over other salts.
With regard to (ii) of above, though the prior art silent on applicants cited impurities and their amounts, still the claims are obvious.
The reason is that the cited impurities must be originated either from the starting material or from the synthetic methodology. It appears that applicants are already acknowledged that origin of impurities in their specification [see section Impurities]. Regardless, applicants recited impurities are known or not, or whether applicants methodology for making the peptide is same or not to that of prior art, but the criticality or claimed subjected matter is limited to ‘purified product’, wherein the impurities are associated with the methodology and/or starting materials.
If applicants methodology is same or similar to that of prior art, then applicants cited impurities are expected.
If applicants methodology is not similar, claims are still obvious in view of the following case laws:
Purified compound over old and known compound is unpatentable. In re Mertz, 97 F. 2d 599, 38 USPQ 143(CPA 1938).
When claiming a purer form of a known compound, it must be demonstrated that the purified material possesses properties and utilities not possessed by the unpurified material. Ex parte Reed, 135 U.S.P.Q. 34, 36 (P.O.B.A. 1961), on reconsideration, Ex parte Reed, 135 U.S.P.Q. 105 (P.O.B.A. 1961). It has been well established that the mere purity of compound, in itself, does not render a substance unobvious Ex Parte Gray (BPAI 1989) 10 PQ2D 1922.
If applicants think removing the cited impurities are not easily achievable with known technology and a skilled person in the art cannot even envision it, then applicants need to state the facts in the form of declaration, which may overcome the rejection.
For claim 10:
Hargrove silent on lyophilized powder for the sodium salt of apraglutide. However, lyophilization of peptides or proteins and its advantages are well known in the art. For example, Gaidhani teaches that most proteins do not denature during the lyophilization process, and bacterial growth and enzyme action, which normally occur in aqueous preparations, can be eliminated. Thus, lyophilization ensures maximum retention of biological and chemical purity. [see page 522 and Conclusion in page 539]. Therefore, a skilled person in the art would be motivated to make lyophilized powder of apraglutide.
For claim 11:
Hargrove does not use salts of acetate or trifluoroacetic acid etc., in their peptide synthesis, and so, the apraglutide is expected to be free from these chemical components. Further, Hargrove teaches that “the purity of peptide is greater than 90%”, which is interpreted as 100% pure and so, the impurities can be 0%.
Based on the above established facts from the cited prior art, it appears that all the claimed elements, i.e, applicants free form of apraglutide and also its salt forms, sodium is FDA approved cation, etc., 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.
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 product with a reasonable expectation of success. One would be motivated to take advantage of sodium, in view of cost effect and environmentally friendly element, compared to ammonium, and make sodium salt of apraglutide. Also, the motivation to apply teachings of 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.
Nonstatutory Double Patenting Rejection
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 3-5 and 7-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7-9 and 16-17 of copending US 12,458,685B2 (corresponding US application number 17/462,908).
Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons:
Claims of present application are drawn to sodium salt of apraglutide having a purity of at least 97% and comprises with the recited amounts of impurities.
However, the recited open language “comprises” does not exclude other components in it. For example, it can include other possible impurities, as recited in the dependent claims, and can also have other components in it, such as amino acids [see 00203]. Accordingly, the claim is interpreted as a pharmaceutical composition.
Claims of US patent are drawn to (i) an aqueious pharmaceutical composition comprising sodium salt of apraglutide having purity of no less than 95%, and with the recited limitation and (ii) a method of treating short bowel syndrome by administering pharmaceutical composition of apraglutide.
In both cases, the product is common, which is apraglutide having the recited amounts of purity.
For claims 1, 3-5 and 7-9:
Claims of US patent teach the same product, which is apraglutide having purity of no less than 95%, which overlaps with the amount of purity of instant claims.
However, claims of US patent do not recite the impurities in it. The claim language says “comprising”, which does not exclude other components in the composition. According to the specification of US patent, its definition includes impurities in the composition, such as beta-Asp3 and D-His [see Summary of Invention]. So, the composition of copending application also comprises same impurities in it.
For claim 10:
Claims of US patent silent on lyophilized peptide. However, specification defined that apraglutide is lyophilized and formulated into a drug product. [see col.22, lines 10-13].
For claim 11:
Claims of US patent silent on the recited component in their composition. However, specification defined that their composition is free from acetate, trifluoroacetic acid, acetonitrile, bacterial endotoxins, aerobic microbes, yeasts, mold, or any combination thereof. [see col.22, lines 6-9].
The above differences, however, do not constitute a patentable distinct, because of overlap of the scope of subject matter, in the claims of US patent and instant claims, and therefore obvious.
Conclusion
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SUDHAKAR KATAKAM
Primary Examiner
Art Unit 1658
/SUDHAKAR KATAKAM/Primary Examiner, Art Unit 1658
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