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 application
Receipt of applicant’s remarks and claim amendments filed on 08/14/2025 are acknowledged.
However, applicants’ arguments for previous only pending 103 rejection are found not persuasive. Accordingly, the rejection is maintained and modified to address claim amendments. Please see the examiners response to applicants below.
Response to Arguments
Applicants’ argue that none of the secondary documents Karsdal, Chaudhari, Lee or Ernbury point towards the use of the absorption enhancers according to the amended claim 1 in combination with compound A, or even a compound remotely similar to compound A. The person of ordinary skill would not be motivated to select the absorption enhancers found in the cited references and would have no reasonable expectation of success in applying the said absorption enhancers for present compound A.
Though the rejection provided the reasoning for advantages of absorption enhancers, but it appears that applicants fail to explain ‘why the combination of compound A with absorption enhancer’ does not work.
Applicants further argue that as described in the specification, the claimed oral pharmaceutical compositions significantly improve the oral bioavailability of compound A.
As explained in the rejection, Karsdal teaches that the obstacles in oral formulations can be overcame with various strategies to increase bioavailability of proteins and peptides, and suggests introducing ‘absorption enhancers’ in the peptide formulations. Therefore, improvement in bioavailability is expected when the compound A is combined with absorption enhancer, absent evidence to the contrary.
Claim Rejections - 35 USC § 103 [Maintained and modified]
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 1, 6, 8-16, 19-21 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (WO 2019/015644 A1; see applicants filed IDS dated 09/16/2022) in view of Karsdal (Br J Clin Pharmacil, 2014, 79:5, 720-732; see applicants filed IDS dated 05/02/2024) and Chaudhari (IJAPBC, 2012, 1(1), 21-34).
For claim 1:
Zhang teaches pharmaceutical composition of the following compound:
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[see compound 8 in page 11; claims 6 and 8].
The above compound reads applicants compound. Please note that if we rotate above molecule by 180o in 3D space, the bold wedge (pointing towards you) becomes dashed wedge (pointing away from you). This is like turning the molecule around and viewing it from the back.
The differences between Zhang and instant claim are as follows:
(i) Zhang is silent on oral pharmaceutical composition.
(ii) Zhang is silent on applicants recited one of the absorption enhancers with recited weight ratios in their compositions.
With regard to (i) and (ii) of above, Karsdal teaches that the primary advantages of oral drug delivery compared with injection or nasal spray administration are greater acceptability and convenience for patient. Karsdal further teaches that the obstacles in oral formulations can be overcame with various strategies to increase bioavailability of proteins and peptides, and suggests introducing ‘absorption enhancers’ in the peptide formulations. [see sections Introduction and Introducing the absorption enhancers 5-CNAC, SNAC, 4-CNAB].
However, the recited absorption enhancers and their advantages in oral formulations of peptides are well known in the art and widely used in the oral formulations of proteins or peptides. For example, Karsdal teaches N-[8-(2-hydroxybenzoyl amino]caprylate or SNAC (aka N-[8-(2-hydroxybenzoyl)amino]octanoic acid) and monosodium N-(4-chlorosalicyloyl)-4-aminobutyrate (4-CNAB), which is also known as 4-[(4- chloro-2-hydroxy-benzoyl)amino]butyric acid, and their advantages in oral peptide formulations [see page 721 and Table 3].
With regard to concentrations or ratios, 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.
Therefore, a skilled person in the art would be motivated to incorporate absorption enhancers in the peptide composition(s) of Zhang and arrive at applicants claimed oral pharmaceutical composition with a reasonable expectation of success.
For claim 6:
Karsdal teaches cited absorption enhancer [see page 721 and Table 3].
For claim 8-16:
Zhang silent on recited excipients and absorption enhancer with specific ratios in their disclosure.
However, known art is very high in pharmaceutical excipients and so, these are well known in the art. For example, Chaudhari teaches various excipients for solid dosage forms and it also teaches specific binders and lubricants, specifically magnesium stearate as a lubricant, povidone as a binder and microcrystalline cellulose as a diluents, polyethylene glycol as plasticizers [see Table 1].
Karsdal teaches cited both absorption enhancers [see page 721 and Table 3].
With regard to concentrations or ratios, 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.
So, combination of art reads applicants claims.
For claim 19-21:
Zhang silent on recited one or more non-active ingredients in their disclosure. However, this can be cured by teachings of Chaudhari, see below:
Chaudhari teaches various excipients for solid dosage forms and it also teaches specific binders and lubricants, specifically magnesium stearate as a lubricant, povidone as a binder and microcrystalline cellulose as a diluents, polyethylene glycol as plasticizers, and further teach buffers to maintain pH, such as citric acid [see Table 1].
With regard to concentrations or ratios, 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.
So, combination of art reads applicants claims.
Based on the above established facts from the cited prior art, it appears that all the claimed elements, i.e, applicants compound A and absorption enhancers 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.
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 composition 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
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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SUDHAKAR KATAKAM
Primary Examiner
Art Unit 1658
/SUDHAKAR KATAKAM/Primary Examiner, Art Unit 1658
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