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
Filed information disclosure statements (IDS) 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.
Response to Restriction
Applicant's response to restriction requirement and election of group I corresponding to claims 2-4, 6, 8-15, 17-19, and 23-25, without traverse, in the reply filed on 05/19/2026 is acknowledged.
The examiner also acknowledges applicants response to election of species and providing following species for the claimed variables:
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Elected group and its corresponding elected species are examined in this office action.
Claims 26-27 are withdrawn from consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
The claims 2-4, 6, 8-15, 17-19, and 23-25 are examined on merits in this office action.
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.
Claims 2-4, 6, 8-15, 17-19, and 23-25 are rejected under 35 U.S.C. 103 as being unpatentable over Norona (Blood, 17 Sep 2020, vol.136, No.12, 1442-1455; see applicants filed IDS dated 12/01/2023) in view of Hargrove (Journal of Pharmacology and Experimental Therapeutics, May 2020, 373, 193-203; see applicants filed IDS dated 12/01/2023), Anonymous (Apraglutide Receives Orpha Drug Designation for Short Bowel Syndrome, Jan 05, 2019; see applicants filed IDS dated 12/01/2023) and Berge (Journal of Pharmaceutical Sciences, Jan 1977, Vol.66, No.1, 1-19).
For claims 2-4 and 6:
Norona teaches treating acute-graft-versus-host disease (GVHD), including gastrointestinal and steroid refractory or steroid-naïve, by administering GLP-2, such as teduglutide, in mice and humans. [see abstract, Figures and Discussion].
Difference is that Norona is silent on applicants claimed apraglutide.
However, the following art teaches advantages of apraglutide over other GLP-2 analogs:
Hargrove teaches that apraglutide offers several advantages over existing GLP-2 analogs and is an excellent candidate for the treatment of gastrointestinal diseases, such as SBS [see abstract].
Anonymous teaches that apraglutide (FE 203799) – a next-generation, synthetic GLP-2 analog – has demonstrated a superior pharmacokinetic profile with a half-life of 30 hours across multiple phase 1 single ascending dose/multiple ascending dose clinical trials in healthy volunteers, according to the release [see abstract].
Therefore, one would be motivated to replace teduglutide in the teachings of Norona and arrive at applicants claimed method with a reasonable expectation of success, in light advantages of apraglutide and guidance provided to treat GVHD in the teachings of Norona.
For claim 8:
Norona teaches MAGIC guidelines on GVHD diagnosis, staging and treatment etc. [see section Human Data in Materials and Methods].
For claims 9-15:
Norona teaches that lower intestinal GLP-2 levels are observed in GVHD and TBI or chemotherapy and patients often receive chemotherapy prior to transplantation. So, it appears that chemotherapy lowers GLP-2 levels and lower levels of GLP-2 trigger GVHD. [See section GVHD after TBI or chemotherapy depletes L cells and its product GLP-2; and Fig.1]
Based on above, it is advisable to administer GLP-2 analog ahead of time to delay or treat expected deficiency of GLP-2, since lower levels trigger GVHD.
Therefore, a skilled person in the art would be motivated to administer GLP-2 analog prior concurrently to the subject being administered transplant or radiation or chemotherapy.
For claim 17:
Norona silent on sodium salt form of GLP-2. However, Hargrove teaches that apraglutide is dissolved in sodium hydroxide [see section Preparation of Dosing Solutions in page 195-196], and so it should results in sodium salt of apraglutide, absent evidence to the contrary.
Even if Hargrove does not teach apraglutide in sodium salt form, still this limitation is obvious because sodium is the most common cation used in the pharmaceutical compounds or peptides. Moreover, it is cheaper cation and environment friendly. 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 et al, Journal of Pharmaceutical Sciences, Jan 1977, Vol.66, No.1, 1-19]. Therefore, one would be motivated to make sodium salt of apraglutide.
For claim 18:
Though Norona silent on subcutaneous administration, however, subcutaneous administration of apraglutide is known in the art. For example, Hargrove teach administration of apraglutide via intravenous and subcutaneous [see abstract].
For claims 19 and 23:
It appears that Norona silent on applicants claimed concentration range. However, Hargrove teaches various doses, for example, 5 mg/kg apraglutide [see section Preparation of Dosing Solutions in page 195], and 0.025-0.2 mg/kg [see Fig.2], 0.5-12 mg/kg [see third paragraph in right column in page 199].
Generally, differences in concentrations of components of a formulation will not support the patentability of subject matter encompassed by the prior art. Such formulations are results-effective variables which can be optimized. In in re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980), it was held that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Further, in In re Aller, 220 F. 2d454, 456, 105 USPQ 233,235 (CCPA 1955) the courts maintained that: "Where the general condition of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." As formulating optimal compositions for medicaments is routine in the art of pharmacology, the claims are considered to be prima facie obvious.
For claim 25:
See For claims 2-4 and 6 above.
For claim 26:
Norona teaches prednisolone treatment [see Fig.2].
Based on the above established facts from the cited prior art, it appears that all the claimed elements, i.e, applicants individual components in the composition and their use in treating GVHD, 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.
A combination of prior art references is only proper if a person of ordinary skill in the art at the time of the invention, faced with the same problem, would have been motivated to combine their teachings with a reasonable expectation of success. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007). Here, the technical fields and problems addressed by the references are not distinct from that of the present invention.
So, the motivation to combine the 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. 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 method with a reasonable expectation of success.
The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art or drawn from a convincing line of reasoning based on established scientific principles or legal precedent, that some advantage or expected beneficial result would have been produced by their combination. In re Sernaker, 702 F.2d 989, 994-95, 217 USPQ 1, 5-6 (Fed. Cir. 1983).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUDHAKAR KATAKAM whose telephone number is (571)272-9929. The examiner can normally be reached 8:30 am to 5 pm.
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SUDHAKAR KATAKAM
Primary Examiner
Art Unit 1658
/SUDHAKAR KATAKAM/Primary Examiner, Art Unit 1658
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