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 Claims
The amendments and arguments filed on 5/11/2026 are acknowledged and have been fully considered. Claims 1-13 are now pending. No claims are canceled; claims 1 and 8 are amended; no claims are withdrawn; no claims are new.
Claims 1-13 will be examined on the merits herein.
Objections/Rejections Withdrawn
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied, and constitute the complete set presently being applied to the instant application.
Allowable Subject Matter
Claim 8 is 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.
Specifically, the prior art does not reasonably teach the method of treating post COVID-19 syndrome in a subject comprising administering TEKKRRETVERKEKE (SEQ ID NO: 1). SEQ ID NO: 1 is supported by specification, fully enabled and free of prior art.
Claim Rejections - 35 USC § 112 (modified)
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 9-13 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.
MPEP § 2163 states that 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, 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.
Scope of the claims
The claims are drawn to a method of treating post COVID-19 syndrome in a subject, comprising administering to the subject a compound selected from the group consisting of Ezrin peptide 1 consisting of the amino acid sequence NH2_Thr-Glu-Lys-Lys-Arg-Arg- Glu-Thr-Val-Glu-Arg-Glu-Lys-Glu_COOH (SEQ ID NO: 1), the analogue of Ezrin peptide 1 of the formula (I) and combinations of Ezrin peptide 1 and the analogue of Ezrin peptide 1 of the formula (I), NH2_ X1-Glu-Lys-Lys-Arg-Arg-Glu-Thr-Val-Glu-Arg-Glu-X2-X3_COOH (I) where X1, X2 and X3 are identical or different and are non-polar amino acid residues.
Actual Reduction to Practice
MPEP § 2163 states that 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. 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.
In the instant case, several embodiments of the invention were reduced to practice: The analogues of Ezrin peptide 1 are tetradecapeptides, which are of the following general formula:NH2_X1-Glu-Lys-Lys-Arg-Arg-Glu-Thr-Val-Glu-Arg-Glu-X2-X3_COOH (I)
where X1, X2 and X3 are identical or different and are non-polar amino acid residues, where the amino acids are in particular selected from the group consisting of glycine, alanine, valine, leucine, methionine, isoleucine, proline, phenylalanine, tryptophan and combinations thereof. A particular example of such an analogues of Ezrin peptide 1 is the compound of formula (I), where X1, X2 and X3 are glycine residues, i.e. the compound of sequence ID No. 2: GEKKRRETVERKEGG or NH2_Gly-Glu-Lys-Lys-Arg-Arg-Glu-Thr-Val-Glu-Arg-Glu-Gly-Gly_COOH (SEQ ID NO:2), respectively (see page 5, line 28-32 through page 6, line 1-6).
The specification states that analogues of Ezrin peptide 1 of the formula (I) as described or pharmaceutical compositions comprising such an analogue of Ezrin peptide 1 and at least one pharmaceutically acceptable carrier are suitable for the treatment of the post-COVID-19 syndrome. The inventors have also found out that combinations of Ezrin peptide 1 and an analogue of Ezrin peptide 1 of the formula (I) as described herein, as well as pharmaceutical compositions comprising a combination of Ezrin peptide 1 and an analogue of Ezrin peptide 1 of the formula (I) as described herein and at least one pharmaceutically acceptable carrier are suitable for the treatment of the post-COVID-19 syndrome (page 4, line 24-32).
Therefore, the instant specification has failed to meet the written description requirement by actual reduction to practice of a representative number of species alone.
Sufficient relevant identifying characteristic
MPEP § 2163 states that 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, 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 thereof.
i. Structure:
As stated above, the complete structure of the peptide analogues are not disclosed. As there are no positional limitations on where modifications can occur, this allows for more than a large number of possible variants where only 3 substitutions of amino acids X1, X2 and X3 occur. There are identical or different and are non-polar amino acid residues, where the amino acids are in particular selected from the group consisting of glycine, alanine, valine, leucine, methionine, isoleucine, proline, phenylalanine, tryptophan and combinations thereof.
ii. Physical and/or chemical properties:
The data presented in the specification raise more questions about the physical properties of the genus than they answer. The data do not suggest the physical basis for the peptide derivatives and therefore do not describe which substitutions, deletions or additions could be made while preserving this conformation. Understanding the physical basis for having antimicrobial activity is critical to determining which of the sequences that meet the sequence requirements of the genus also meet this additional functional requirement of the genus.
iii. Functional characteristics when coupled with a known or disclosed correlation between function and structure:
The specification does not describe a general correlation between sequence and structural coordinates for the claimed genus. As a result, it is impossible to predict, based on the specification, how changing any amino acid residue in the peptide analogue sequence will improve lingering symptoms of post-COVID-19 syndrome.
iv. Method of making the claim invention
Solid-phase peptide synthesis of the peptide analogue variants is well-known in the art. It is not disputed that one of ordinary skill in the art could isolate, albeit with route experimentation and optimization, a peptide of a given sequence provided that the sequence is known. Where the specification fails to provide description is in the structure of the peptide to make. For all of the reasons presented above, one of ordinary skill in the art would not know which of the countless peptides that meet the sequence requirements of the claims would also have specific structural conformation with expected to reduce long-term COVID-19-related symptoms. In other words, the specification does not describe which peptides to make.
Conclusion
For these reasons, the skilled artisan would not reasonably conclude that the inventor(s), at the time the application was filed, had possession of the full scope of the claimed invention.
Response to Arguments
Applicant's arguments filed 5/11/2026 have been fully considered but they are not persuasive in view of the modified grounds of rejected necessitated by amendment.
Applicant argues that claims 1-13 were rejected under 35 U.S.C. 112 as allegedly failing to comply with the written description requirement and as allegedly not being fully enabled. While not acquiescing to these rejections, Applicant believes that the amendments to the claims 1 and 8 obviate these rejections.
By amending claims 1 and 8 from “comprising” to “consisting of” , the applicant has narrowed down the scope of the claims. However, as set forth in the rejections of record in the office action mailed 2/11/2026, the administered peptide analogue/variant also has issues under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph that is not overcome by the amendment. .Claims 1-7 and 9-13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating post COVID-19 syndrome, does not reasonably provide enablement for treating long-term COVID-19-related symptoms broadly. 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.
The Applicant’s attention is drawn to In re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set forth eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
1) The nature of the invention; 2) the state of the prior art; 3) the relative skill of those in the art; 4) the predictability or unpredictability of the art; 5) the breadth of the claims; 6) the amount of direction or guidance presented; 7) the presence or absence of working examples; and 8) the quantity of experimentation necessary.
1) Nature of the invention and 5) breadth of the claims: The claims are drawn to a
method of treating post COVID-19 syndrome in a subject, comprising administering to the subject a compound selected from the group consisting of Ezrin peptide 1 consisting of the amino acid sequence NH2_Thr-Glu-Lys-Lys-Arg-Arg- Glu-Thr-Val-Glu-Arg-Glu-Lys-Glu_COOH (SEQ ID NO: 1), the analogue of Ezrin peptide 1 of the formula (I) and combinations of Ezrin peptide 1 and the analogue of Ezrin peptide 1 of the formula (I).
2) State of the prior art and 4) predictability or unpredictability of the art: The art at the
time of filing indicated that the peptide TEKKRRETVEREKE was developed by Holms et al. (WO 95/33768, published 12/14/1995, filed with IDS dated 7/29/2024) as a treatment for AIDS. This disclosure does not provide any insight that would lead one of ordinary skill in the art to use this peptide for COVID-19 treatment. Holms (Immuno 2.2: 260-282. (2022), filed with IDS dated 10/24/2024) describes a possible mechanism of the claimed peptide against COVID-19: “Intravenous-VIP and spray-inhaled Human Ezrin Peptides appear to stop COVID-19 by related mechanisms of action. Human Ezrin Peptides (HEPs) such as HEP-1 and RepG3, and Vaso-active-Intestinal Peptide (VIP), appear to have a related anti-inflammatory and anti-COVID-19 activity by triggering PKA>CREB activation and inhibiting NFκB-mediated pro-inflammatory cytokine expression. However, this mechanism is still speculative and much more work needs to be done.” (Holms, Immuno (2022), page 278, para. 4, filed with IDS dated 10/24/2024) This mechanism is not conclusive, and it is unpredictable whether the claimed method could effectively treat post COVID-19 syndrome in a subject.
Millet et al. (PLoS One 7.11: e49566 (2012) , filed with IDS dated 7/29/2024) describes how some regions of the Ezrin protein interact with SARS Coronavirus spike proteins, but this disclosure focuses on the FERM domain of the Ezrin protein: “The fact that the replication level measured by qRT-PCR was slightly lower in the clone expressing the FERM domain of ezrin than control cells at 24 hours post-infection (Fig. 7B) suggests that although ezrin restricts the rate of infection at early time points, its function may be important for later stages. The presently claimed method utilizes a peptide whose sequence is not from the FERM domain of Ezrin.” (Millet et al., page 9, col. 2, para. 3, filed with IDS dated 7/29/2024).
3) The relative skill of those in the art: The relative skill of those in the art is high.
6) The amount of direction or guidance presented: At the time of filing, no direction or
guidance was presented in either the prior art or the instant specification that would enable one to administer a composition comprising SEQ ID NO: 1 analogue variants in addition to the other compositions to treat post COVID-19 syndrome broadly as intended by the claims.
7) The presence or absence of working examples and 8) The quantity of experimentation necessary: Applicant provides an examples using a single peptide SEQ ID NO: 1 (TEKKRRETVEREKE) administered to several subjects. This peptide is certainly enabled. However, the current claims encompass much larger number of structures, the peptide analogue variants with additional unpredictable results. The open-ended nature of the claims would create a tremendous amount of experimentation to make and test all encompassed peptides.
Therefore, in view of the Wands factors, as discussed above, Applicants fail to provide information sufficient to practice the claimed invention for the treatment of post COVID-19 syndrome broadly.
Response to Arguments
Applicant's arguments filed 5/11/2026 have been fully considered but they are not persuasive in view of the modified grounds of rejected necessitated by amendment.
Applicant argues that claims 1-13 were rejected under 35 U.S.C. 112 as allegedly failing to comply with the written description requirement and as allegedly not being fully enabled. While not acquiescing to these rejections, Applicant believes that the amendments to the claims 1 and 8 obviate these rejections.
While applicant has narrowed down the scope of the claim by amending claims 1 and 8 from “comprising” to “consisting of”, the scope of the method of treating post COVID-19 syndrome in a subject, comprising administering to the subject a compound selected from the group, still encompasses “administering peptide analogue/s” which is rejected for reasons indicated above.
In response to applicant’s argument that the examiner has explained the written enablement requirement for a claimed genus; and the peptide analogues claimed here cannot be readily computed. Given this unpredictability of protein design, the skilled artisan would not have been in possession of the substantial repertoire of peptide species encompassed by the claimed invention and would conclude that the specification fails to disclose a representative number of species to describe the claimed genus. See MPEP § 2164.01.
Double Patenting (modified)
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 1-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 12,629,405 B2 (US‘405)( Date Published 05/19/2026). Note that this rejection was presented as a provisional rejection over Application No. 17/915,847 in the Non-Final Office Action mailed, 2/11/2026. As the Application has issued as a patent, the rejection is no longer provisional. Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
Claim 1 of US‘405 recites a method of treating COVID-19 or post COVID-19 syndrome in a subject, comprising administering to the subject Ezrin peptide 1, wherein the Ezrin peptide 1 consists of the amino acid sequence NH2_Thr-Glu-Lys-Lys-Arg-Arg-Glu-Thr-Val-Glu-Arg-Glu-Lys-Glu_COOH (SEQ ID NO:1). Claim 9 of US‘405 recites a method of treating COVID-19 or post COVID-19 syndrome in a subject, comprising administering to the subject an analogue of Ezrin peptide 1, wherein the analogue consists of the formula (I) TABLE-US-00002 (I) (SEQ ID NO: 5) NH2_X1-Glu-Lys-Lys-Arg-Arg-Glu-Thr-Val-Glu-Arg-Glu- X2-X3_COOH where X1, X2 and X3 are identical or different and are non-polar amino acid residues. Claim 15 of US’405 teaches the method, wherein the subject is a human tested positive for SARS-COV-2 or suspected of being infected with SARS-COV-2. Therefore, US‘405 claim anticipate instant claim 1.
Claim 9 of US‘405 recites a method of treating COVID-19 or post COVID-19 syndrome in a subject, comprising administering to the subject an analogue of Ezrin peptide 1, wherein the analogue consists of the formula (I) TABLE-US-00002 (I) (SEQ ID NO: 5) NH2_X1-Glu-Lys-Lys-Arg-Arg-Glu-Thr-Val-Glu-Arg-Glu- X2-X3_COOH where X1, X2 and X3 are identical or different and are non-polar amino acid residues. Claim 17 of US’405 teaches the method wherein the analogue of Ezrin peptide 1 is administered in a pharmaceutical composition comprising the analogue of Ezrin peptide 1, or in combination with Ezrin peptide 1 consisting of the amino acid sequence NH2 Thr-Glu-Lys-Lys-Arg-Arg-Glu-Thr-Val-Glu-Arg-Glu-Lys-Glu COOH (SEQ ID NO: 1), and a pharmaceutically acceptable carrier. Therefore, US‘405 claims anticipate instant claim 11.
Regarding claim 2, US‘405 claim 2 recites saline solution for subcutaneous administration.
Regarding claim 3, US‘405 claim 3 recites formulated for oral administration.
Regarding claim 4, US‘405 claim 4 recites formulated for inhalation or for intranasal administration.
Regarding claim 5, US‘405 claim 5 recites administered daily.
Regarding claims 6 and 7, US‘405 specifies Ezrin peptide1 and its analogues are administered to an adult human in an amount of at least 0.1 mg per day, in particular at least 0.2 mg per day, e.g. in an amount of at least 0.5 mg per day, such as 0.1 to 50 mg per day or 0.2 to 20 mg per day or 0.5 to 10 mg per day. In one embodiment, the Ezrin peptide1 is administered in a dosage in the range of or between about 0.2 and 8 milligrams (mg), preferably 1 to 5 mg, more preferably 2 to 4 mg per day. In another embodiment, the Ezrin peptide1 is administered in a dosage in the range of 0.1 and 5 milligrams per day (mg/d), preferably 0.1 to 4 mg/d, more preferably 0.1 to 1 mg/d, especially 0.1 to 0.5 mg/d. It is also possible to start with higher dosage of e.g. in the range of 1 to 5 mg/d, more preferably 1 to 3 mg/d and then continue with lower dosage of e.g. 0.1 to 0.5 mg/d.
Regarding claim 8, US‘405 claim 1 recites the Ezrin peptide 1 consists of the amino acid sequence NH2_Thr-Glu-Lys-Lys-Arg-Arg-Glu-Thr-Val- Glu-Arg-Glu-Lys-Glu-COOH (SEQ ID NO: 1).
Regarding claim 9, US‘405 claim 9-14 discloses an analogue of Ezrin peptide 1, wherein the analogue consists of the formula (I) TABLE-US-00002 (I) (SEQ ID NO: 5) NH2_X1-Glu-Lys-Lys-Arg-Arg-Glu-Thr-Val-Glu-Arg-Glu- X2-X3_COOH where X1, X2 and X3 are identical or different and are non-polar amino acid residues.
Regarding claim 10, US‘405 claim 16 recites the analogue of Ezrin peptide 1 is used in combination with Ezrin peptide 1.
Regarding claim 12, US‘405 claim 8 recites the composition is formulated either for subcutaneous administration, oral administration, inhalation or intranasal administration.
Regarding claim 13, US‘405 claim 18 recites X1, X2 and X3 are each individually selected from the group of amino acid residues consisting of glycine, alanine, valine, leucine, methionine, isoleucine, proline, phenylalanine, and tryptophan.
Response to Arguments
Applicant argues that claims 1-13 were provisionally rejected on the ground of nonstatutory double patenting as allegedly being unpatentable over claims 1 and 3-19 of Application No. 17/915,847. Applicant has requested that the provisional rejections be held in abeyance until patentable subject matter is identified.
The request to hold the rejection in abeyance has been noted and as no arguments regarding the merits of the rejection have been submitted, the rejection is maintained for reasons of record.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 KOYELI BANERJEE whose telephone number is (571)272-5751. The examiner can normally be reached Monday-Friday 8-4PM.
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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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/KOYELI BANERJEE/Examiner, Art Unit 1658
/Melissa L Fisher/Supervisory Patent Examiner, Art Unit 1658
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