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, 9-11, and 20-21 are pending in this application. Claims 2-8 and 12-19 have been cancelled by applicant.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1 and 9-11 are rejected under 35 U.S.C. 103 as being unpatentable over Ekins et al. (Antimicrobial Agents and Chemotherapy, 62, 2, e01711-17, 13 pages – cited in IDS – previously cited) (“Ekins”); in view of Baker et al. (Acta Cryst. 2016, D72, 49-58 – cited in IDS – previously cited) (“Baker”).
Regarding claim 1, Ekins discloses that mice infected with Ebola virus (EBOV) treated with tilorone showed 90% survival, and discloses that tilorone doses given 2 to 24 h post-infection and continued for 7 days was fully protective against EBOV-disease (EVD) (abstract, last 5 lines). Ekins teaches EBOV and Marburg virus (MARV) are both members of the filovirus family, and teaches that members of this group work similarly in that they form viral particles and encode their genome in the form of single-stranded neg-sense RNA. Ekins teaches that both viruses cause severe disease in humans in the form of hemorrhagic fevers.
While Ekins does not specifically teach tilorone for the treatment of MARV infections, the teachings of Baker are relied upon for these disclosures.
Baker also teaches that EBOV and MARV are in the Filoviridae family and both cause severe hemorrhagic fever in humans. Both viruses were first reported in Africa and are closely related in structure, with both being membrane enveloped viruses which contain negative sense, single stranded RNA (ssRNA), encoding seven genes that generate more than seven proteins (abstract; and page 50, col 1, para. 2). Baker discloses the fatality rate of a MARV infection in a previous outbreak was 90%, same as that of EBOV in the past, accentuating the need for treatment (page 50, col. 1, end of para. 1).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to try treatment of a MARV infection in a subject by administering tilorone, as taught by Ekins in view of Baker. One of ordinary skill would have been motivated to do so in view of Ekins’ and Baker’s disclosure that EBOV and MARV belong to the same family of viruses; and Baker’s teachings of the high mortality rate associated with MARV infections. One of ordinary skill would have had a reasonable expectation of success in view of Ekins’ disclosure that tilorone is effective in treating EBOV infections; and Baker’s additional teachings of the structural similarities of EBOV and MARV, with both being enveloped viruses which contain negative sense, single stranded RNA (ssRNA), showing similar mechanisms of action.
Regarding claims 9-10, Ekins discloses tilorone has excellent plasma stability in humans (abstract, lines 9-10) and EBOV and MARV viruses cause severe disease in humans and non-human primates (page 1, 7th to last line).
Regarding claim 11, Ekins teaches tilorone as an orally bioavailable drug (reading on oral administration) (abstract, line 1). While Ekins doesn’t specifically disclose oral administration, instead uses intraperitoneal administration to mice, it would have been prima facie obvious to one of ordinary skill to administer treatment orally. One of ordinary skill would have been motivated to do so in order to avoid painful injections required for intraperitoneal administration. One of ordinary skill would have had a reasonable expectation of success in view of Ekins’s disclosure that tilorone is orally bioavailable.
Claims 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Ekins et al. (Antimicrobial Agents and Chemotherapy, 62, 2, e01711-17, 13 pages – cited in IDS – previously cited) (“Ekins”); in view of Baker et al. (Acta Cryst. 2016, D72, 49-58 – cited in IDS – previously cited) (“Baker”); as applied to claims 1 and 9-11; further in view of Cross et al. (Journal of Infectious Diseases, 2015, 212:S258-270).
The teachings of Ekins and Baker are disclosed above and incorporated herein.
While Ekins and Baker do not teach Musoke and Angola variants of MARV, the teachings of Cross are relied upon for these disclosures.
Cross teaches phylogenetic comparisons of known Marburg virus (MARV) strains reveal 2 distinct genetic lineages: Ravn and the Lake Victoria Marburg complex (e.g. Musoke, Popp, and Angola strains) (abstract), with the Musoke and Angola strains falling under the same branch.
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer treatment of an Angola or Musoke infection of MARV, as taught by Ekins and Baker in view of Cross. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Ekins’ teachings that tilorone is an effective treatment for EBOV; Baker’s disclosure of the structural similarities between EBOV and MARV; and Cross’ teaching of different strains of the related strains of MARV, including Musoke and Angola.
Response to Arguments
Specification/ Drawings
Applicant’s arguments, see pages 4-6, filed 03/23/2026, with respect to the objections to the specification and drawings have been fully considered and are persuasive. The objections to the specification and drawings have been withdrawn.
Claim Rejections - 35 USC § 103
Applicant's arguments filed 03/23/2026 have been fully considered but they are not persuasive.
As an initial matter, Applicant is advised that MPEP 716.01(c) makes clear that “[t]he arguments of counsel cannot take the place of evidence in the record” (In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965)).
Applicant cites MPEP 2143.01 to argue that the mere fact that references can be combined does not render combination obvious unless the results would have been predictable to one of ordinary skill in the art. Applicant argues the Office has applied hindsight reasoning in advancing the rejections of record. Applicant states that “the proposed motivations provided by the Office… are at best recognition of unsolved problems” and states their method is novel and inventive advance of the cited art of record. Applicant reinstates that Ekins and Baker at best note the problem of Marburg viruses; and that Cross at best discloses attempts to make phylogenetic comparisons of known Marburg virus strains. Applicant states, when considered as a whole, Baker teaches away from the subject matter of the present claims, and that there is no motivation to combine.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Applicant's arguments do not comply with 37 CFR 1.111(c) because they do not clearly point out the patentable novelty which he or she thinks the claims present in view of the state of the art disclosed by the references cited or the objections made. Further, they do not show how the amendments avoid such references or objections.
Applicant's arguments fail to comply with 37 CFR 1.111(b) because they amount to a general allegation that the claims define a patentable invention without specifically pointing out how the language of the claims patentably distinguishes them from the references.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In this case, Ekins clearly discloses that mice infected with Ebola virus (EBOV) treated with tilorone showed 90% survival, and discloses that tilorone doses given 2 to 24 h post-infection and continued for 7 days was fully protective against EBOV-disease (EVD) (abstract, last 5 lines). Ekins teaches EBOV and Marburg virus (MARV) are both members of the filovirus family, and teaches that members of this group work similarly in that they form viral particles and encode their genome in the form of single-stranded neg-sense RNA. Ekins teaches that both viruses cause severe disease in humans in the form of hemorrhagic fevers.
Baker also teaches that EBOV and MARV are in the Filoviridae family and both cause severe hemorrhagic fever in humans. Both viruses were first reported in Africa and are closely related in structure, with both being membrane enveloped viruses which contain negative sense, single stranded RNA (ssRNA), encoding seven genes that generate more than seven proteins (abstract; and page 50, col 1, para. 2). Baker discloses the fatality rate of a MARV infection in a previous outbreak was 90%, same as that of EBOV in the past, accentuating the need for treatment (page 50, col. 1, end of para. 1).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to try treatment of a MARV infection in a subject by administering tilorone, as taught by Ekins in view of Baker. One of ordinary skill would have been motivated to do so in view of Ekins’ and Baker’s disclosure that EBOV and MARV belong to the same family of viruses; and Baker’s teachings of the high mortality rate associated with MARV infections. One of ordinary skill would have had a reasonable expectation of success in view of Ekins’ disclosure that tilorone is effective in treating EBOV infections; and Baker’s additional teachings of the structural similarities of EBOV and MARV, with both being enveloped viruses which contain negative sense, single stranded RNA (ssRNA), showing similar mechanisms of action.
In response to Applicant’s argument that Baker teaches away from the subject matter of the present claims; Applicant is advised that, per MPEP 2123 (I): 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.").
In order for Applicant to overcome the obviousness rejections of record, Applicant would need to demonstrate, for example, that other known Ebola (EBOV) treatments have not been effective in treating infections of the closely related MARV, thus proving the surprising and unexpected ability of the instantly claimed methods comprising administration of tilorone (known to be effective for EBOV) for the treatment of MARV.
It is noted that the response above should not be construed as an invitation to file an after final declaration. See MPEP 715.09.
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 JACKSON J HERNANDEZ whose telephone number is (571)272-5382. The examiner can normally be reached Mon - Thurs 7:30 to 5.
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/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627
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