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 Claims
Claims 1-8, 10, 12, 14, 20, 22-28, 35, 37, and 41 are pending in the instant application.
Claims 9, 11, 13, 15-19, 21, 29-34, 36, and 38-40 have been canceled.
Domestic Benefit
Acknowledgement is made of Applicant’s claim for domestic benefit on the basis of the provisional applications 63/286,989 and 63/416,059, filed December 7th, 2021 and October 14th, 2022, respectively. The instant Claims are fully supported by U.S. Provisional Application No. 63/286,989, and will be evaluated with an effective filing date of December 7th, 2021.
Information Disclosure Statement
The Information Disclosure Statements filed on July 11th, 2024 and December 17th, 2024 have been fully considered by the examiner, except where marked with a strikethrough.
Specification
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.
Applicant is reminded of the proper content of an abstract of the disclosure.
In chemical patent abstracts for compounds or compositions, the general nature of the compound or composition should be given as well as its use, e.g., “The compounds are of the class of alkyl benzene sulfonyl ureas, useful as oral anti-diabetics.” Exemplification of a species could be illustrative of members of the class. For processes, the type of reaction, reagents and process conditions should be stated, generally illustrated by a single example unless variations are necessary.
The abstract of the disclosure is objected to because it is fewer than 50 words in length. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The 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 of the errors of which Applicant may become aware of in the specification.
Claim Objections
Claim 41 is objected to because of the following informalities:
Claim 41 should read “… wherein the non-tuberculosis Mycobacterium is selected from …”. Presently, “Mycobacterium” is not written in the claim.
Appropriate correction is required.
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 1-8, 10, 12, 14, 20, 22-28, 35, 37, and 41 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 treating a non-tuberculosis Mycobacteria infection, does not reasonably provide enablement for treating any non-tuberculosis Mycobacteria-associated disease. 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.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (1) The breadth of the claims, (2) The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Nature of the invention:
The invention is drawn to a method of treatment of a non-tuberculosis Mycobacteria infection or a non-tuberculosis Mycobacteria-associated disease.
Breadth of the invention:
The scope of the claimed invention is very broad. With respect to Mycobacteria-associated diseases, this is inclusive of an array of known diseases as well as diseases that have either yet to be discovered, or diseases that are presently known, but later are discovered to be Mycobacteria-associated. Can the Applicant simply “reach through” and obtain patent protection for a method of treating a disease that is either not known presently, or later is classified as Mycobacteria-associated?
State of the prior art and predictability in the art:
With respect to treating Mycobacteria-associated diseases, Sharma et. al. (“Epidemiology, diagnosis & treatment of non-tuberculous mycobacterial diseases”, Indian J Med Res, 2020; hereinafter referred to as Sharma) represents the state of the prior art.
At the Abstract, Sharma teaches treatment response of non-tuberculous mycobacterial pulmonary diseases is variable.
At Page 219, Sharma states, “Less toxic and more effective drug treatment regimens administered for short periods should be developed for the treatment of NTM-PD especially due ot M. abscessus as these NTM species respond poorly to treatment with frequent relapses occurring after stopping treatment.”
Taken together, this demonstrates the lack of predictability in treating Mycobacterial-associated diseases.
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F. 2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F. 2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F. 2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
Level of ordinary skill in the art:
An ordinary artisan in the area of drug development would have experience in synthesizing chemical compounds for particular activities. The synthesis of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against a particular biological target (i.e., receptor, enzyme, etc.) is well known. Additionally, while high throughput screening assays can be employed, developing a therapeutic method, as claimed, prior to synthesizing and testing compounds is generally not well-known or routine, given the complexity of certain biological systems.
The amount of direction provided and working examples:
Beginning at Page 16 of the instant specification, several examples of the instant invention are disclosed.
Beginning at Page 16, Example 1 is drawn to the determination of minimum inhibitory concentrations of a variety of compounds against a variety of species of Mycobacteria.
Beginning at Page 17, Example 2 is drawn to the determination of the activity of epetraborole hydrochloride in several pairwise combinations against various species of Mycobacteria to determine whether the combinations demonstrated an indifferent, additive, or synergistic effect, as disclosed beginning at Page 19 of the instant specification.
Example 3 is drawn to the determination of spontaneous resistance frequency.
Taken together, these examples demonstrate the efficacy of the instant invention in inhibiting the growth of various Mycobacteria. No examples have been provided demonstrating the efficacy of the instant invention in treating Mycobacteria-associated diseases. Given the aforementioned breadth of the instantly claimed invention and lack of predictability in treating Mycobacteria-associated diseases, the instant disclosure is enabling for the treatment of non-tuberculosis Mycobacteria infections, but not for the treatment of any non-tuberculosis Mycobacteria-associated disease.
MPEP § 2164.01 (a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F. 2d 1557, 1556, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).”
Genentech Inc. v Novo Nordisk A/S (CAFC) 42 USPQ 2d 1001 states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “patent protection is granted in return for enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”.
Therefore, in view of the Wands factors and In re Fisher (CCPA 1970) discussed above, to practice the claimed invention herein, a person having ordinary skill in the art would have to engage in undue experimentation to determine the practicability of treatment of any Mycobacteria-associated disease, with no assurance of success.
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.
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.
Claims 1-5, 8, 10, 12, 14, 20, 22-28, 35, 37, and 41 are rejected under 35 U.S.C. 103 as being unpatentable over Eagle et. al. (US 2019/0216834 A1; cited on Applicant’s Information Disclosure Statement filed July 11th, 2024; hereinafter referred to as Eagle) in view of Ganapathy et. al. (“Epetraborole Is Active against Mycobacterium abscessus”, Antimicrob Agents Chemother., September 2021; cited on Applicant’s Information Disclosure Statement filed July 11th, 2024; hereinafter referred to as Ganapathy).
Regarding Claim 1, Eagle teaches at Page 17, Claim 2, a method of treating a nontuberculosis mycobacteriumlung (NTM) infection comprising administering a macrolide antibiotic and ethambutol. Also, at Page 13, Paragraph 0128, Eagle teaches “In another embodiment, the liposomal aminoglycoside composition provided herein is administered to a patient in need of treatment of an NTM lung disease with one or more additional therapeutic agents, and the one or more additional therapeutic agents is ethambutol …”
Regarding Claims 2-3, at Page 18, Claims 96-98, Eagle teaches further administering as part of the aforementioned method a rifamycin compound where the rifamycin compound is rifampin or rifabutin. Additionally, at Page 12, Paragraph 0125, Eagle teaches treatment of NTM lung disease including administration of a rifamycin compound that is rifampin, rifabutin, rifapentine, rifaximin, or a mixture thereof.
Regarding Claims 4-5, Eagle teaches at Claim 2 as part of the aforementioned method of treating a NTM lung infection administration of a macrolide antibiotic in addition to ethambutol. At Page 18, Claim 95, Eagle teaches the macrolide antibiotic can be azithromycin or clarithromycin. This is also taught by Eagle at Page 12, Paragraphs 0123-0124.
Regarding Claim 8, Eagle teaches at Page 12, Paragraph 0048, Eagle teaches the NMT infection can be due to M. chelonae. The instant specification acknowledges at Page 14, Paragraph 0058, that M. chelonae is rapidly growing.
Regarding Claims 12, 14, 35 and 41 at Page 18, Claim 32, Eagle teaches the NTM infection treated by the aforementioned method is a M. avium lung infection. Further, at Page 12, Paragraph 0048, Eagle teaches the NTM infection can be due to M. chelonae.
Regarding Claim 20, Eagle teaches at Page 1, Paragraph 0007, that the patient in need of treatment has cystic fibrosis, bronchiectasis, or suffers from a chronic obstructive pulmonary disorder.
Regarding Claim 22, at Page 12, Paragraph 0115, Eagle teaches the patient treated can have pulmonary fibrosis.
Regarding Claim 24, as previously mentioned, Eagle teaches the method of Claim 2 is directed to the treatment of a lung infection.
Regarding Claim 28, Eagle teaches at Page 18, Claims 110-111 that the patient in need of treatment is refractory.
Eagle does not teach administration of epetraborole in combination with ethambutol.
At the abstract, Ganapathy states “Here, we find that the nonhalogenated benzocaborole epetraborole, a clinical candidate developed for Gram-negative infections is also active against M. abscessus in vitro and in a mouse model of infection. This expands the repertoire of advanced lead compounds for the discovery of a benzoxaborole-based candidate to treat M. abscessus lung disease.”
Therefore, at the time of filing, it was known in the art that both ethambutol and epetraborole were effective in treating an NMT infection. Per MPEP 2144.06, I., “"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072”.
Regarding Claims 10, 23, 25-27, and 37, applying KSR exemplary rationale E, a person having ordinary skill in the art would have found it prima facie obvious to try the method taught by Eagle in view of Ganapathy to address the limitations instantly recited. Regarding Claim 10, Eagle broadly teaches treatment of non-tuberculosis Mycobacteria. Therefore, a person having ordinary skill in the art would reasonably ascertain that it is obvious to try treatment of slowly growing Mycobacteria. Regarding Claims 23, 25-27, and 37, there is nothing to suggest in the method made obvious by Eagle in view of Ganapathy that a patient previously suffering from tuberculosis, infection in two or more organs in the body, infection in the lymph nodes, treatment-naïve infection, or having nodular bronchiecstasis would preclude them from treatment in the instant method.
Claims 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Eagle in view of Ganapathy in further view of Liu et. al. (Water-Insoluble Drug Formulation, CRC Press, 2008, Chapter 15, Pages 417-435; hereinafter referred to as Liu).
As noted above, Eagle in view of Ganapathy obviates the method as recited at instant Claim 1.
Eagle in view of Ganapathy does not obviate the administration of epetraborole as a pharmaceutically acceptable salt.
At Page 417, Liu teaches low aqueous solubility of a drug as a common problem in formulation development and in the in vivo performance of the dosage form of drugs. Further, Liu teaches modifying solubility of organic compounds could require extreme alterations of pH that are outside physiological acceptable limits, or at which stability problems arise. Liu teaches modifying a drug to be administered in a salt formulation addresses these concerns.
Applying KSR exemplary rationale C, it would have been prima facie obvious to a person having ordinary skill in the art to attempt the administration of a pharmaceutically acceptable salt of epetraborole to avoid the problems associated with low aqueous solubility of a drug with reasonable expectation of success.
Conclusion
Claims 1-8, 10, 12, 14, 20, 22-28, 35, 37, and 41 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANIEL JOHN BURKETT whose telephone number is (703)756-5390. The examiner can normally be reached Monday - Friday.
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, Jeffrey Murray can be reached at (571) 272-9023. 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.
/D.J.B./Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624
Prosecution Insights