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 .
This is the First Office Action on the Merits of US 18/036,382 filed on May 10, 2023 which is a 371 of PCT/US2021/059416 filed on 11/15/2021 which claims US priority benefit of US Provisionals 63/211,972 filed on 06/17/2021 and 63/114,976 filed on 11/17/2020.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows: The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/114,976 filed on 11/17/2020, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The ‘976 does not disclose the presently claimed inventions.
Thus, the present claims receive an effective filing date of US Provisional 63/211,972 filed on 06/17/2021.
Election/Restrictions
Applicant's election with traverse of invention Group II (e.g., claims 2-12, drawn to a lipopeptide of formula IV, in the reply filed on January 21, 2026 is acknowledged. The traversal is on the ground(s) that the applicants state that the claims are presently amended to change the dependencies of claims 13 and claim 20 which changes the scope of invention Group III (claims 13-19) and Group IV (claims 20-21) to fall within the scope of formula IV as recited in Group II. The changing of claim dependencies is addressed below as to how it may change which groups the present claims fall into. However, the changing of present claim dependencies does not affect the validity of the restriction requirement mailed on January 21, 2026.
Thus, the applicants’ traverse is not found persuasive because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement. Therefore, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The requirement is still deemed proper and is therefore made FINAL.
In light of the present claim amendments, Group II presently contains claims 2-12, 13-19, 20-21, 24, 42, and 46.
Claims 1, 22-23, 25-37, and 41 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention Groups, there being no allowable generic or linking claim.
Based on the applicants’ species election, claims 3-6 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. However, in view of the prior art of Robert et al (herein), claim 3 is REJOINED.
Applicant’s following election of species in the reply filed on January 21, 2026 is acknowledged.
Applicant did not elect species (A) stating they did not elect Group I.
(B): Regarding the compound listed in claim 2:
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Applicant elects the following compound as the one structure listed in claim 2 with designation of R1, R2, R2a, R2x, and R2y (compound 25 of Table A):
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Further, applicant specifies:
R1 = at least one optionally substituted amino acid moiety (See instant claims 3-6);
R2 =
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;
R2a = oxo (See instant claim 11 and elected compound);
R2x and R2y are taken together with the atoms to which they are attached to form an optionally substituted 5-membered heterocycle. (See instant elected compound above & claims 9-10.) Applicant states that this species election reads on claims 2-12, 13-15, 17-19, 20-21, 24, 42, and 46. Thus claim 16 is withdrawn to non-elected species (B).
C) Applicant elects Phe-Thr-Val, wherein each Phe and Val is N-methylated as the one structure listed in claim 6 by designation of one of the species listed for R1.
D) Applicant elects R2b is H (see instant claim 10 & elected compound). Applicant states that the claims 2-15, 17-21, 24-37, 41-42, and 46 read on the elected species.
E) Applicant elects “oxo” as the R2a listed in claim 11.
F) Regarding the election of the one structure listed in claim 13 with designation of one single species of each of the variable elements of IV-A:
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Applicant elects the same structure as elected for claim 2 (compound 25 of Table A):
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Further, Applicant specifies:
Z =
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;
R2a = oxo (See instant claim 11 and elected compound);
R2x and R2y are taken together with the atoms to which they are attached to form an optionally substituted 5-membered heterocycle. (See instant elected compound above & claims 9-10.)
R3 = alkenyl;
R4 = alkyl (see limitation of claim 6 for N-methylated Phe and Val);
Each R5 and R8 is independently a hydrophobic side chain of Val and Phe, wherein the hydrophobic side chain is optionally substituted; (note that the elected compound elects Phe-Thr-Val as the R1 group);
R6 = alkyl & R7 = OH (side chain of Thr).
G) Applicant elects the following 8th listed compound as the one species of the nine compounds listed in claim 20. However, this compound does not correspond to the elected species of claim 2 from which claim 20 depends; thus, claim 20 is withdrawn to nonelected species (B).
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H) Applicant elects the following as the one species of the compound listed in claim 21 which is the 7th listed compound. However, this compound does not correspond to the elected species of claim 20 from which claim 21 depends; thus, claim 21 is withdrawn to nonelected species (G).
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(I & J) Applicant did not elect species I or J stating they did not elect Group II.
(K) Applicant elects asthma.
Claim status
Claims 38-40, 43-45, and 47 are cancelled.
Claims 1-37, 41-42, and 46 are pending.
Claims 1, 22-23, 25-37, and 41 are withdrawn to non-elected invention group.
Claims 4-6, and 20-21 are withdrawn to non-elected species.
Claims 2-3, 7-12, 13-19, 24, 42, and 46 are under examination.
Information Disclosure Statement
The IDS statements filed on 01/22/2026, 05/28/2024, 05/18/2023 have been considered by the examiner. References not in the English language have only been considered to their English language abstracts.
Claim Objections
Claims 6 and 46 are objected to because of the following informalities:
Claim 6 recites “claim Claim 2” in line 1 which should be corrected.
Claim 46 recites “such composition” in line 4. Since the term “composition” appears twice in line 2, for improved clarity amend line 2 as follows: …a dosage form of a composition comprising .
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.
Claims 2-3, 7-12, 13-19, 24, 42, and 46 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for the compound #25 shown on page 20 of the specification for use in a method for treating an eosinophilic inflammatory condition in a human in need thereof, does not reasonably provide enablement for use of the breadth of the lipopeptides encompassed by the claims for treating such condition. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Many factors are to be considered when determining if sufficient evidence exists to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue". These factors include 1) the breadth of the claims, 2) the nature of the invention, 3) the state of the prior art, 4) the level of one of ordinary skill, 5) the level of predictability in the art, 6) the amount of direction provided by the inventor, 7) the existence of working examples, and 8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
The nature of the invention: The nature of the invention encompasses pharmaceutical lipopeptide compounds for treating medical conditions in a human subject. The invention is in a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001). The claims are drawn to pharmaceuticals and dosage forms of the lipopeptides in claim 2
The breadth of the claims: The claims are drawn to any species of lipopeptides recited in base claim 2 for treatment of an eosinophilic inflammatory condition in a human. The compounds include isomers of the structures. The specification informs that isomers have the same molecular formula but differ in the nature of sequence of bonding of their atoms. (See page 25). The specification states in page 33 that the term “treating” encompasses “ameliorating the disease state and/or providing a remission (whether partial or total) of the condition, disease or disorder and/or decreasing the dose of one or more other medications required to treat the condition, disease or disorder”. The claims are drawn to pharmaceuticals and dosage forms of the lipopeptides in claim 2. However, the claims are broad to any subject. In page 35, the specification states that the human subject may be a child including a child less than 1 year old. In para 0108, the specification state that “exemplary dosage levels of microcolins for a human may be between 00.01 mg/kg to 100mg/kg weight of the human”.
The state of the prior art: The state of the prior art is shown in US Patent 4,665,053 to Robert et al. Robert et al discloses a lipopeptide of formula (IV). Robert et al disclose there is unpredictability in the properties of such lipopeptides depending on the precise structures. (See entire document; col 6, lines 60-65: Methyl ester of Oleoyl-L-Alanyl-L-Alanyl-L-Proline).
The predictability in the art: It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F. 2d 833,166 USPQ18 (CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. In the instant case, the instantly claimed invention is highly unpredictable as to whether a given species of lipopeptide would be useful for treating a respiratory disease. In the absence of a showing of a nexus between the breadth of inflammatory diseases and the effectiveness by the claimed lipopeptides, one of ordinary skill in the art is unable to fully predict possible results from the administration of the compound of claim 2 and thus fail to provide sufficient scope of enablement for the use of such compounds including dosages for such compounds. Those of skill in the art recognize that in vitro assays and or cell-cultured based assays are generally useful to observe basic physiological and cellular phenomenon such as screening the effects of potential drugs. However, clinical correlations are generally lacking. The greatly increased complexity of the in vivo environment as compared to the very narrowly defined and controlled conditions of an in-vitro assay does not permit a single extrapolation of in vitro assay to human diagnostic efficacy with any reasonable degree of predictability. In vitro assays cannot easily assess cell-cell interactions that may be important in a particular pathological state. Furthermore, it is well known in the art that cultured cells, over a period time, lose phenotypic characteristics associated with their normal counterpart cell type. Freshney (Culture of Animal Cells, A Manual of Basic Technique And Specialized Applications, John Wiley & Sons, Inc., 2010, Hoboken, New Jersey, Chapter 1, pages 1-10) teach that it is recognized in the art that there are many differences between cultured cells and their counterparts in vivo. These differences stem from the dissociation of cells from a three-dimensional geometry and their propagation on a two-dimensional substrate. Specific cell interactions characteristic of histology of the tissue are lost. The culture environment lacks the input of the nervous and endocrine systems involved in homeostatic regulation in vivo. Without this control, cellular metabolism may be more constant in vitro but may not be truly representative of the tissue from which the cells were derived. This has often led to tissue culture being regarded in a rather skeptical light (p. 8, see Section: Major Differences In Vitro).
The amount of direction or guidance provided in the specification and the presence or absence of working examples: The specification shows methods of making some of the lipopeptides of the present claims. Example 1 shows the synthesis of Compound 1b. Example 2 shows the synthesis of Compound 5a. Example 3 shows the synthesis of Compound 6a. Example 4 shows the synthesis of Compound 7a. Example 5 shows the synthesis of Compound 8a. Example 6 shows the synthesis of Compound 9a. Example 7 shows the synthesis of Compound 10a. Example 8 shows the synthesis of Compound 11a. Example 9 shows the synthesis of Compound 12a. Example 10 shows the synthesis of Compound 13a. Example 11 shows the synthesis of Compound 14a. Example 12 shows the synthesis of Compound 15a. Example 13 shows the synthesis of Compound 16a. Example 14 shows the synthesis of Compound 17a. Example 15 shows the synthesis of Compound 18a. Example 16 shows the synthesis of Compound 19a. Example 17 shows the synthesis of Compound 20a. Example 18 shows a biological example regarding the percent eosinophil apoptosis in Allergic Human purified peripheral blood Eosinophils using tissue culture. Twenty-six compounds shown in Table 1 were tested compared to an ApoA-IV control. Elected species compound #25 was not included but related compound #25a was included. Example 19 shows CD11b change (100% as baseline) on PMNL surface stimulated by 2.5 nmCCL11. Eleven compounds shown in Table 2 were tested. Elected species compound #25 was not included.
The quantity of experimentation needed: The quantity of experimentation needed is undue. One skilled in the art would need to determine what respiratory conditions would be benefited by the treatment with the broadly claimed lipopeptides of present claim 2.
The level of the skill in the art: The level of skill in the art is high. However, due to the unpredictability in the pharmaceutical art, it is noted that each embodiment of the invention is required to be individually assessed for physiological activity by in vitro and in vivo screening to determine which compounds exhibit the desired pharmacological activity and which conditions would benefit from this activity.
Thus, the specification fails to provide sufficient support of the broad use of the lipopeptides of claim 2 for the treatment of a respiratory disease or eosinophilic inflammatory condition in a human subject.
Genentech Inc. v. Novo Nordisk A/S (CA FC) 42 USPQ2d 1001, states that "a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion" and "[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable".
Therefore, in view of the Wands factors and In re Fisher (CCPA 1970) discussed above, to practice the claimed invention herein, one of ordinary skill in the art would have to engage in undue experimentation to test which diseases can be treated by the compounds of the instant claims, with no assurance of success.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 2-3, 24, 42, and 46 are rejected under 35 U.S.C. 102(a)(1) or (a)(2) as being anticipated by US Patent 4,665,053 to Robert et al, issued May 12, 1987 (IDS ref).
Regarding claims 2-3, Robert et al discloses a lipopeptide of formula (IV). (See col 6, lines 60-65: Methyl ester of Oleoyl-L-Alanyl-L-Alanyl-L-Proline). Regarding claim 2, Robert discloses that: R1 is at least one optionally substituted amino acid moiety. Regarding claim 3, Roberts et al discloses the lipopeptide having three amino acid moieties. Further, Roberts et al discloses that R2 is the third structure listed, wherein R2x and R2y are taken together with the atoms to which they are attached to form an optionally substituted 5-membered heterocycle and further discloses that R3 is alkenyl (See col 6, lines 60-65: Methyl ester of Oleoyl-L-Alanyl-L-Alanyl-L-Proline).
Thus, Robert et al meets the limitations of claims 2-3 being drawn to a lipopeptide of formula (IV):
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(or a salt thereof, including any isomers of the foregoing), wherein: R¹ is three optionally substituted amino acid moieties;
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R²ᵃ is H, OXO or optionally substituted alkyl;
R²ₓ is alkyl, optionally substituted with -OH or -COOH;
R²y is H or alkyl; or
R²ₓ and R²y are taken together with the atoms to which they are attached to form an optionally substituted 5-membered heterocycle; and
R³ is alkenyl.
Regarding claim 24, Robert et al disclose a pharmaceutical composition comprising a lipopeptide of claim 2, and a pharmaceutically acceptable excipient. See column 5, lines 19-67; reference claim 11.
Regarding claim 42, Robert et al disclose a container comprising a composition comprising a lipopeptide of claim 2. See column 5, lines 19-67. Note that the limitation of a label containing instructions for use of such composition is not generally afforded patentable weight for purpose of applying prior art.
Regarding claim 46, Robert et al disclose a kit (composition) comprising a dosage form of a composition comprising a lipopeptide of claim 2. See column 5, lines 19-67; reference claims 11-12. Note that the limitation of a package insert containing instructions for use of such composition is not generally afforded patentable weight for purpose of applying prior art.
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 2, 12, 13, 16-19, 24, 42, and 46 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 19/584,637 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the co-pending claims anticipate or are essentially identical to the instant claims.
Regarding instant claims 2 and 13, copending claim 1 recites the same compound shown in instant claim 13.
Regarding instant claim 12, copending claim 4 recites compounds wherein R3 is C2-C30 alkenyl.
Regarding instant claim 16, copending claim 1 recites compounds wherein R2x and R2y are taken together with the atoms to which they are attached to form 5-membered heterocycle substituted with -OH.
Regarding instant claim 17, copending claim 4 recites compounds wherein R3 is C2-C30 alkenyl.
Regarding instant claim 18, copending claim 4 recites compounds wherein R5 is the hydrophobic side chain of Leu or Phe.
Regarding instant claim 19, copending claim 1 recites compounds wherein R7 is OH.
Regarding instant claims 24, 42, and 46, copending claims 5, and 12-17 recite a pharmaceutical composition and a pharmaceutically acceptable excipient, container, a dosage form, a container and a kit and a dosage form and a pharmaceutical composition and a pharmaceutically acceptable excipient and each require the compound of copending claim 1.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Free of the prior art
The elected species of compound #25 appears free of the prior art.
Conclusion
No claim is allowed.
Related prior art which may be applied in a future office action if appropriate:
Yu et al in “Cytotoxic Microcolin Lipopeptides from the Marine Cyanobacterium Moorea producens (Journal of Natural Products, 2019, Vol 82, pages 2608-2619, published August 30, 2019).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CATHERINE S HIBBERT whose telephone number is (571)270-3053. The examiner can normally be reached M-F 8:00-5:00.
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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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CATHERINE S. HIBBERT
Primary Examiner
Art Unit 1658
/CATHERINE S HIBBERT/Primary Examiner, Art Unit 1658
Prosecution Insights