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 .
Applicant's reply to the previous Office action, dated May 4, 2026, has been received. By way of this reply, Applicant has amended the specification and claims 1, 5, 14-15, and 19, cancelled claims 2, 8, 12-13, 17-18, and 21-22, and introduced new claims 23-26.
Claims 1, 5-6, 11, 14-15, 19-20 and 23-26 are pending in the application. Claims 23-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on August 31, 2023.
Claims 1, 5-6, 11, 14-15 and 19-20 are therefore under examination before the Office.
The rejections of record can be found in the previous Office action, dated December 3, 2025.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on May 4, 2026 was filed after the mailing date of the first Office action on the merits on October 17, 2023. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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, 5-6, 11, 14-15 and 19-20 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) 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) (reversing the PTO’s determination that claims directed to methods for detection of hepatitis B surface antigens did not satisfy the enablement requirement). In Wands, the court noted that there was no disagreement as to the facts, but merely a disagreement as to the interpretation of the data and the conclusion to be made from the facts. In re Wands, 858 F.2d at 736-40, 8 USPQ2d at 1403-07. The court held that the specification was enabling with respect to the claims at issue and found that "there was considerable direction and guidance" in the specification; there was "a high level of skill in the art at the time the application was filed;" and "all of the methods needed to practice the invention were well known." 858 F.2d at 740, 8 USPQ2d at 1406. After considering all the factors related to the enablement issue, the court concluded that "it would not require undue experimentation to obtain antibodies needed to practice the claimed invention." Id., 8 USPQ2d at 1407.
Breadth of claims and nature of invention
The present claims are directed to methods of treating a subject with a viral infection by administering a composition to a respiratory system of the subject by inhalation, wherein the composition comprises extracellular matrix (ECM) derived from spleen tissue and ECM derived from lung tissue, wherein the viral infection is a coronavirus, a herpesvirus, or a retrovirus, and wherein the ECM directly contact the virus in the respiratory system. Further claims indicate the claimed method of treatment of SARS-CoV-2, though the independent claims are more broadly drawn to treatment of any coronavirus, herpesvirus, or retrovirus.
State of the art and the level of ordinary skill
As of the effective filing date of April 22, 2020, no treatment for SARS-CoV-2 infection was recognized by the FDA. Nor were any broad-spectrum antivirals known in the art which could treat any coronavirus, herpesvirus, or retrovirus when administered by inhalation. The use of complex materials such as ECM as inhalants were not widely practiced in the field, and not as antivirals.
The level of predictability of the art
Pharmaceutical therapies in the absence of in vivo clinical data are unpredictable for the following reasons; (1) the therapeutic may be inactivated before producing an effect, i.e. such as degradation, immunological inactivation or due to an inherently short half-life of the protein; (2) the therapeutic may not reach the target area because, i.e. the therapeutic may not be able to cross the mucosa or the therapeutic may be adsorbed by fluids, cells and tissues where the protein has no effect; and (3) other functional properties, known or unknown, may make the therapeutic unsuitable for in vivo therapeutic use, i.e. such as adverse side effects prohibitive to the use of such treatment. See page 1338, footnote 7 of Ex parte Aggarwal, 23 USPQ2d 1334 (PTO Bd. Pat App. & Inter. 1992).
For example, according to Mok (Pharmaceutics. 2023 Mar 12;15(3):925 at page 18, second paragraph, cited previously), vitamin D is useful in cell-based assays against SARS-CoV-2, but does not provide a benefit in reducing viral titer in vivo.
The amount of direction provided by the inventor and existence of working examples
The examples performed in Applicant's specification describe only viral inactivation based upon administration of the claimed ECM to viral aliquot in serum-free media. The argument that an in vitro cell culture assay accurately replicates an in vivo treatment is unlikely, especially given the dosages described in the specification of 1 gram of material to 1 milliliter of viral sample. Such a treatment would require multiple kilograms of material, as the human body has about 5 liters of blood alone. This contrasts with the exemplary dosages cited in the specification at page 9 of 1-20 milligrams.
The claims also recite the properties of "directly contact[ing] the virus and inactivat[ing] at least a portion of a virus population of the subject, thereby reducing the viral load of the subject." However, Applicant's specification lacks any in vivo studies which demonstrate that the ECM is capable of coming into direct contact with a virus within a subject. There is no evidence to suggest that the claimed ECM is capable of performing the claimed function in the context of treating a subject that is infected with a virus. No guidance is given in the specification as to how this method may be performed, especially given the scope of viruses encompassed by the claims. There is no evidence to suggest that the claimed ECM is capable of performing the claimed function in the context of treating a subject that is infected with a virus. An ex vivo culture assay cannot accurately replicate in vivo conditions for the purposes of viral inactivation.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure
There is insufficient guidance and direction as well as objective evidence provided for treating the scope of diseases encompassed by the claimed method. In view of the lack of predictability of the art (e.g., treating an viral infection) to which the invention pertains, undue experimentation would be required to practice the claimed method of treatment of any viral infection with a reasonable expectation of success, absent a specific and detailed description in Applicant's specification of how to effectively use the claimed agent and absent working examples providing evidence which is reasonably predictive that the claimed agent is effective for treating any viral infection commensurate in scope with the claimed invention.
There is insufficient guidance and direction as well as objective evidence provided for treating the scope of diseases encompassed by the claimed method. In view of the lack of predictability of the art to which the invention pertains, undue experimentation would be required to practice the claimed method with a reasonable expectation of success, absent a specific and detailed description in Applicant's specification of how to effectively use the claimed agent and absent working examples providing evidence which is reasonably predictive that the claimed agent is effective, commensurate in scope with the claimed invention.
The guidance of the specification must be commensurate with the scope of the claimed invention, i.e., must reasonably enable the full scope of the claimed invention. See Pac. Biosciences of Cal., Inc. V. Oxford Nanopore Techs., Inc., 996 F.3d 1342, 1352, 2021 USPQ2d 519 (Fed. Cir. 2021). MPEP 2164.05. In view of the lack of working examples, the nature of the invention, the unpredictability of the art and the breadth of the claim scope, it would take undue trials and errors to practice the claimed invention.
Applicant argues that the cited examples in the specification provides data for a suitable test material, and that the composition retains native ECM components that have therapeutic efficacy, and in particular, antiviral activity. Applicant further argues that there is no requirement for in vivo studies to comply with enablement, and "a rigorous or an invariable exact correlation [between in vitro or in vivo animal model assays and a disclosed or a claimed method of use] is not required." MPEP § 2164.02(II) (citing Cross v. Iizuka, 753 F.2d 1040, 1050, 224 USPQ 739, 747 (Fed. Cir. 1985)), and that the FDA is currently moving away from in vivo animal testing for monoclonal antibody therapies and other drugs. Applicant also presents a Declaration under 37 CFR 1.132 from inventor Clay Fette ("the Fette Declaration") describing additional in vitro studies for different coronaviruses, herpesviruses, and retroviruses that confirm antiviral activity.
Applicant's arguments have been considered but are not found to be persuasive.
The instant claims are broader than solely the ReyaGel used in Applicant's experiments. As long as the composition comprises extracellular matrix (ECM) derived from spleen tissue and ECM derived from lung tissue, and the ECMs retains native bioactive components of the spleen tissue and/or lung tissue including fibroblast growth factor, vascular endothelial growth factor, and epidermal growth factor, the claim is satisfied.
While inhaled dry powders or aerosols were known in the art to be useful in treating viral infections such as RSV or influenza (see Nainwal, Pulm Pharmacol Ther. 2022 Dec:77:102170), these compounds are small molecules, lacking the complexity of ECM material. It is also noted that the FDA approval for ReyaGel only recites topical uses in wound healing, and is silent with regards to inhalation or any properties arising from such. It is not readily apparent as to how a wound dressing is meant to be used as an inhalant. This adds to the lack of predictability in the art.
Claim 11 further recites that the composition may be in a gel form. It is not clear as to how a gel can be inhaled.
With regards to Applicant's argument concerning changes in FDA approval, the relevant test for patentability is not governed by the FDA, nor is Applicant claiming an antibody. The test is that the ordinary practitioner can perform the claimed method without undue experimentation.
With regards to Applicant's argument concerning the use for in vitro versus in vivo models, there is no established previous antiviral activity for ECM to make such a correlation. The examples recited in the Fette Declaration describe topical application of ReyaGel to cells, or mixtures performed in suspension. At no point was an inhalant test performed. Applicant solely relies upon ex vivo applications of the composition to prove antiviral activity, and then attempts to extrapolate this to an in vivo activity. Even the EpiAirway model described in paragraph 8 of the Fette Declaration does not accurately recapitulate the complexity of lower respiratory tract (see Nainwal at page 2 concerning the mucociliary blanket and alveolar macrophages, as well as the lack of any specific antiviral agent for SARS-CoV-2).
The claims also recite the properties of "directly contact[ing] the virus and inactivat[ing] at least a portion of a virus population of the subject, thereby reducing the viral load of the subject." However, Applicant's specification lacks any in vivo studies which demonstrate that the ECM is capable of coming into direct contact with a virus within a subject. There is no evidence to suggest that the claimed ECM is capable of performing the claimed function in the context of treating a subject that is infected with a virus. No guidance is given in the specification as to how this method may be performed, especially given the scope of viruses encompassed by the claims.
Based upon the scope of the claims, the nature of the invention, the lack of predictability in the art, and the lack of direction provided in the disclosure, Applicant's ex vivo experiments do not provide sufficient guidance as to how the ordinary practitioner may perform the claimed method without undue experimentation.
This rejection is therefore maintained.
Conclusion
No claim is allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER JOHANSEN whose telephone number is (571)272-0280. The examiner can normally be reached Monday-Friday, 7:00 to 3:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at (571) 270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/PETER JOHANSEN/Examiner, Art Unit 1644
Prosecution Insights