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 .
Election/Restrictions
Applicant’s response to the restriction/ election requirement from 10/6/2025 is acknowledged. Applicant has elected without traverse the invention of Group I, claims 1-14. Applicant has further elected Roxadustat as a species of a low oxygen mimetic compound, and has designated that Roxadustat reads on all of claims 1-14.
The restriction/ election requirement is hereby MADE FINAL. Claims 1-14 are pending, and have been examined herewith to the extent of Applicant’s elected species.
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 1-3, 5, 6, 9, 10, 13 and 14 are rejected under 35 U.S.C. 103 as being obvious over US 20190269553 to Sullivan et al. (“Sullivan”).
As to claims 1-3, 13 and 14, Sullivan discloses a method of reducing the severity or treating an optical disease or disorder associated with reduced meibomian gland (MG) function in a subject by locally administering to an eye tissue of the subject a composition comprising a low oxygen mimetic compound (claims 1, 5; "1. A method of treating meibomian gland dysfunction, the method comprising: reducing oxygen concentration or inducing hypoxia-inducible factors in an eyelid environment of one or more dysfunctional meibomian glands, thereby restoring a hypoxic status of the eyelid environment or stimulating hypoxia-related pathways in one or more dysfunctional meibomian glands....5. A method of claim 1, wherein the hypoxic status is induced pharmaceutically"; abstract, "The methods also include giving local or systemic drugs that lead to the generation of hypoxia-inducible factors in one or more dysfunctional meibomian and sebaceous glands”, para [0011]; "The effects of reduced oxygen concentration can also be elicited by the systemic or local use of agents that induce the generation of HIFs in the dysfunctional MGs. These agents include such drugs as one or more of prolyl hydroxylases inhibitors, (i.e., FG-4592/roxadustat, FG-2216, daprodustat/(GSK1278863, vadadustavAKB-6548, molidustat/BAY 85.3934, desidustav/ZYAN 1").
Sullivan further discloses that MG dysfunction comprises destabilized tear film and increases its osmolarity and evaporation (para [0006]; "MGD, and the resulting meibum insufficiency, destabilize the tear film, and increase its osmolarity and evaporation”). Sullivan further discloses that MG dysfunction comprises destabilized tear film and increases its osmolarity and evaporation (para [0006]; "MGD, and the resulting meibum insufficiency, destabilize the tear film, and increase its osmolarity and evaporation").
Sullivan does not specifically disclose that reduced severity or treatment of said disease or disorder comprise prolonged tear film break up time, improved tear osmolarity, decreased inflammation on the ocular surface, etc. However, administering the same compounds in patients with the same disease/ condition, would have resulted in the same effects. In this regard, it further would have been obvious to have tried and measured prolonged tear film break up time or improved tear osmolarity before and after treatment using methods known in the art, based on the disclosure of Sullivan, making the claim obvious. In this regard, Sullivan further discloses that the local oxygen concentration at the MG in the subject is reduced to no more than 1% (para {0008}; "we have discovered that MGs exist in an environment containing oxygen levels below 1.3%. This low partial pressure of oxygen (pO.sub.2) is “normoxic” or "physioxic" for MGs. For the purposes of this application, we characterize this normoxic/physioxic environment of the MGs as "relatively hypoxic"). Accordingly, it would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to assess the therapeutic effect in terms of decreased pathology parameters.
As to claims 5-6 and 9, Sullivan discloses locally administering (abstract) with low oxygen mimetic compounds such as Roxadustat (i.e., Roxa) (para [0011]), but fails to disclose that the composition is administered at a concentration of 0.01-100 mg/ml, or compound is administered at a concentration of 1-50 ug/ml, or the compound is administered at a dose of 1-300 ug per injection.
However, it would have been prima facie obvious to a person of skill in the art before the effective filing date of the claimed invention to optimize the effective amount and concentration of Roxadustat in the composition, in order to practice Applicant’s claimed invention with a reasonable expectation of success. Motivation to do so is found in Sullivan itself, as it discloses that the in vitro concentration is a result-effective variable. (“[0029] It has been found that roxadustat (20-100 μM), which is a representative of the HIF-inducing agents, activates the hypoxia pathway in IHMGECs by significantly increasing the level of HIF1α. Roxadustat significantly induces lipid production and terminal differentiation of the IHMGECs. [0030] Empirical observations carried out in testing different aspects of the present disclosure indicate that the disclosed treatment strategies to create a hypoxic MG environment or treat with HIF-inducing agents may well serve as new and effective therapies for the treatment of MGD.”). Sullivan further teaches that the therapeutically effective amounts need to be both safe and effective. (“In addition, these approaches could be any safe and effective method to restore a relatively hypoxic environment for the MGs and SGs, and could entail methods to constrict or close blood vessels (in order to restrict the blood flow) in the vicinity of the MGs or SG or inducing HIFs in MGs or SGs.” ([0045])). Accordingly, it would have been obvious to a person of skill in the art before the effective filing date of the claimed invention to optimize the amount of the low oxygen mimetic compound. Generally, mere optimization of ranges will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “When the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimal or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); “The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”
Claims 4, 7 and 8 are rejected under 35 U.S.C. 103 as being obvious over US 20190269553 to Sullivan et al. (“Sullivan”), as applied to claims 1-3, 5, 6, 9, 10, 13 and 14 in the 35 U.S.C. 103 rejection above, and further in view of US 20160256519 to Dana et al. (“Dana”).
Sullivan is discussed in the 35 USC 103 rejection above.
As to claim 4, Sullivan discloses locally administering (abstract) with low oxygen mimetic compounds such as Roxadustat (i-e., Roxa) (para [0011}), but fails to disclose that that the composition in the form of an eye drop.
However, Dana, which pertains to methods of treating dry eye disease in a subject, discloses that the composition is in the form of an eye drop (para [0308]; "Solutions may be manually delivered to the eye in suitable dosage form, e.g., eye drops").
As to claims 7 and 8, Sullivan discloses locally administering (abstract) with low oxygen mimetic compounds such as Roxadustat (i.e., Roxa) (para [0011]), but fails to disclose that the compound is administered to an eye tissue by (subconjunctival) injection. However, Dana discloses that the compound is administered to an eye tissue by injection (para [0313]; "Systemic and focal routes of administration useful in the methods of the invention encompass, without limitation...intravenous injection...periocular and intraocular injection including subconjunctival injection").
Accordingly, it would have been obvious to a person of skill in the art before the effective filing date of the claimed invention to combine the teachings of Sullivan and Dana with a reasonable expectation of success in order to practice Applicant’s claimed invention with local administration accomplished by either an eye drop or by (subconjunctival) injection. The skilled artisan would have been motivated to do so because it would have provided a means of locally treating MGD by established means of administration from the art.
Claims 11 and 12 are rejected under 35 U.S.C. 103 as being obvious over US 20190269553 to Sullivan et al. (“Sullivan”), as applied to claims 1-3, 5, 6, 9, 10, 13 and 14 in the 35 U.S.C. 103 rejection above, and further in view of US 20130197016 A1 to Brigell et al. (“Brigell") and Provenzano et al., Oral Hypoxia–Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat (FG-4592) for the Treatment of Anemia in Patients with CKD, Clinical Journal of the American Society of Nephrology 11(6):p 982-991, June 2016 (“Provenzano”).
As to claim 11, Sullivan discloses locally administering (abstract) with low oxygen mimetic compounds such as Roxadustat (i.e., Roxa) (para [0011]).
Sullivan does not disclose compound is administered orally at a dose of 50-70 mg per oral administration, and that the oral dose does not exceed 3.0 mg/kg of body weight, per Applicant’s claims 11 and 12, respectively.
However, Brigell, which pertains to dosing regimens for ocular vascular disease, discloses that a disclosed compound is administered at a dose of 50-70 mg per oral administration (para [0106]; "Compound 2 or vehicle was orally dosed ... to Brown Norway rats at doses ranging from of 3 to 30 mg/kg were given daily for 14 days [i.e., about 60 mg per 2 kg rat). Brigell further discloses that the oral dose does not exceed 3.0 mg/kg of body weight (para [0014]; rats administered a single oral dose of 0.3 mg/kg” para [0106]).
Roxadust itself is a drug known in the art for oral administration.
Provenzano discloses as a way of background that Roxadustat (FG-4592) is an oral hypoxia–inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis, regulates iron metabolism, and reduces hepcidin. (Abstract).
Accordingly, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine to combine the teachings of Sullivan, Brigell and Provenzano with a reasonable expectation of success by administering with low oxygen mimetic compounds such as Roxadustat, as disclosed by Sullivan. The skilled artisan would have been further motivated to arrive at the therapeutically effective amount of the compound motivated by the desire to achieve therapeutic efficacy and safety, and guided by the disclosure in the art of therapeutic doses for the drug itself and for other compounds in the treatment of eye diseases specifically. “When the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimal or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); “The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SVETLANA M IVANOVA whose telephone number is (571)270-3277. The examiner can normally be reached 8:30-5:00.
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, 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.
/SVETLANA M IVANOVA/ Primary Examiner, Art Unit 1627