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 .
DETAILED ACTION
The amendment filed 10/02/2025 has been entered. Claims 2-4 are cancelled. Claims 11 and 12 are newly added. Claims 1, and 5-12 are pending and under examination.
Response to Arguments
The rejection of claims 1, 7, 9, and 10 under 35 USC 102, and the rejection of claim 8 under 35 USC 103, have been withdrawn in view of Applicant’s amendment, as the prior art references do not teach the treatment of sepsis or lung inflammation by administration of the TAFA4 polypeptide.
With respect to the rejection of claims 1 and 5-10 under 35 USC 112(a), Applicant's arguments filed 10/02/2025 have been fully considered but they are not persuasive. Applicant argues that the disclosure is enabling for a method of treating sepsis or lung inflammation caused by viral infection because administration of LPS (lipopolysaccharide) is a classical model for sepsis. However, LPS, or endotoxin, is a structural component of the cell wall of gram-negative bacteria. LPS is not found in viruses. Therefore, while administration of LPS may be a model for bacterial sepsis, there is no evidence to support that it is a model for viral sepsis. Applicant argues that the disclosure is enabling for treating lung inflammation because TAFA4 inhibits inflammatory cytokine secretion in PBMCs (peripheral blood mononuclear cells) from COVID-19 patients. However, PMBCs are not a model for lung inflammation, nor are there any studies in the instant disclosure that discuss the effects of TAFA4 administration on lung inflammation. The data shown only indicates that TAFA4 may decrease inflammatory cytokine production in an in vitro cell model. Therefore, Applicant’s arguments are not considered persuasive.
Claim Objections
Claim 12 is objected to because of the following informalities: “Virus” should be amended to “viral”. The word “an” should be added before “adeno-associated” so that the claim recites: an adeno-associated viral (AAV) vector.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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.
Scope of Enablement
Claims 1 and 5-12 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 a method of treating bacterial sepsis by administering to the subject a therapeutically effective amount of a TAFA4 polypeptide or nucleic acid molecule thereof, does not reasonably provide enablement for a method of or nucleic acid thereof. 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.
Per MPEP 2164.01(a), the following eight factors should be considered when determining whether the person of ordinary skill in the art would face undue experimentation to make and/or use the invention: (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. While it is not essential that every factor be examined in detail, those factors deemed most relevant should be considered.
Nature of the Invention: Claim 1 is drawn to a method of treating an inflammatory disease in a subject comprising administering to the subject a therapeutically effective amount of a TAFA4 polypeptide or a nucleic acid molecule encoding thereof, wherein the inflammatory disease is sepsis or lung inflammation caused by a viral infection. Claim 5 recites that the viral infection causes severe acute respiratory syndrome. Claim 6 limits the viral infection to Covid-19. Claim 7 recites that the TAFA4 polypeptide comprises a sequence having at least 90% sequence identity to SEQ ID NO:1. Claim 8 recites that the TAFA4 polypeptide is fused to an immunoglobulin constant domain. Claim 9 recites that the nucleic acid molecule is inserted into a suitable vector. Claim 10 recites that the TAFA4 polypeptide or nucleic acid encoding the TAFA4 polypeptide is administered with another active agent used for the treatment of inflammatory disease. Claim 11 limits the suitable vector to a viral vector. Claim 12 limits the viral vector to adeno-associated virus (AAV) vector.
Breadth of the Claims: Independent claim 1 is specific to treating sepsis or lung inflammation caused by a viral infection.
State of the Prior Art and Unpredictability:
Petersen et al., (WO 2006/013462 A2) teaches that the human NsG28 polypeptide is TAFA4 (Page 109, SEQ ID NOs:2-5), and teaches a method of treating neurological diseases, such as Alzheimer’s disease, multiple sclerosis, and ataxia (Page 28, line 29; Page 29, lines 17-32) comprising administering to an individual in need thereof a therapeutically effective amount of an NsG28 polypeptide or an isolated nucleic acid sequence thereof (Page 6, lines 20-23). Petersen teaches that NsG28 polynucleotides may be used to treat conditions or diseases where neural growth, proliferation, differentiation, function, survival, and/or regeneration is desirable, and teaches that NsG28 is preferentially expressed in the human nervous system (Page 71, Paragraph 1). Petersen teaches that NsG28 may act on cell types that are present in the nervous system (Page 71, Paragraphs 2-4).
Kambrun et al., 2018 (TAFA4 Reverses Mechanical Allodynia through Activation of GABAergic Transmission and Microglial Process Retraction) teaches that animals injected with TAFA4 in the spinal cord showed a significant decreased in neuronal discharge following exposure to the Complete Freund’s Adjuvant (CFA) (Page 2889, Column 2, Paragraph 2), which is a noxious stimulus used to induce inflammation and pain. Kambrun also teaches that intrathecal injection of TAFA4 in animals exposed to CFA partially reversed the dramatic decrease in paw withdrawal threshold within 1-hour (Page 2890, Paragraph spanning columns 1 and 2). These results demonstrate that administration of the TAFA4 chemokine results in pain alleviation in animals with inflammation (Page 2893, Column 1).
In summary, the prior art teaches that TAFA4 may be administered to treat inflammatory conditions of the nervous system, however, no prior art references teach methods of treating inflammatory diseases that are not of the nervous system, such as sepsis or inflammatory lung diseases caused by viral infections, by administering only the TAFA4 polypeptide.
Guidance in the Specification and Working Examples: The specification discloses only one in vivo experiment (Figure 3), in which mice were injected with both lipopolysaccharide (LPS) and TAFA4 as a model for bacterial sepsis. Mice injected with TAFA4 in combination with LPS had increased survival compared with mice injected with LPS alone (Figure 3). The specification also discloses that Applicant performed in vitro experiments in which human macrophages or peripheral blood mononuclear cells were exposed to TAFA4 (Figures 1, 2, 4 and 5). In summary, the specification does not provide any working examples in which subjects with lung inflammation or sepsis caused by viral infection were successfully treated via administration of only the TAFA4 polypeptide.
Amount of Experimentation Necessary: Based on Applicant’s disclosure and the lack of predictability in the state of the art prior to the effective filing date of the claimed invention, the person of ordinary skill would have faced undue experimentation. The person of ordinary skill would have had to determine the effective amount of TAFA4 polypeptide to be administered to a subject with lung inflammation or sepsis caused by viral infection, and would have had to determine the most effective mode of administration.
Therefore, based on the above analysis, undue experimentation would be required by the artisan of ordinary skill to practice the claimed invention. Thus, the claims are not fully enabled by the disclosure.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RACHEL EMILY MARTIN whose telephone number is (703)756-1416. The examiner can normally be reached M-Th 8:30-16:00, F 8:30-10:00 EST.
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, Louise Humphrey can be reached at (571) 272-5543. 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.
/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/RACHEL EMILY MARTIN/Examiner, Art Unit 1657