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 3, 4, 9, 13, 14, 16, 17, 22, 23, 25-27, 29-36, 38-40, 42-45, and 47-65 have been cancelled in a previous communication.
Claims 1, 2, 5-8, 10-12, 15, 18-21, 24, 28, and 37 are pending and under current examination.
The claims are examined in view of the species election SEQ ID NO: 10.
All rejections not reiterated have been withdrawn.
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.
The factual inquiries 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, 2, 5-8, 10-12, 15, 18-21, 24, 28, and 37 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (US2007/0196416; publication date: 08/23/2007) in view of Hay et al. (J Pharmacol Exp Ther Vol 369, 9-25; publication: 04/2019).
The claims are examined in view of the elected species: SEQ ID NO 10.
With regard to claims 1, 2, and 28, Li discloses a stabilized biodegradable polymeric composition useful as a controlled release delivery system for peptide agents comprising a salt of a peptide agent and a polymer in an organic solution, with optional excipients (abstract). Preferably the composition is injectable (0019), the polymer and the peptide may be dissolved in the pharmaceutically acceptable solvent (0020), and the composition may be formulated as a gel (0029). The peptide may be an angiotensin (0036). The polymer is preferably poly(lactic-co-glycolic acid) having lactic acid to glycolic acid ratio of from 50:50 to 100:0 (PLGA, i.e. the polymer has a mixture of poly(lactic acid) monomers and poly(glycolic acid) monomers at the stated ratios). In the case of a LA:GA ratio of 100:0, the polymer is PLA and 100% of monomers are poly(lactic acid) (0052).
Li does not disclose the elected species SEQID 10, i.e. a D-amino acid heptapeptide having the first six amino acids of Ang(1-7) and a terminal glycosylated serine residue (see table 2, page 20 of the instant specification, ANG-(1-7)_V5 (PNA5) corresponds to SEQID No 10). Additionally, Li exemplifies peptides other than angiotensins.
Hay discloses an angiotensin-(1-7) glycosylated Mas receptor agonist, PNA5 (Ang (1-6)-Ser-Glc-NH2, (title, abstract, page 10, left col; i.e. the elected species of oligopeptide SEQID10). PNA5 penetrates the blood-brain barrier more effectively than the naturally occurring ang-(1-7) and has greater stability (page 10, left col). Hay envisions sustained treatment with PNA5 in order to attenuate or reverse vascular contribution to cognitive impairment and dementia due to inflammatory disease (abstract, page 10, left col).
It would have been prima facie obvious to formulate PNA5 according to Li’s invention. The artisan of ordinary skill would have been motivated to do so in order to provide a stable, sustained release preparation of the peptide drug. The skilled artisan would have had a reasonable expectation of success because Li lays out detailed instructions to formulate peptide drugs, and PNA5 has several basic amino acids containing amine groups (Hay Fig 1(A)), and therefore meets the requirement for Li’s invention (see Li 0019, which indicates the peptide must have a basic amine group that can be neutralized with a strong acid).
With regard to the pharmacokinetic profile required by instant claims 1 and 2, Li describes including burst effect reducing materials (0015), release rate modifying agents (0016), and that the peptide agent is released into the surrounding tissue fluids and to the pertinent body tissue or organ as the polymer degrades (0021). Li describes polymer molecular weight as a factor that may be determined by a person of ordinary skill in the art, as well as selecting molecular weight of the polymer based on desired polymer degradation rate, mechanical strength and rate of dissolution of polymer in organic solvents (0050). In para 0054, Li states: “The type, molecular weight, and amount of biodegradable polymer present in the compositions can influence the length of time in which the peptide agent is released from the controlled release implant. The selection of the type, molecular weight, and amount of biodegradable polymer present in the compositions to achieve desired properties of the controlled release implant can be determined by simple experimentations.” Li provides further guidance on how solvent selection can affect pharmacokinetic profile in terms of burst and diffusion (0061). The examiner does not consider the pharmacokinetic limitations recited in instant claims 1 and 2 to patentably define over the cited prior art because Hay provides motivation for sustained delivery of PNA5 (page 10, left col: “sustained treatment with PNA5 [may] attenuate or reverse the VCID/HF-induced cognitive impairment”) and Li provides detailed instruction on the variables that may be optimized to reduce burst and provide stable extended release of peptide drugs, including angiotensins. It would have been prima facie obvious to optimize the release profile of PNA5 according to Li’s instruction to achieve a desired pharmacokinetic profile.
With regard to claims 5-7, as noted above, the PLGA/PLA polymer disclosed by Li may have a range in lactic acid : glycolic acid of from 50:50 to 100:0 (0052) and suitable molecular weights range from 2,000 to 100,000 Da (0050). These ranges overlap with the ranges in percent lactic and glycolic acid as well as the range in molecular weight required by the instant claims. See MPEP 2144.05(I): In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).
With regard to claim 8, the polymer may be carboxylic acid capped or ester capped (0052).
With regard to claims 10, 11, and 18-20, Li discloses ranges in amount of peptide active agent, polymer, and solvent of 0.01 – 40% of a beneficial salt of a peptide agent (0073) 10-70% polymer (0073), and 30-80% of the organic solvent (0061). These ranges along with the additional formulation guidance noted above and the dose of 1mg/kg PNA5 disclosed by Hay (page 12, right col), provide starting points for optimization of dose, and quantity of excipients to achieve a desired pharmacokinetic profile. For this reason, the examiner does not consider the limitations of instant claims 10, 11, and 18-20 regarding percentages of polymer, active peptide, and solvent, dose of active peptide, or weight ratio of polymer to oligopeptide to patentably define over the cited prior art. These are each parameters that one of ordinary skill would have optimized in order to achieve effective sustained treatment with PNA5 to achieve effective concentrations of the oligopeptide at the target site. See MPEP 2144.05(II)(A): Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
With regard to claim 12, the organic solvents may be selected from inter alia DMSO, NMP, and benzyl benzoate (0060).
With regard to claim 15, as noted above, the composition may contain a release rate modifier (0016).
With regard to claim 21, Li’s formulation may be pre-filled in a single syringe in a ready-to-use configuration (0007).
With regard to claim 24, Li’s invention solves the problem of storage stability of peptide agents in polymer/solvent solutions. The examiner considers it a matter of routine optimization to achieve Li’s stated objective of improving the stability of the particular peptide by following the guidance contained in Li.
With regard to claim 37, as noted above, the peptide is an acid addition salt form of the oligopeptide (abstract).
Response to Arguments
Applicant's arguments filed 11/07/2025 have been fully considered but they are not persuasive.
On pages 5-6, Applicant argues that Li describes prior art methods as not entirely satisfactory for a large number of peptide agents that may be effectively delivered by the approaches known in the prior art at the time of Li’s invention. Applicant argues further on page 6 that Li only discloses one example, which contains leuprolide, and that leuprolide has a sequenced different from angiotensin. Applicant concludes that one having ordinary skill would have lacked reasonable expectation of success formulating PNA5, e.g., in Li’s composition.
Applicant’s arguments are not persuasive because the cited section of Li is from the background and is the problem that Li’s invention solves. In the description of their invention, Li states: “The peptide agent of the present invention contains at least one basic group. The peptide agent may be any peptide, oligopeptide, polypeptide, or protein that is capable of providing a biological, physiological or therapeutic effect in an animal or human. The peptide agent may be any one or more of known biologically active peptide, oligopeptide, polypeptide, or protein recognized in any documents cited herein or otherwise recognized in the art. The peptide agent may also stimulate or inhibit a desired biological or physiological activity within the animal or human, including without limitation, stimulate an immunogenic or immunological response.” (0010)
Thus, Li discloses that the peptide can be any peptide having a basic amino acid and specifically states that angiotensins can be formulated (0036). See MPEP 2121: When the reference relied on expressly anticipates or makes obvious all of the elements of the claimed invention, the reference is presumed to be operable. Once such a reference is found, the burden is on applicant to rebut the presumption of operability. In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980).
Conclusion
No claims are allowed.
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 KATHERINE PEEBLES whose telephone number is (571)272-6247. The examiner can normally be reached Monday through Friday: 9 am to 3 pm.
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/KATHERINE PEEBLES/ Primary Examiner, Art Unit 1617