DETAILED ACTION
Notice of AIA Status
The instant application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the Leahy-Smith America Invents Act (AIA ).
If the status of the application as subject to AIA or pre-AIA is incorrect, any correction of the statutory basis (e.g., changing from AIA to pre-AIA ) for a rejection under 35 U.S.C. §§ 102 and/or 103 will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Status of the Claims
The listing of claims filed 6 May 2026 has been examined.
Claims 1–6, 11–17, 25, 26, 33, 36, 41, 50, 54, 60, 61, 67, and 68 are pending. Claims 1–6, 12–15, 25, 33, 36, 41, 50, 54, 60, 67, and 68 are amended. Claims 7–10, 18–24, 27–32, 34, 35, 37–40, 42–49, 51–53, 55–59, and 62–66 are canceled.
Benefit of Earlier Filing Date
The instant application was filed 5 June 2024; is a national stage application of PCT/US2022/029887, filed 18 May 2022; and claims the benefit of an earlier filing date of U.S. Prov. Pat. App. No. 63/286,989, filed 7 December 2021. Applicant’s claim is acknowledged.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 11 July 2024 and 6 May 2026 are acknowledged and have been considered.
Objections to the Specification
The abstract of the disclosure is objected to because it recites phrases that can be implied (“The present invention is directed to”).
For guidelines for the preparation of patent abstracts, see MPEP § 608.01(b) (Explaining: The abstract should be in narrative form and avoid legal phraseology (e.g., means, said), terms referring to purported merits of the invention (e.g., new, novel), and phrases that can be implied (e.g., The disclosure concerns, The disclosure defined by this invention). The language should be clear and concise, and not repeat information given in the title. It should not compare the invention with the prior art. The abstract is generally limited to a single paragraph within the range of 50 to 150 words in length.).
Appropriate correction is required.
Examiner recommends: “M[[m]]ethods of . . .”
Claim Rejections - 35 U.S.C. § 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. § 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Graham v. John Deere Co., 383 U.S. 1, 17 (1966); MPEP § 2141(II).
(i) Claims 1–6, 11–17, 25, 26, 33, 36, 41, 50, 54, 60, 67, and 68 are rejected under 35 U.S.C. § 103 as being unpatentable over US 7,816,344 (“Baker”) [IDS] in view of Ethambutol, drugs.com, Archived 21 January 2021 (“Drugs.com”) and admissions in the instant specification (“Spec.).
The Graham factors are addressed in turn below.
Determining the scope and contents of the prior art
Applicant acknowledges: “There is a need for improved methods of treating non-tuberculosis Mycobacteria (NTM) infections in human subjects.” (Clean Sub. Spec., ¶2).
Baker discloses there is a need to discover broad spectrum antimicrobials because the global rise of microorganisms resistant to antibiotics and antimicrobials poses a major threat. (Baker: 1:14–22) (col:lines).
Baker discloses boron-containing compounds are useful antimicrobials. (Id., 1:23–41).
Baker discloses a combination comprising epetraborole. (Id, 278:29–41).
Baker discloses the combination can be with ethambutol. (Id., 58:47–53).
Baker discloses killing or inhibiting the growth of microorganisms Mycobacterium avium-intracellulare and Mycobacterium catarrhalis—both of which are non-tuberculosis Mycobacterium. (Id., 86:3; 87:23–24).
Baker discloses the microorganism is inside of a human. (Id., 85:44–50; 99:66–67).
Baker discloses treating a disease caused by the microorganisms. (Id., 89:34–91:51).
Baker discloses oral dose formulations. (Id., 105:53–108:24).
Baker states the appropriate dosage can be determined: “Appropriate doses will be readily appreciated by those skilled in the art. It will be appreciated that the amount of a compound of the invention required for use in treatment will vary with the nature of the condition being treated and the age and the condition of the patient and will be ultimately at the discretion of the attendant physician or veterinarian.” (Id., 56–63).
Baker discloses dosage levels of about 5 mg to about 250 mg per kilogram of body weight per day. (Id., 109:60–110:2).
Baker discloses unit dosage forms containing about 1 mg to about 500 mg of the active ingredient. (Id.).
Baker discloses administering the compounds in a therapeutically effective amount. (Id., 126:13–51).
Baker discloses the dosage amount and intervals can be adjusted to provide a desired plasma level. (Id., 126:36–43).
Baker discloses a combination with rifampin, azithromycin, clarithromycin, or amikacin. (Id., 57:53–58:53).
Baker discloses the components of a combination can be administered simultaneously or sequentially, and in single or multiple unit dosage forms. (Id., 59:4–19).
Baker states: “Appropriate doses of known therapeutic agents will be readily appreciated by those skilled in the art.” (Id.).
Baker does not limit the disclosures to a particular patient population, such as a human having had or not having had a prior NTM treatment.
Drugs.com discloses ethambutol is used in conjunction with an antimycobacterial agent to treat non-tuberculosis Mycobacteria (NTM) infections in human subjects, including Mycobacterium avium Complex. (Drugs.com, pp.1–3).
Drugs.com discloses first-line treatment with ethambutol or patients with treatment failure. (Id., p.1).
Drugs.com discloses oral administration of ethambutol at a dosage of 15–25 mg/kg and up to 1 gram per day. (Id., pp.3–7).
Drugs.com discloses ethambutol hydrochloride is commercially available in tablet form at 100 mg or 400 mg. (Id., p.13).
Drugs.com discloses oral administration of ethambutol with rifampin, clarithromycin, or azithromycin. (Id., p.5).
Drugs.com does not limit the disclosures to a particular patient population, such as a human having had or not having had a prior NTM treatment.
Ascertaining the differences between the prior art and the claims at issue
Baker does not disclose a single embodiment of the claimed method.
Resolving the level of ordinary skill in the pertinent art
The level of one of ordinary skill may be found by inquiring into: (i) the type of problems encountered in the art; (ii) prior art solutions to those problems; (iii) the rapidity with which innovations are made; (iv) the sophistication of the technology; and (v) the education level of active workers in the field. Custom Accessories, Inc. v. Jeffrey-Allan Industries, Inc., 807 F.2d 855, 962 (Fed. Cir. 1986). All of the factors may not be present in every case, and one or more of them may predominate. Envtl. Designs, Ltd. v. Union Oil Co., 713 F.2d 693, 696 (Fed. Cir. 1983). Based on the typically high education level of workers in the pharmaceutical art and the high degree of sophistication required to solve problems encountered in the art, Examiner finds a person having ordinary skill in the art would have at least a college degree in chemistry, biology, biochemistry, pharmacology, or a related field, and several years of experience.
Considering objective evidence present in the application indicating obviousness or nonobviousness
The instant application states the combination of epetraborole and ethambutol result in a synergistic activity against M. avium and M. interacellulare, but not against the other microorganisms screened, as shown in the Table below. (Clean Sub. Spec., ¶453).
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The question of obviousness
Based on the above factors, it would have been prima facie obvious for a person having ordinary skill in the art prior to the filing of the instant application to arrive at the claimed method based on the disclosures in Baker and Drugs.com because the cited references disclose the claimed features. Although Baker discloses numerous compounds, epetraborole is the only compound in the claims, which indicates its importance and a basis for selecting it. Furthermore, epetraborole is claimed as a combination. Baker discloses numerous therapeutics that can be included as a component in the combination with epetraborole, including ethambutol. Baker highlights ethambutol as an “exemplary embodiment” in a short list with 16 other therapeutic agents. And Drugs.com discloses ethambutol is used in conjunction with an antimycobacterial agent to treat non-tuberculosis Mycobacteria (NTM) infections in human subjects, including Mycobacterium avium Complex. Thus, one of ordinary skill in the art would have been motivated to combine epetraborole and ethambutol based on the disclosures in Baker and Drugs.com for the purpose of treating NTM infections. There would have been a reasonable expectation of success because Baker and Drugs.com disclose the features of the claimed method and provide guidance with respect to carrying out the claimed method.
The claimed dosage amounts, dosage regimen, or patient population appear to be disclosed in Baker and Drugs.com, either specifically or as encompassed by a disclosed range. To the extent there are any differences between those claim features and the disclosures in Baker and Drugs.com, there is no evidence in the specification suggesting a claimed dosage amount, dosage regimen, or patient population has a nexus to an unexpected result or is otherwise critical to the claimed method of achieving a positive therapeutic response against an NTM infection.
The evidence regarding antibacterial synergy testing in the instant specification has been considered. That evidence shows that only one combination (epetraborole and ethambutol) exhibited synergistic activity, and that combination only exhibited the synergistic activity against two microorganisms out of the seven disclosed in the table. Accordingly, the evidence of unexpected results is not commensurate in scope with any of the rejected claims.
(ii) Claims 50 and 54 are rejected under 35 U.S.C. § 103 as being unpatentable over Baker in view of Drugs.com and Spec. as applied to claims 1 and 13 above, and further in view of Sharma et al., Indian J. Med. Res. (2020), 152, 185–226 (“Sharma”).
Baker and Drugs.com do not disclose the use of a sputum sample for monitoring the quantitative colony count and determining the positive therapeutic response.
Sharma discloses collecting and processing sputum samples from patients with NTM infections. (Sharma, passim, e.g., pp.198, 202).
There is no evidence in the specification suggesting the use of a sputum sample to monitor the quantitative colony count and to determine the positive therapeutic response has a nexus to an unexpected result or is otherwise critical to the claimed method of achieving a positive therapeutic response against an NTM infection.
Based on the above factors, it would have been prima facie obvious for a person having ordinary skill in the art prior to the filing of the instant application to arrive at the claimed method based on the disclosures in Baker, Drugs.com, and Sharma because the cited references disclose the claimed features and establish that collecting and processing sputum samples from patients with NTM infections is known and/or routine in the art.
Conclusion
Claim 61 is allowed.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jason Nolan at (571) 272-2480. The examiner can normally be reached Monday through Friday between 9:00–5:00.
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/JASON M. NOLAN/Patent Examiner, Art Unit 1623
/GEORGE W KOSTURKO/Primary Examiner, Art Unit 1621
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