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
The claims of 29 November 2024 are entered.
Claims 10-13 have been canceled. Claims 1-9, 14, and 15 are pending and are being examined on the merits.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
Specification
The disclosure is objected to because of the following informalities: At least Tables 3-1 through 3-4 and 9-2 are of low resolution such that the elements and compounds discussed within are not able to be ascertained with any degree of confidence.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-9, 14, and 15 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are broadly written and recite various properties required of the peptides. This brings rise to questions of possession of the genus as claimed. While the lauroyl-L-carnitine is limited, the associated peptides are very broadly claimed based primarily on their properties.
Firstly, the claims recite a peptide having a ClogP of 4-25. Secondly, the claims recite a peptide having a solubility of 10 mg/mL or less in 50 mM phosphate buffer at pH 6.5 and at 37°C and 1 atmosphere. These recited properties are such that there is no reasonable correlation between the genus and a specific peptide structure. The claims are being defined by a property rather than by any particular structure that leads the skilled artisan to an understanding of the breadth associated with the peptide portion.
The specification discloses 12 compounds and cyclosporine A in Tables 3-1 to 3-4. These are all cyclic peptides and appear to be KRAS inhibitors. Each appear to satisfy the ClogP requirements per [0158]. Compounds 1-12 also appear to satisfy the solubility requirements per [0170]. It would appear each of these is combined with lauroyl-L-carnitine, but this is not readily verifiable since the text in Tables 9-1 to 9-6 are all of low resolution rendering the text largely indecipherable.
At best, one of ordinary skill in the art would recognize possession of the twelve compounds as found in the specification, along with cyclosporine A. These peptides are limited in scope and do not represent the full genus of peptides defined by the property of either a ClogP of 4-5 or a solubility of 10 mg/mL or less in 50 mM phosphate buffer at 37°C and 1 atm. There is no reasonable extension from these peptides to any other structures that represent the claimed peptides, especially given that no particular structure is imposed by the claim language.
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014).
Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the inventor was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date." See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014).
In this case, the species as disclosed do not serve as a representative number of species given that the claim defines the peptides by their properties rather than by a specific structure. There is no reasonable correlation between any given peptide and the claimed properties to give one of ordinary skill in the art an understanding of the genus. Accordingly, one of ordinary skill in the art has no means to ascertain if the twelve species as disclosed are truly representative of the genus as claimed. Since the species do not fully represent the genus as claimed, possession of the genus would not be recognized. As such, written description is lacking.
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, 7-9, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Lamers C (Future Drug Discovery 4:2, published 11 July 2022, hereafter referred toa s Lamers).
Lamers discusses issues with peptide-based therapeutics (see e.g. Abstract). Lamers highlights unfavorable pharmacokinetics, including issues with absorption, distribution, metabolism, and excretion (see e.g. p.4). Cyclosporine A is highlighted as being extensively studied cyclic peptide (see e.g. p.8). Cyclosporine A reasonably contains N-substituted amino acids, as the backbone contains nitrogen atoms modified by a methyl group instead of being a standard NH2. Lamers suggests that delivery technologies utilizing lauroyl-L-carnitine serve to increase delivery through promotion of passive paracellular transport through tight junction loosening, as well as surfactant effects that enhance solubility and allow for traversal across the mucus layer (see e.g. p.10).
The difference between Lamers and the claimed invention is that Lamers does not directly suggest combination of cyclosporine A with lauroyl-L-carnitine.
It would have been obvious to one of ordinary skill in the art to utilize the techniques of Lamers to increase peptide delivery, including by combining cyclized peptides such as cyclosporine A with delivery forms such as those utilizing lauroyl-L-carnitine as a permeation enhancer and a surfactant. The rationale comes from Lamers discussing the dosage form utilizing lauroyl-L-carnitine as a desirable option given the dual action of the modifier in increasing permeability of tight junctions as well as solubilizing the peptide drug. There would have been a reasonable expectation of success because Lamers discloses a limited number of peptide drugs and limited options for increasing peptide delivery and indicates that both the cyclosporine A and lauroyl-L-carnitine were known elements. As further evidence, Ganesh et al. (Medicine in Drug Delivery 9:100079, published 2021) indicates that lauroyl-L-carnitine was utilized as a known permeation enhancer for a variety of oral peptides including leuprolide and octreotide (see e.g. Section 4.7.3) The invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
With respect to claim 2, as noted above Lamers indicates that lauroyl-L-carnitine was considered to increase peptide solubility as a surfactant.
With respect to claim 7, the nitrogen atoms of cyclosporine A are modified by a methyl group.
With respect to claim 8, cyclosporine A is a cyclic peptide compound.
With respect to claim 9, the molecular weight of cyclosporine A is 1,202.635 g/mol.
With respect to claim 15, Lamers indicates cyclosporine A is an immunosuppressant, i.e. it would reasonably be considered a pharmaceutical composition.
Double Patenting
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 conflicting claims 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) 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 www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-9, 14, and 15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 15-25 and 29 of copending Application No. 18/851,191 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘191 application claims an overlapping composition.
The ’191 application claims a combination of a peptide compound and a surfactant, the peptide having (i) one or more N-substituted amino acid residues, (ii) having a ClogP of 4 or more and 25 or less, or (iii) a peptide having a solubility of 10 mg/mL or less at 37°C at 1 atm and in 50 mM phosphate buffer at pH 6.5 (see e.g. claim 15). This is further modified such that the surfactant is lauroyl-L-carnitine (see e.g. claim 29). This overlaps with claim 1.
With respect to claim 2, ‘191 further claims a solubility improver (see e.g. claim 18).
With respect to claim 3, ‘191 claims the same levels of the solubility improver (see e.g. claim 19).
With respect to claims 4 and 5, ‘191 claims a polyoxyethylene structure, including a polyoxyethylene caster oil (see e.g. claims 20 and 21).
With respect to claim 6, ‘191 claims the same levels of the surfactant (see e.g. claim 22).
With respect to claim 7, ‘191 claims the same N-substituted amino acid modification (see e.g. claim 23).
With respect to claim 8, ‘191 claims a cyclic peptide (see e.g. claim 24).
With respect to claim 9, ‘191 claims a molecular weight of 5,000 g/mol or less (see e.g. claim 25).
With respect to claim 14, while ‘191 does not explicitly claim a Caco-2 Papp value, this can reasonably be considered an inherent property of the composition when the peptide compound is combined with the lauroyl-L-carnitine.
With respect to claim 15, ‘191 claims oral administration to a mammal, which implies a pharmaceutical composition (see e.g. claim 15).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZACHARY J MIKNIS whose telephone number is (571)272-7008. The examiner can normally be reached Mon-Thurs 7-5.
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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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/ZACHARY J MIKNIS/Patent Examiner, Art Unit 1658
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