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 the Claims
Claims 1-20 were originally filed December 6, 2024.
The amendment received April 18, 2025 added status identifiers only.
The amendment received October 7, 2025 amended claims 1, 3, 14, and 16 and canceled claims 2, 15, and 20.
Claims 1, 3-14, 16-19 are currently pending.
Claims 1, 3, 5, 7, 14, 16, and 18 are currently under consideration.
Election/Restrictions
Applicant elected, without traverse, Group I (claims 1-3, 5-10, 12-16, and 18-20) in the reply filed on April 18, 2025. Claims 4, 11, and 17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected method, there being no allowable generic or linking claim.
Applicant elected, without traverse, preventing viral infection of a cell, LIN28B or fragments thereof, LIN28B binds to Alu retrotransposons, parenteral, and viral infections as the species in the reply filed on April 18, 2025. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Claims 6, 8-10, 12, 13, 19, and 20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species, there being no allowable generic or linking claim.
Please note: preventing viral infection of a cell is a subgenus, LIN28B or fragments thereof is not a single specific species, parenteral is a subgenus, and viral infections is a subgenus. In order to advance prosecution, the elections have been accepted. However, this does not preclude a future species requirement particularly if the claims are amended or if new claims are added. For search purposes, subgenuses were searched since only subgenuses were elected.
Priority
The present application is a 371 (National Stage) of PCT/US2023/024552 filed June 6, 2023 which claims the benefit of 63/349,623 filed June 7, 2022.
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Withdrawn Rejection
The rejection of claims 14-16 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in view of the amendment received October 7, 2025.
New Rejection Necessitated by Amendment
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 7 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 7 depends on independent claim 1. Independent claim 1 requires a subject with a viral infection wherein the viral infection is VSV, Zika virus, RSV, SARS-CoV-2, vaccinia virus, HSV, Epstein-Barr virus, CMV, or hepatitis B virus. Dependent claim 7 broadens the scope of the Alu-mediated interferon-related pathology to include any viral infection, bacterial infections, microbial infections, fungal infections, yeast infections, etc. Thus, claim 7 fails to further limit the scope of independent claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Maintained and/or Modified* Rejections
*wherein the modification is due to amendment
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, 3, 5, 7, 14, 16, and 18 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. This is a written description rejection.
Independent claim 1 is drawn to a method for preventing an Alu-mediated response in Alu-mediated interferon related pathologies in a subject comprising administering to the subject a therapeutically effective amount of a composition comprising LIN28A, LIN28B, RNA binding sites thereof, or a combination thereof wherein the Alu-mediated interferon related pathologies are viral infections comprising VSV, Zika virus, RSV, SARS-CoV-2, vaccinia virus, HSV, Epstein-Barr virus, CMV, or hepatitis B virus. Independent claim 14 is drawn to a method for preventing an Alu-mediated response to a viral infection caused by upregulation of Alu retrotransposons (RTs) in a subject comprising administering to the subject a therapeutically effective amount of a composition comprising LIN28A, LIN28B, a RNA binding site thereof, or a combination thereof wherein the viral infection is VSV, Zika virus, RSV, SARS-CoV-2, vaccinia virus, HSV, Epstein-Barr virus, CMV, or hepatitis B virus.
The Figures and Examples are silent with regard to a single example of the presently claimed methods. The Figures show LIN28B expression in human placenta, transfected JEG3 cells, and transfected HTR8/SVneo cells. The Figures also show LIN28B increases TNF expression in transfected JEG3 cells but decreases TNF expression in transfected HTR8/SVneo cells. The Figures also show that IFNL3 expression is increased in transfected 293T cells and LIN28B binds Alu. The Figures are silent with regard to any in vitro model or in vivo animal model for any viral infections. Examples 1 and 2 refer to the methods for obtaining the results shown in the Figures. Example 3 is “prophetic” and provides no real information or data. The Figures and Examples are silent with regard to LIN28A or any RNA binding sites. Therefore, one skilled in the relevant art would not reasonably conclude that the Applicants had possession of the invention as claimed since there is not a single example of any in vitro or in vivo animal model of any viral infection utilizing LIN28A, LIN28B, or RNA binding sites thereof.
Please also note that present claim 7 is broader in scope than the viral infections of present independent claim 1 from which claim 7 depends.
See Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See page 1116.).
The skilled artisan cannot envision the method of independent claims 1 or 14. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In Fiddes v. Baird, 30 USPQ2d 1481, 1483, claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class wherein the specification provided only the bovine sequence.
Additionally, Cf. University of Rochester v G.D. Searle & Co., Inc., Monsanto Company, Pharmacia Corporation, and Pfizer Inc., No. 03-1304, 2004 WL 260813 (Fed. Cir., Feb. 13, 2004) held that:
Regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to that subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 112(a) (written description) for claims 1, 3, 5, 7, 14, 16, and 18 were considered but are not persuasive for the following reasons.
Applicants contend that page 2, lines 17-20 refer to how type III IFNs protect against viruses. Applicants contend that LIN28 reduces IFN production by binding to Alu and that viral infection induces Alu RNA.
Applicants’ arguments are not convincing since the present specification lacks written description regarding the presently claimed methods. At least 3 of the 4 cited references at page 2, lines 17-20 only refer to Zika virus (i.e. not the Markush recited in claims 1, 7, or 14). It is also respectfully noted that if applicants wish the examiner of record to consider any references, the references must be provided and an IDS filed. Applicants statements at page 6 of the response received October 7, 2025 broaden what is actually shown in the Figures and Examples.
The Figures show LIN28B expression in human placenta, transfected JEG3 cells, and transfected HTR8/SVneo cells. The Figures also show LIN28B increases TNF expression in transfected JEG3 cells but decreases TNF expression in transfected HTR8/SVneo cells. The Figures also show that IFNL3 expression is increased in transfected 293T cells and LIN28B binds Alu. The Figures are silent with regard to any in vitro model or in vivo animal model for any viral infections. Examples 1 and 2 refer to the methods for obtaining the results shown in the Figures. Example 3 is “prophetic” and provides no real information or data. The Figures and Examples are silent with regard to LIN28A or any RNA binding sites.
Claims 1, 3, 5, 7, 14, 16, and 18 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. This is a scope of enablement rejection.
There are many factors to consider when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any experimentation is “undue”. These factors include, but are not limited to:
1. The breadth of the claims;
2. The nature of the invention;
3. The state of the prior art;
4. The level of skill in the art;
5. The level of predictability in the art;
6. The amount of direction provided by the inventor;
7. The presence or absence of working examples;
8. The quantity of experimentation necessary needed to make or use the invention based on the disclosure.
See In re Wands USPQ 2d 1400 (CAFC 1988):
The breadth of the claims and the nature of the invention:
Independent claim 1 is drawn to a method for preventing an Alu-mediated response in Alu-mediated interferon related pathologies in a subject comprising administering to the subject a therapeutically effective amount of a composition comprising LIN28A, LIN28B, RNA binding sites thereof, or a combination thereof wherein the Alu-mediated interferon related pathologies are viral infections comprising VSV, Zika virus, RSV, SARS-CoV-2, vaccinia virus, HSV, Epstein-Barr virus, CMV, or hepatitis B virus. Independent claim 14 is drawn to a method for preventing an Alu-mediated response to a viral infection caused by upregulation of Alu retrotransposons (RTs) in a subject comprising administering to the subject a therapeutically effective amount of a composition comprising LIN28A, LIN28B, a RNA binding site thereof, or a combination thereof wherein the viral infection is VSV, Zika virus, RSV, SARS-CoV-2, vaccinia virus, HSV, Epstein-Barr virus, CMV, or hepatitis B virus. Accordingly, the claim scope is unduly broad with respect to the encompassed viral infections and the mechanism of action. Please note: present claim 7 broadens the scope of the pathologies recited in present independent claim 1 from which claim 7 depends.
The state of the prior art and the level of predictability in the art:
While there is some correlation between Alu and pathologies including viral infections in the prior art, the prior art is silent with regard to the association of LIN28 to preventing all the presently claimed viral infections. See, for example, Jang et al., 1989, HSV infection induces increased transcription of Alu repeated sequences by RNA polymerase III, FEBS Letters, 258(2): 255-258; Crooke et al., 2021, Reduced A-to-I editing of endogenous Alu RNAs in severe COVID-19 disease, J Immunol, 206(8): 1691-1696; Aune et al., 2022, Alu RNA Structural Features Modulate Immune Cell Activation and A-to-I Editing of Alu RNAs Is Diminished in Human Inflammatory Bowel Disease, Frontiers in Immunology, 13: 818023 (13 pages); Cantarella et al., 2024, Adenovirus small E1A directs activation of Alu transcription at YAP/TEAD- and AP-1-bound enhancers through interactions with the EP400 chromatin remodler, Nucleic Acids Research, 52: 9481-9500; Crooke et al., 2021, Reduced A-to-I editing of endogenous Alu RNAs in lung after SARS-CoV-2 infection, Current Research in Immunology, 2: 52-59; and Li et al., 2021, Alu retrotransposons and COVID-19 susceptibility and morbidity, Human Genomics, 15(2): 11 pages. Lin28 is known to bind Alu (see Elbarbary et al., 2014, Dodging two bullets with one dsRNA-binding protein, Cell Cycle, 13(3): 345-346 and Elbarbary et al., 2013, STAU1 binding 3’ UTR IRAlus complements nuclear retention to protect cells from PKR-mediated translational shutdown, Genes & Development, 27: 1495-1510). However, LIN28 is associated with causing cancer. Therefore, administration of LIN28 must be closely monitored to ensure that cancer is not a side effect of treatment. In addition, in applicant’s own specification, LIN28B had the opposite effect on TNF expression in different cell lines. Thus, it is not clear if LIN28B would have the same effects on different viral infections due, at least in part, to the viral infections occurring in different cell types. In addition, in some viral infections, LIN28 expression is upregulated. Therefore, it would be presumed that the addition of LIN28 would not lead to treatment. See Wu et al., 2015, Lin28B over-expression mediates the repression of let-7 by hepatitis B virus X protein in hepatoma cells, Int J Clin Exp Med, 8(9): 15108-15116; You et al., 2014, Hepatitis B virus X protein upregulates LIN28A/LIN28B through Sp-1/c-Myc to enhance the proliferation of hepatoma cells, Oncogene, 33: 449-460; Han et al., 2020, Association of LIN28B polymorphisms with chronic hepatitis B virus infection, Virology Journal, 17: 81 (9 pages); and McDaniel et al., 2016, Lin28 and let-7: roles and regulation in liver disease, Am J Physiol Gastrointest Liver Physiol, 310: G757-G765. Therefore, the level of predictability in the art is dependent on many factors. While finding treatments for viral infections is important, the state of the art requires vast amounts of data, including in vitro models; in vivo animal models; phase 0-IV clinical trials; etc.
The level of skill in the art:
The level of skill would be high, most likely at the Ph.D. and/or MD level.
The amount of direction provided by the inventor and the existence of working examples:
There are no specific examples directed to the presently claimed invention; nor is there any guidance as to how to specifically utilize LIN28A, LIN28B, or RNA binding sites thereof to treat any viral infection claimed in independent claims 1 and 14 or the broadening claim of dependent claim 7 which is within the scope of the presently claimed invention. The general teachings in the specification regarding LIN28B altering TNF expression, altering IFNL3 expression, and binding to Alu do not provide any guidance with regard to treating viral infections. Furthermore, no direction is provided on how to avoid cancer when administering a known oncogene.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure:
In light of the unpredictability surrounding the claimed subject matter, the undue breadth of the claimed invention’s intended use, and the lack of adequate guidance, one wishing to practice the presently claimed invention would be unable to do so without engaging in undue experimentation. One wishing to practice the presently claimed invention would have to produce additional experiments and data including in vitro models of every pathology and viral infection; in vivo animal models of every pathology and viral infection; and phase 0-IV clinical trials for each pathology and viral infection.
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 112(a) (scope of enablement) for claims 1, 3, 5, 7, 14, 16, and 18 were considered but are not persuasive for the following reasons.
Applicants contend that page 2, lines 17-20 refer to how type III IFNs protect against viruses. Applicants contend that LIN28 reduces IFN production by binding to Alu and that viral infection induces Alu RNA.
Applicants’ arguments are not convincing since the present specification lacks scope of enablement regarding the presently claimed methods. At least 3 of the 4 cited references at page 2, lines 17-20 only refer to Zika virus (i.e. not the Markush recited in claims 1, 7, or 14). It is also respectfully noted that if applicants wish the examiner of record to consider any references, the references must be provided and an IDS filed. Applicants statements at page 6 of the response received October 7, 2025 broaden what is actually shown in the Figures and Examples.
The Figures show LIN28B expression in human placenta, transfected JEG3 cells, and transfected HTR8/SVneo cells. The Figures also show LIN28B increases TNF expression in transfected JEG3 cells but decreases TNF expression in transfected HTR8/SVneo cells. The Figures also show that IFNL3 expression is increased in transfected 293T cells and LIN28B binds Alu. The Figures are silent with regard to any in vitro model or in vivo animal model for any viral infections. Examples 1 and 2 refer to the methods for obtaining the results shown in the Figures. Example 3 is “prophetic” and provides no real information or data. The Figures and Examples are silent with regard to LIN28A or any RNA binding sites.
Claim Rejections - 35 USC § 102
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.
Claims 1, 3, 5, 7, 14, 16, and 18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Burns et al. WO 2020/077295 published April 16, 2020.
For present claims 1, 3, 5, 7, 14, 16, and 18, Burns et al. teach methods of administering LIN28 to subjects to treat viral infections including SARS-CoV-2 wherein administration is intravenous (please refer to the entire specification particularly sections E48, E120, E286; pages 5, 9, 18, 73, 74; claims).
Therefore, the teachings of Burns et al. anticipate the presently claimed method.
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 102 (a)(1) as being anticipated by Burns et al. for claims 1, 3, 5, 7, 14, 16, and 18 were considered but are not persuasive for the following reasons.
Applicants contend that Burns et al. does not teach an Alu-mediated response in Alu-mediated interferon-related pathologies or a viral infection caused by upregulation of Alu RTs. Applicants contend that Burns et al. does not teach administering LIN28B, LIN28A, RNA binding sites thereof, or combinations thereof.
Applicants’ arguments are not convincing since the teachings of Burns et al. anticipate the methods of the instant claims. Burns et al. teach administration of the same product to the same subject population as presently claimed. Therefore, Burns et al. anticipates the presently claimed single step method of administration.
"The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." See In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) and In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968).
A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989). See also Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005) (reference disclosing optional inclusion of a particular component teaches compositions that both do and do not contain that component); Celeritas Technologies Ltd. v. Rockwell International Corp., 150 F.3d 1354, 1361, 47 USPQ2d 1516, 1522-23 (Fed. Cir. 1998) (The court held that the prior art anticipated the claims even though it taught away from the claimed invention. "The fact that a modem with a single carrier data signal is shown to be less than optimal does not vitiate the fact that it is disclosed.").
"Products of identical chemical composition can not have mutually exclusive properties." See In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id. (Applicant argued that the claimed composition was a pressure sensitive adhesive containing a tacky polymer while the product of the reference was hard and abrasion resistant. "The Board correctly found that the virtual identity of monomers and procedures sufficed to support a prima facie case of unpatentability of Spada’s polymer latexes for lack of novelty.").
A discovery of a mechanism of action is not necessarily inventive.
New Rejection Necessitated by Amendment
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.
Claims 1, 3, 5, 7, 14, 16, and 18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Angel et al. WO 2021/222389 published November 4, 2021.
For present claims 1, 3, 5, 7, 14, 16, and 18, Angel et al. teach methods of administering LIN28 to subjects to treat viral infections including SARS-CoV-2 wherein administration is intravenous (please refer to the entire specification particularly pages 4, 5, 22, 23, 25, 32, 39, 41-43, 47, 49; claims).
Therefore, the teachings of Angel et al. anticipate the presently claimed method.
Conclusion
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.
Future Communications
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMBER D STEELE whose telephone number is (571)272-5538. The examiner can normally be reached M-F 8-5.
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/AMBER D STEELE/Primary Examiner, Art Unit 1658