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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on July 10th, 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
The listing of references in the specification (starting on page 65) is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The use of the terms CELLTITER-GLOTM, KOLLIPHORTM, etc. which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. The following title is suggested: “Use of tilorone against Marburg Virus Infection.”
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
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 Interpretation
Claim 1 mentions a method of prevention of a disease caused by a Marburg virus (MARV) comprising administration of tilorone. The specification defines “prevent” as to stop something from happening, or taking advance measures against something possible or probably. Thus, the term is being interpreted as prophylactic administration to subjects at risk of contracting a MARV infection.
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); in view of Baker et al. (Acta Cryst. 2016, D72, 49-58 – cited in IDS).
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 et al. 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); in view of Baker et al. (Acta Cryst. 2016, D72, 49-58 – cited in IDS); 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 et al. are disclosed above and incorporated herein.
While Ekins and Baker et al. do not teach Musoke and Angola variants of MARV, the teachings of Cross et al. 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.
Conclusion
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.
Examiner interviews are available via telephone 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, Kortney L. Klinkel can be reached at (571) 270-5239. 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.
/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/SAN MING R HUI/Primary Examiner, Art Unit 1627