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 .
Election/Restrictions
Applicant's election with traverse of Group I and SEQ ID NO:10 in the reply filed on May 26th, 2026 is acknowledged. The grounds for the traversal are not exchanged. Therefore, the traversal is not found persuasive.
The requirement is still deemed proper and is therefore made FINAL.
The elected species is not found in the prior art, so the search has been expanded to include all the species of Group I and the species election requirement is withdrawn.
Claims 20 and 22-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on May 26th, 2026.
Priority
The instant application claims priority to EP21164384.6, filed March 23rd, 2022, EP21213431.6, filed December 9th, 2021, and 371 National Stage Application PCT/EP2022/057533, filed March 22nd, 2022, under 35 U.S.C. 119(a)-(d). The priority date of March 23rd, 2022 is acknowledged.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
Foreign patent WO2010105184A2 in the IDS filed November 7th, 2023 is not considered as it is later striked out and replaced with WO2010108154A2 in the IDS filed April 3rd, 2024.
The information disclosure statement filed on November 7th, 2023, April 23rd, 2024, April 29th, 2025, December 17th, 2025, and May 22nd, 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claims Status
The claims listing filed on May 26th, 2026 is pending. Claims 20-26 are withdrawn from further consideration for the reasons set forth in the restriction requirement, 37 CFR 1.142(b). Claims 1-9, 16-19, and 21 are being examined on the merits in this office action.
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 1-7 and 21 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. While the applicant does have support for the sequences reduced to practice (SEQ ID NOs: 1, 23, 28-34, 35-46, 3, 49-55, 4-5, 58, 64-78, 6, 67, 80-103 and 21), they do not have support for the complete genus of variants of SEQ ID NO: 1, the core structure shared between claims 1-7 and 21. Please see detailed analysis below.
Claim 1 recites “An ion channel blocker which has Kv1.3 inhibitor activity, or a pharmaceutically acceptable salt thereof, comprising a variant of the sequence QMDMRCSASVECKQKCLKAIGSIFGKCMNKKCKCYPR (SEQ ID NO: 1),wherein the variant differs from SEQ ID NO: 1 by up to ten substitutions, insertions or deletions in total, wherein at least one amino acid in position 7, 8, 9, 10 or 11 of SEQ ID NO: 1 is substituted with an amino acid having a positively charged side chain and/or an amino acid having an aromatic side chain…” However, the specification does not support that the inventors possess the complete recited genus and that the complete genus is able to inhibit Kv1.3.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus. [MPEP 2163 ii)].
The inventors provide direction by testing the Kv1.3 blocker activity in a FLIPR thallium assay of SEQ ID NOs: 10-21 and 1 [Example 2 pg 35-37]; the selectivity of Kv1.3 over Kv1.1, Kv1.2, and Kv1.6, in a patch clamp assay of SEQ ID NO: 10, 12, 1, 22-39, 42-45, 48-49, 4, 52-53, 5, 54-55, 58-60, 62-64, 6, 71-72, 77-79, 81, 89-91, 21, 94, 96-100, and 103; the inhibitory activity of SEQ ID NO: 27-28, 31, 43, 23, 1, 49, 34, and 54 on human peripheral blood mononuclear cells; and the inhibitory activity of inhibitors comprising SEQ ID NOs: 1, 23, 28-34, 35-46, 3, 49-55, 4-5, 58, 64-78, 6, 67, 80-103 and 21. However, sequences reduced to practice by the applicant are not representative of the entire genus of variants of SEQ ID NO: 1 claimed. Nor, would one of ordinary skill in the art be able to attest to the complete genus’s ability to act as a Kv1.3 ion channel inhibitor; the variant may have alterations in the sequence that strip it of its ability to inhibit Kv1.3. Furthermore, the applicant does not disclose relevant, functional characteristics or motifs necessary, or unnecessary for the inhibition of Kv1.3. Thus, while the applicant has support for the specific sequences reduced to practice, they do not have support for the complete genus of variants of SEQ ID NO: 1, wherein the variant differs from SEQ ID NO: 1 by up to ten substitutions, insertions or deletions and at least one amino acid in position 7, 8, 9, 10 or 11 of SEQ ID NO: 1 is substituted with an amino acid having a positively charged side chain and/or an amino acid having an aromatic side chain.
Regarding claim 2, the sequences reduced to practice by the applicant are not representative of the entire genus of variants of SEQ ID NO: 1, wherein the variant differs from SEQ ID NO: 1 by up to ten substitutions, insertions or deletions and at least one amino acid in position 7, 8, 9, 10 or 11 of SEQ ID NO: 1 is substituted with an amino acid having a positively charged side chain and/or an amino acid having an aromatic side chain wherein any substitutions or deletions in the variant of SEQ ID NO: 1 are at amino acid positions selected from positions 1-5, 7-11, 13-15, 17-23, 25, 28-31, 33 and 35-37 of SEQ ID NO: 1. Nor, would one of ordinary skill in the art be able to attest to the complete genus’s ability to act as a Kv1.3 ion channel inhibitor; the variant may have substitutions or deletions in the sequence that strip it of its ability to inhibit Kv1.3. Thus, while the applicant has support for the sequences reduced to practice, they do not have support for the complete genus of variants claimed.
Regarding claim 3, the sequences reduced to practice by the applicant all have a potency IC50 of 50 nM or less on Chinese Hamster Ovary cell lines [pgs 38-40 tables 6-7]. and on human peripheral blood mononuclear cells [pgs 41-42 tables 8 a-b]. However, theses sequences are not representative of the entire genus of variants of SEQ ID NO: 1, wherein the variant differs from SEQ ID NO: 1 by up to ten substitutions, insertions or deletions and at least one amino acid in position 7, 8, 9, 10 or 11 of SEQ ID NO: 1 is substituted with an amino acid having a positively charged side chain and/or an amino acid having an aromatic side chain. Nor, would one of ordinary skill in the art be able to attest to the complete genus’s ability to act as a Kv1.3 ion channel inhibitor; the variant may have alterations in the sequence that strip it of its ability to inhibit Kv1.3 with an IC50 of 50 nM or less. Thus, while the applicant has support for the sequences reduced to practice, they do not have support for the complete genus of variants claimed.
Regarding claim 4, the sequences reduced to practice by the applicant are not representative of the entire genus of variants of SEQ ID NO: 1, wherein the variant differs from SEQ ID NO: 1 by up to ten substitutions, insertions or deletions and at least one amino acid in position 7, 8, 9, 10 or 11 of SEQ ID NO: 1 is substituted with an amino acid having a positively charged side chain and/or an amino acid having an aromatic side chain, wherein the amino acid having a positively charged side chain is selected from the group consisting of H, K, hK, R, Orn, 2,3-diaminopropanoyl, 2,4-diaminobutanoyl, 2-amino-3- guanidinopropionyl, and 4-amino-phenylalanine (F(4-NH2)); and/or the amino acid having an aromatic side chain is selected from the group consisting of F, W and Y. Nor, would one of ordinary skill in the art be able to attest to the complete genus’s ability to act as a Kv1.3 ion channel inhibitor; the variant may have alterations in the sequence that strip it of its ability to inhibit Kv1.3. Thus, while the applicant has support for the sequences reduced to practice, they do not have support for the complete genus of variants claimed.
Regarding claim 5, the sequences reduced to practice by the applicant are not representative of the entire genus of variants of SEQ ID NO: 1 claimed. Nor, would one of ordinary skill in the art be able to attest to the complete genus’s ability to act as a Kv1.3 ion channel inhibitor; the variant may have alterations in the sequence that strip it of its ability to inhibit Kv1.3. Furthermore, the applicant does not disclose relevant, functional characteristics or motifs necessary, or unnecessary for the inhibition of Kv1.3. Thus, while the applicant has support for the specific sequences reduced to practice, they do not have support for the complete genus of variants claimed.
Regarding claim 6, the sequences reduced to practice by the applicant are not representative of the entire genus of variants of SEQ ID NO: 1 claimed. Nor, would one of ordinary skill in the art be able to attest to the complete genus’s ability to act as a Kv1.3 ion channel inhibitor; the variant may have alterations in the sequence that strip it of its ability to inhibit Kv1.3. Furthermore, the applicant does not disclose relevant, functional characteristics or motifs necessary, or unnecessary for the inhibition of Kv1.3. Thus, while the applicant has support for the specific sequences reduced to practice, they do not have support for the complete genus of variants claimed.
Regarding claim 7, the sequences reduced to practice by the applicant are not representative of the entire genus of variants of SEQ ID NO: 1 claimed. Nor, would one of ordinary skill in the art be able to attest to the complete genus’s ability to act as a Kv1.3 ion channel inhibitor; the variant may have alterations in the sequence that strip it of its ability to inhibit Kv1.3. Furthermore, the applicant does not disclose relevant, functional characteristics or motifs necessary, or unnecessary for the inhibition of Kv1.3. Thus, while the applicant has support for the specific sequences reduced to practice, they do not have support for the complete genus of variants claimed.
Regarding claim 21, the sequences reduced to practice by the applicant are not representative of the entire genus of a pharmaceutical composition comprising variants of SEQ ID NO: 1, wherein the variant differs from SEQ ID NO: 1 by up to ten substitutions, insertions or deletions and at least one amino acid in position 7, 8, 9, 10 or 11 of SEQ ID NO: 1 is substituted with an amino acid having a positively charged side chain and/or an amino acid having an aromatic side chain wherein any substitutions or deletions in the variant of SEQ ID NO: 1 are at amino acid positions selected from positions 1-5, 7-11, 13-15, 17-23, 25, 28-31, 33 and 35-37 of SEQ ID NO: 1. Nor, would one of ordinary skill in the art be able to attest to the complete genus’s ability to act as a Kv1.3 ion channel inhibitor; the variant may have substitutions or deletions in the sequence that strip it of its ability to inhibit Kv1.3. Thus, while the applicant has support for the sequences reduced to practice, they do not have support for the complete genus of variants claimed in a pharmaceutical composition.
Allowable Subject Matter
Claims 8-9 and 16-19 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: Ion channel blockers comprising of SEQ ID NO: 10-20.
The closest prior art is Reynaud et al. (Reynaud, S., Ciolek, J., Degueldre, M., Saez, N. J., Sequeira, A. F., Duhoo, Y., Brás, J. L. A., Meudal, H., Cabo Díez, M., Fernández Pedrosa, V., Verdenaud, M., Boeri, J., Pereira Ramos, O., Ducancel, F., Vanden Driessche, M., Fourmy, R., Violette, A., Upert, G., Mourier, G., Beck-Sickinger, A. G., … Gilles, N. (2020). A Venomics Approach Coupled to High-Throughput Toxin Production Strategies Identifies the First Venom-Derived Melanocortin Receptor Agonists. Journal of medicinal chemistry, 63(15), 8250–8264.)
Reynaud et al. developed a venomics approach coupled to high-throughput toxin production [Abstract]. They focused on N-TRTX-Pregia, exhibiting an inhibitory cystine knot (ICK) motif, and N- BUTX-Ptria, a short scorpion-CSaß structure. N-BUTX-Ptria is a variant of instant SEQ ID NO:1, consisting of the first 34 residues [Fig 5]. While N-BUTX-Ptria is a variant of SEQ ID NO:1, it does not have at least one amino acid substituted in positions 7-11.
Reynaud states that N-BUTX-Ptria, close in sequence to potassium channel toxins, possesses a dyad composed of a basic and an aromatic residue [Discussions and Conclusions pgh7]. The dyad is stated as essential for potassium activity, but Reynaud shows that it not sufficient for N-BUTX-Ptria to bind potassium channels. While Reynaud et al. produced negative results for binding to potassium channels, they did show that N-BUTX-Ptria had affinity for melanocortin receptors [Discussions and Conclusions pgh7]. The authors also say that they "perhaps did not incubate enough time as the toxins display low affinities and may need a longer time to bind the receptor" [Discussion and Conclusions pgh 8]. This incongruity would motivate one of ordinary skill in the art to start from the variant N-BUTX-Ptria , when looking for toxin-derived Kv1.3 inhibitors. While Reynaud does motivate one of ordinary skill in the art to test the variant N-BUTX-Ptria’s ability to inhibit Kv1.3 again, it does not explicitly teach the claimed SEQ ID NO:10-20, nor any motivation to perform alterations that would help one of ordinary skill in the art arrive to the sequences.
Furthermore, the applicant has reduced to practice SEQ ID NOs: 10-20 and therefore has shown written description support for possession and efficacy of the Kv1.3 inhibitors. Thus, SEQ ID NO: 10-20 are free of prior art and allowable subject matter.
Summary
Claims 1-7 and 21 are rejected under 35 U.S.C. 112(a). Claims 8-9 and 16-19 are objected to due to dependency on a rejected base claim.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SACHI JAUHARI whose telephone number is (571)272-3769. The examiner can normally be reached Mon-Fri 9-4.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached at (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SACHI JAUHARI/Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654
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