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 .
The instant application was transferred from Primary Examiner Thomas Heard to the present examiner.
Applicant’s filing of the RCE on 8/3/26 (no amendments and/or arguments following the 5/29/26 Advisory Action and claim scope amendment considerations therein) is acknowledged.
Claims 32 and 39-47 remain pending and examined on the merits.
The examiner welcomes a further interview with applicant’s representative to discuss the claim scope amendment considerations offered in the previous 5/29/26 Advisory Action and again below with the aim to advance prosecution on the merits (see also previous interview summary of record).
Election/Restrictions – Withdrawn
Allowable Subject Matter – Previously Noted;
See Also Further Below Claim Scope Amendment Considerations
Applicants elected SEQ ID NO: 139 as in the species election requirement. SEQ ID NO: 139 has been found free of the prior art. SEQ ID Nos 77, 78, 112, 114, 119, and 120-125 have also been found to be free of the prior art. Were the claims amended thereto, the application would be in condition for allowance, pending traversal of any remaining rejections of record.
Claim Rejections - 35 USC § 112(a) – Written Description,
Modified Commensurate with that in 5/29/26 Advisory Action
Rejection Maintained, No Amendments and/or Arguments
The following is a quotation 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 32 and 39-47, remain 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The courts have stated, for example:
"To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, no that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966." Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include "level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient." MPEP § 2163.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad generic. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618.
The factors considered in the Written Description requirement are:
(1) level of skill and knowledge in the art,
(2) partial structure,
(3) physical and/or chemical properties,
(4) functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and
(5) the method of making the claimed invention.
In the instant case, the claims remain drawn to any stereoisomer or peptidomimetic of the claimed peptides without limit.
(1) Level of skill and knowledge in the art:
The level of skill to practice the art of the instantly claimed invention is high with regard to the various divergent skills necessary to practice the claimed invention which are generally not found in a single individual.
(2) Partial Structure: (3) Physical and/or Chemical Properties: and/or (4) Functional Characteristics:
In the instant case, with regard to claim 32, there remains a lack of guidance as to what stereoisomers or peptidomimetics and with regard to claim 46 as to any amino acid substitution or deletion – even if outside the N-terminal binding sequence without further evidence that substituting or deleting any amino acid outside the N-terminal binding segment will not impact overall structural binding, were in applicant’s possession.
(5) Method of making the claimed invention:
Peptide synthesis commonly known in the peptide arts.
As stated supra, the MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic. It is unquestionable that Claim(s) 32 and 46 are a broad generic, with respect to all possible compounds encompassed by the claims. The possible structural variations are limitless to any class of compound (peptide) where every position is open to unrelated amino acids, or absent.
It must not be forgotten that the MPEP states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence. "MPEP § 2163.
Here, though the claims may recite some functional characteristics, the claims lack written description because there is no disclosure of a correlation between function and structure of the compounds beyond specific compounds disclosed in the examples in the specification that are supposed to support such a large genus.
Peptide
There are twelve (12) example sequences, see Claim 32, and those examples do not demonstrate an essential common core structure that provides the intended function. While having written description for the species of Claim 32, there is insufficient description of a common core sequence in the Markush group, or a common feature among the various species represented in the Markush group that must remain constant, or have a particular physicochemical property (charge, polarity, aromaticity, hydrophobicity, size, etc…), that would allow one of skill in the art to practice the invention as claimed. With so many substitutions being made with unrelated amino acids, and those substitution not being limited to a single point mutation at a time, one does not have any guidance as to which positions might change the intended structure/function of the peptide/protein, or just turn it into molecular weight marker. The Markush appears to be expanded from a small set of species to what might be done to have compounds that might function in the manner intended (agonist, antagonist, etc…), rather than an actual Markush that conveys essential structure function relationship to the intended use. Further, modifying by substitution or deletion of any amino acid may impart different physicochemical properties.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.")
Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Response to RCE Filing – No Amendments and/or Arguments;
See Also Below Claim Scope Amendment Considerations (Per Advisory Action)
No amendments and/or arguments were filed with the 8/3/26 RCE.
As further stated in the Advisory Action mailed 5/29/26 and retained as there were no amendments and/or arguments filed in the 8/3/26 RCE:
Applicant's arguments have been fully considered but not deemed persuasive. The specification description, definitions, and/or test data, and the arguments and/or evidence of record are still not found to support that applicant was in possession of the full breadth of the claim scope at the earliest effective filing date.
Regarding independent claim 32, the specification does not support that applicant was in possession of 'any' stereoisomer and peptidomimetic of peptide SEQ ID NOS: 77-78, 112, 114, 119, 120-125, or 139; the scope still claimed. But see claim scope considerations with relevant passages of specification support applicant may weigh below.
Regarding independent claim 46, the specification does not support that applicant was in possession of substituting OR deleting 'any' amino acid position beyond the asserted N-terminal binding amino acids 1-12 of peptide SEQ ID NOS: 77-78, 112, 114, 119, 120-125, or 139. There is insufficient guidance and/or test data to show any amino acid position therein may be deleted and/or substituted with any other amino acid (conservative or non-conversative) and still confer binding to the respective CLR/RAMP1 2, and/or 3 receptor.
The below claim scope considerations with relevant passages of specification support applicant may weighed for filing by amendment (see e.g. instant PGPUB para's 58, 61, 135, 176, 220, 221); see also peptide binding support further below:
CLAIM SCOPE AMENDMENT CONSIDERATIONS (PER ADVISORY ACTION)
--1-47. (canceled)
48. (New) A CLR/RAMP1, 2, and 3 receptor antagonist polypeptide, comprising:
the amino acid sequence selected from the group consisting of SEQ ID NOS: 77-78, 112, 121, and 125;
polypeptides thereof comprising one or more modifications selected from the group consisting of attaching a hydrophilic polymer at the N-termini; amidating the C-termini; and substituting one or more L-amino acids with their corresponding D-amino acid;
wherein the polypeptide is a CLR/RAMP1, 2, and 3 receptor antagonist.
49. (New) A CLR/RAMP1 receptor antagonist polypeptide, comprising:
the amino acid sequence selected from the group consisting of SEQ ID NOS: 114, 120, 122-124, and 139;
polypeptides thereof comprising one or more modifications selected from the group consisting of attaching a hydrophilic polymer at the N-termini; amidating the C-termini; and substituting one or more L-amino acids with their corresponding D-amino acid;
wherein the polypeptide is a CLR/RAMP1 receptor antagonist.
50. (New) A CLR/RAMP2 receptor antagonist polypeptide, comprising:
the amino acid sequence of SEQ ID NO: 119;
a polypeptide thereof comprising one or more modifications selected from the group consisting of attaching a hydrophilic polymer at the N-termini; amidating the C-termini; and substituting one or more L-amino acids with their corresponding D-amino acid;
wherein the polypeptide is a CLR/RAMP2 receptor antagonist.
51. (New) The CLR/RAMP receptor antagonist polypeptide of any one of claims 48-50, comprising a mini-PEG moiety attached at the N-termini.
52. (New) A pharmaceutical formulation comprising one or more CLR/RAMP receptor antagonist polypeptides of claims 48-50 and a pharmaceutically acceptable excipient.
53. (New) The pharmaceutical formulation of claim 52, wherein the antagonist is provided in a dose of from 1 ng/kg weight to 100 mg/kg weight.
54. (New) The pharmaceutical formulation of claim 52, wherein the antagonist is provided in a dose of from 0.005 mg to 5 mg.
55. (New) The pharmaceutical formulation of claim 52, formulated for administration selected from the route consisting of parenteral, pulmonary, nasal, sublingual, lingual, buccal, dermal, transdermal, conjunctival, and optic.
56. (New) The pharmaceutical formulation of claim 52, comprising a formulation consisting of a single polypeptide species of any one of claims 48-50.
57. (New) The pharmaceutical formulation of claim 52, comprising a formulation comprising more than one polypeptide species of any one of claims 48-50.
58. (New) The pharmaceutical formulation comprising a CLR/RAMP receptor antagonist of claim 52, wherein the pharmaceutically acceptable excipient comprises a pharmaceutically acceptable salt.--
SUPPORT: PEPTIDES & CLR/RAMP RECEPTOR BINDING SUPPORT
CLR/RAMP 1,2, & 3 antagonist peptide sequence
TVQKLAHQIYQFTDKDKDNSAPVDPSSPHSY-NH2 (SEQ ID NO: 77)
KVQKLAHQIYQFTDKDKDNSAPVDPSSPHSY-NH2 (SEQ ID NO: 78)
KVQKLAHQIYQFTDKDSAPVDPSSPHSY-NH2 (SEQ ID NO: 112)
KVQKLAHQIYQFTDKDSAPVDPSSPHSY-NH2 (SEQ ID NO: 121)
KVQKLAHQIYQFTDKSAPVDPSSPHSY-NH2 (SEQ ID NO: 125)
CLR/RAMP1-specific antagonist peptide sequence
KVQKLAHQIYSAPVDPSSPHSY-NH2 (SEQ ID NO: 114)
KVQNLSHRLWQLMGPAGSAPVDPSSPHSY-NH2 (SEQ ID NO: 120)
KVQKLAHQIYSAPVDPSSPHSY-NH2 (SEQ ID NO: 122)
KVQKLAHQISAPVDPSSPHSY-NH2 (SEQ ID NO: 123)
KVQKLAHQSAPVDPSSPHSY-NH2 (SEQ ID NO: 124)
KVQKLSAPVDPSSPHSY-NH2 (SEQ ID NO: 139)
CLR/RAMP2-specific antagonist peptide sequence
KVQKLAHQIYQFTDKDVAPRSKISPQGY-NH2 (SEQ ID NO: 119)
Additionally, the previous response to amendments/arguments is carried forward here as still equally applicable. [See also previous Interview Summary.]
Claim 32, at a minimum, remains rejected for insufficient representative examples as to “superantagonist polypeptides” directed to stereoisomers and peptidomimetics and what the structure thereof is.
Claim 32 and 46 is rejected after amendment as to what falls inside v. outside a ‘superantagonist’, there being insufficient support to establish the BRI relevant to possession thereof. Thus, it was recommended applicant amend those specific CLR/RAMP receptors that were shown to be treatable in order to confer structure + function relevant to any single substitution/deletion outside the critical/essential N-terminal 12mer region of the claimed peptides, such that any such substitution/deletion must still retain function in order to fall within the scope of the claimed and intended invention.
Previously noted and retained for continuity, Applicant had asserted:
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The above does not address the lack of guidance as to the structural possession of claim 32 stereoisomers or peptidomimetics beyond any described but not yet claimed. Further, the above does not remedy that claim 46 remains drawn to unknown peptide substitutions below 100% identity even outside the N-terminal binding sequence which may equally affect structure + function but for which there is a lack of guidance and thus possession as to what positions may be modified and with what amino acids and still retain such. The Chang reference is only very specific about a single point mutation.
Thus, the rejection as to possession is maintained, for at least the reasons of record. The examiner remains open to interview at any time to advance prosecution on the merits.
Conclusion
All claims are identical to [no amendments/arguments filed in 8/3/26 RCE following the 5/29/26 Advisory Action] or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 MAURY AUDET whose telephone number is (571)272-0960. The examiner can normally be reached on M-Th. 7AM-5:30PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached on 571-270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
/MAURY A AUDET/Primary Examiner, Art Unit 1654
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