DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Amendment after Non-final office action filed on 7/22/2026 is acknowledged.
3. Claim filed on 7/22/2026 is acknowledged.
4. Claims 1-76, 79-81, 83, 92, 101 and 102 have been cancelled.
5. Claims 77, 78, 82, 84-91 and 93-100 are pending in this application.
6. Claims 85-91 and 97-100 remain withdrawn from consideration pursuant to 37 CFR 1.142(b), as being drawn to non-elected inventions, there being no allowable generic or linking claim.
7. Applicant elected without traverse of Group 2 (claims 76-84, 93 and 94) and elected without traverse of a pharmaceutical composition consisting essential of a protein comprising the amino acid sequence of SEQ ID NO: 29 in a reduced state, water and sodium chloride as species of pharmaceutical composition in the reply filed on 6/18/2025 is acknowledged. Since the elected species of pharmaceutical composition is a subgenus, not a species, the Examiner telephoned Applicant’s representative, Sangil Lee, on 6/30/2025; and Applicant’s representative states on the phone that a pharmaceutical composition in a solution form consisting essential of a protein consisting of the amino acid sequence of SEQ ID NO: 29 in a reduced state, water and sodium chloride as the elected species of pharmaceutical composition (see PTO-413 dated 7/3/2025).
Please note: A pharmaceutical composition in a solution form consisting essential of a protein consisting of the amino acid sequence of SEQ ID NO: 29 in a reduced state, water and sodium chloride as the elected species of pharmaceutical composition as the elected species of pharmaceutical composition does not read on any claim in the elected Group 2. Therefore, it would not be searched and examined in the current office action.
Restriction requirement was deemed proper and made FINAL in the previous office actions. Group 2 is drawn to a pharmaceutical composition consisting of: a) a protein or peptide comprising a thioredoxin monocysteinic active site in a reduced state; and b) a diluent, wherein the diluent is sterile water, isotonic saline, hypertonic saline, phosphate-buffered saline (PBS), or combinations thereof. A search was conducted on the genus in claim 78; and prior art was found. Claims 77, 78, 82, 84 and 93-96 are examined on the merits in this office action.
Withdrawn Rejections
8. Rejection to claims 78, 82, 84, 93, 94, 96 and 102 under 35 U.S.C. 102(a)(1) as being anticipated by Heifetz (US 2016/0230149 A1, filed with IDS) is hereby withdrawn in view of Applicant's amendment to the claim and Applicant’s persuasive arguments.
9. Rejection to claims 77, 78, 82, 84, 93-96 and 102 under 35 U.S.C. 103 as being unpatentable over Heifetz (US 2016/0230149 A1, filed with IDS) in view of Yodoi (EP 0853088 A2, filed with IDS), and as evidenced by the Difference between isotonic saline and normal saline document (from Google, 2025, page 1, cited and enclosed in the previous office action) is hereby withdrawn in view of Applicant's amendment to the claim and Applicant’s persuasive arguments.
10. Rejections to claims 77, 78, 82, 84, 93-96 and 102 on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-17 of US patent 9168290 B2, claims 1-14 of US patent 12390511 B2, claims 43-56 of co-pending Application No. 18/733200, and claims 1-54 of co-pending Application No. 19/292329; and in view of Heifetz (US 2016/0230149 A1, filed with IDS) and Yodoi (EP 0853088 A2, filed with IDS) are hereby withdrawn in view of Applicant's amendment to the claim and Applicant’s persuasive arguments.
Maintained/Revised Rejections
Claim Rejections - 35 U.S.C. § 102(a)(1)
11. 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.
12. (Revised due to Applicant’s amendment to the claim) Claims 77, 78, 82, 84 and 93-96 remain rejected under 35 U.S.C. 102(a)(1) as being anticipated by Falk et al (Pediatric Pulmonology, 2016, 51, pages 292-293, filed with IDS).
The instant claims 77, 78, 82, 84 and 93-96 are drawn to a pharmaceutical composition consisting of: a) a protein or peptide comprising a thioredoxin monocysteinic active site in a reduced state; and b) a diluent, wherein the diluent is sterile water, isotonic saline, hypertonic saline, phosphate-buffered saline (PBS), or combinations thereof.
Falk et al teach ORP-100S having the tradename Theradux (a human thioredoxin variant) exhibits increasing disulfide-reducing activity; and a pharmaceutical composition comprising Theradux (ORP-100S) for treating human cells, wherein DTT is used as positive control and PBS is used as negative control, for example, the whole document. Therefore, in view of the teachings of Falk et al as a whole, one of ordinary skilled in the art would reasonably understand and immediately envision a pharmaceutical composition consisting of Theradux (ORP-100S) and PBS that is suitable for oral administration to a patient, wherein Theradux (ORP-100S) in such pharmaceutical composition is in reduced state. And as evidenced by instant specification, the protein of instant SEQ ID NO: 29 is identical to Theradux (ORP-100S) in Falk et al (see page 20, the 2nd paragraph of instant specification). Therefore, the pharmaceutical composition consisting of Theradux (ORP-100S) in a reduced state and PBS in Falk et al meets the limitations of instant claims 77, 78, 84 and 93-96.
With regards to the limitation recited in instant claim 82, in the instant case, Theradux (ORP-100S) in reduced state in Falk et al is identical to a protein consisting of the amino acid sequence of instant SEQ ID NO: 29 in a reduced state and meets all the structural limitations of the protein or peptide recited in instant claim 78. Therefore, Theradux (ORP-100S) in reduced state in Falk et al would necessarily have the same properties and functionality of a protein consisting of the amino acid sequence of instant SEQ ID NO: 29 in a reduced state and/or the protein or peptide recited in instant claim 78. Thus, Theradux (ORP-100S) in reduced state in Falk et al is operable to activate one or more endogenous antimicrobial peptides, wherein the activation results in a therapeutically effective reagent to treat or prevent infectious diseases. Furthermore, the MPEP states: “Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) (see MPEP § 2112.01 II). And, since the USPTO lacks the experimental facilities to make a further determination, the burden is on the Applicant to prove the otherwise.
Since the reference teaches all the limitations of instant claims 77, 78, 82, 84 and 93-96; the reference anticipates instant claims 77, 78, 82, 84 and 93-96.
Response to Applicant's Arguments
13. Applicant argues that “Falk does not disclose the composition of the Theradux (1 mM) formulation used in the experiment. In particular, Falk does not disclose that the Theradux formulation consists only of a protein or peptide comprising a thioredoxin monocysteinic active site in a reduced state and a diluent selected from sterile water, isotonic saline, hypertonic saline, phosphate-buffered saline (PBS), or combinations thereof.”
14. Applicant's arguments have been fully considered but have not been found persuasive.
In response to Applicant's arguments about instant rejection, the Examiner understands that Falk et al do not explicitly state the pharmaceutical composition comprising Theradux (ORP-100S) used in the experiment is one consisting of Theradux and PBS. However, in the instant case, as stated in Section 12 above, Falk et al teach a pharmaceutical composition comprising Theradux (ORP-100S) for treating human cells, wherein DTT is used as positive control and PBS is used as negative control. And it is well known in the drug development art and/or the art of best practices for designing biology experiments, the solvent used to dissolve the drug (vehicle) is used as a negative control so that one can determine whether the observed effects are due to the drug or the solvent, as discussed in BioFord Research Team (Positive vs Negative Controls in Experiments: Examples and Best Practices, 2026, pages 1-16, from https://bioford.ai/blog/positive-negative-controls-experiments, see for example, pages 4-5, Section “What Is a Negative Control?”) and many others. Therefore, in the instant case, considering the state of art regarding drug development and/or best practices for designing biology experiments and in view of the teachings of Falk et al as a whole, one of ordinary skilled in the art would reasonably understand and immediately envision the pharmaceutical composition comprising Theradux (ORP-100S) used in the experiment in Falk et al a pharmaceutical composition consisting of Theradux (ORP-100S) and PBS that is suitable for oral administration to a patient, wherein Theradux (ORP-100S) in such pharmaceutical composition is in reduced state. Thus, Falk et al teach all the limitations of instant claims 77, 78, 82, 84 and 93-96; and the rejection is deemed proper and is hereby maintained.
The BioFord Research Team reference is cited only for the purpose of rebutting Applicant's arguments, therefore, it is not cited as a prior art reference.
Obviousness Double Patenting
15. 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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
16. (Revised due to Applicant’s amendment to the claim) Claims 77, 78, 82, 84 and 93-96 remain provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1, 3-7, 18 and 19 of co-pending Application No. 18/349112 in view of Falk et al (Pediatric Pulmonology, 2016, 51, pages 292-293, filed with IDS).
17. The instant claims 77, 78, 82, 84 and 93-96 are drawn to a pharmaceutical composition consisting of: a) a protein or peptide comprising a thioredoxin monocysteinic active site in a reduced state; and b) a diluent, wherein the diluent is sterile water, isotonic saline, hypertonic saline, phosphate-buffered saline (PBS), or combinations thereof.
18. Claims 1, 3-7, 18 and 19 of co-pending Application No. 18/349112 are drawn to various treatment methods of administering an effective amount of a composition comprising a monocysteinic thioredoxin, wherein the monocysteinic thioredoxin is a protein or peptide comprising an amino acid sequence that is at least 85% identical to SEQ ID NO: 1 or 2, wherein the N-terminal methionine residue is optionally not present, wherein the sequence optionally comprises one or more post-translational modifications, and wherein for SEQ ID NO:1, X represents a residue of any amino acid other than cysteine; and a composition comprising a monocysteinic thioredoxin formulated for administration by a route selected from the group consisting of intravenous infusion, subcutaneous injection, intramuscular injection, intraperitoneal injection, and topical inhalation, wherein the monocysteinic thioredoxin is a protein or peptide comprising SEQ ID NO: 1 or 2, wherein the N-terminal methionine residue is optionally not present, wherein the sequence optionally comprises one or more post-translational modifications, and wherein for SEQ ID NO:1, X represents a residue of any amino acid other than cysteine.
In view of the combined teachings of claims 1, 3-7, 18 and 19 of co-pending Application No. 18/349112, it would have been obvious to one of ordinary skilled in the art to develop a pharmaceutical composition comprising a protein or peptide comprising SEQ ID NO: 2 (as a monocysteinic thioredoxin) in a reduced state and a pharmaceutically acceptable excipient, wherein the pharmaceutical composition is formulated for administration by a route selected from the group consisting of intravenous infusion, subcutaneous injection, intramuscular injection, intraperitoneal injection, and topical inhalation.
The protein of SEQ ID NO: 2 recited in claims of co-pending Application No. 18/3491122 is identical to the protein of instant SEQ ID NO: 29.
19. The difference between the pharmaceutical composition developed from the combined teachings of claims 1, 3-7, 18 and 19 of co-pending Application No. 18/349112 above and the pharmaceutical composition recited in instant claims 77, 78, 82, 84 and 93-96 is that it does not teach the limitations recited in instant claims.
However, in view of the teachings of Falk et al as set forth in Section 12 above, it would have been obvious to one of ordinary skilled in the art to modify the pharmaceutical composition developed from the combined teachings of claims 1, 3-7, 18 and 19 of co-pending Application No. 18/349112 above and develop the pharmaceutical composition recited in instant claims 77, 78, 84 and 93-96.
With regards to the limitation recited in instant claim 82, in the instant case, the protein of SEQ ID NO: 2 in reduced state recited in claims of co-pending Application No. 18/349112 is identical to the protein consisting of the amino acid sequence of instant SEQ ID NO: 29 in a reduced state and meets all the structural limitations of the protein or peptide recited in instant claim 78. Therefore, the protein of SEQ ID NO: 2 in reduced state recited in claims of co-pending Application No. 18/349112 would necessarily have the same properties and functionality of the protein consisting of the amino acid sequence of instant SEQ ID NO: 29 in a reduced state and/or the protein or peptide recited in instant claim 78. Thus, the protein of SEQ ID NO: 2 in reduced state recited in claims of co-pending Application No. 18/349112 is operable to activate one or more endogenous antimicrobial peptides, wherein the activation results in a therapeutically effective reagent to treat or prevent infectious diseases. Furthermore, the MPEP states: “Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) (see MPEP § 2112.01 II). And, since the USPTO lacks the experimental facilities to make a further determination, the burden is on the Applicant to prove the otherwise.
This is a provisional obviousness-type double patenting rejections because the conflicting claims have not in fact been patented.
20. (Revised due to Applicant’s amendment to the claim) For the same/similar reasoning/rational as the rejection set forth in Sections 16-19 above, instant claims 77, 78, 82, 84 and 93-96 remain provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1 and 3-5 of co-pending Application No. 18/349113, and claims 1-12 of co-pending Application No. 18/349114; and in view of the teachings of Falk et al (Pediatric Pulmonology, 2016, 51, pages 292-293, filed with IDS) as set forth in Section 12 above.
These are all provisional obviousness-type double patenting rejections because the conflicting claims have not in fact been patented.
Response to Applicant's Arguments
21. Applicant argues that “The claims of any of the cited co-pending applications and patents are not directed to a pharmaceutical composition consisting of a protein or peptide comprising a thioredoxin monocysteinic active site in a reduced state, and a diluent selected from sterile water, isotonic saline, hypertonic saline, phosphate-buffered saline (PBS), or combinations thereof.” Applicant further discussed the novel formulation strategy disclosed in instant specification and argues that “This novel thioredoxin formulation strategy is not taught by Falk, Heifetz and Yodoi, as discussed above. There would be no motivation to formulate a composition containing a protein
or peptide comprising a thioredoxin active site in a reduced state without using any stabilizing agents such as reducing sugars and EDTA to arrive at the claimed composition”
22. Applicant's arguments have been fully considered but have not been found persuasive.
Please note: Since none of the maintained ODP rejections is based on further in view of Heifetz and Yodoi, Applicant’s arguments related to such references are moot.
In response to Applicant’s arguments about these ODP rejections, the Examiner understands that the claims of any of these co-pending applications are not directed to a pharmaceutical composition consisting of a protein or peptide comprising a thioredoxin monocysteinic active site in a reduced state, and a diluent selected from sterile water, isotonic saline, hypertonic saline, phosphate-buffered saline (PBS), or combinations thereof. However, in the instant case, the Examiner would like to point out that all these ODP rejections are based on further in view of the teachings of Falk et al as set forth in Section 12 above. And as stated in Section 12 above, Falk et al teach a pharmaceutical composition consisting of a protein consisting of the amino acid sequence of instant SEQ ID NO: 29 in a reduced state and PBS. Therefore, it would have been obvious to one of ordinary skilled in the art to formulate a composition consisting of a protein or peptide comprising a thioredoxin active site in a reduced state and PBS. Thus, these double patenting rejections are deemed proper. And until a proper terminal disclaimer is filed and approved by the Office, these double patenting rejections are hereby maintained.
Conclusion
THIS ACTION IS MADE FINAL. 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.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LI N KOMATSU whose telephone number is (571)270-3534. The examiner can normally be reached Mon-Fri 8am-4pm EST.
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/LI N KOMATSU/Primary Examiner, Art Unit 1658
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