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 . In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection 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.
Claim Rejections - 35 USC § 112 –
Indefiniteness, Lack of Antecedent
Basis and Broad to Narrow Limitations
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 31-32, 38, 41-42 and 46-61 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, claim 31 recites the broad recitation “amphotericin B”, and the claim also recites “(AmB)” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
The Applicant is encouraged to remove the parenthesis from the claim.
Regarding lack of antecedent basis, claim 55 recites the limitation "the CFTR anion channel" in line two. There is insufficient antecedent basis for this limitation in the claim.
The Applicant is encouraged to correct for antecedent basis.
Claim Rejections - 35 USC § 103 - Obviousness
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.
Claim(s) 31-32, 38, 42, 46-54 and 61 are rejected under 35 U.S.C. 103 as being unpatentable over Boni et al (USP 7,544,369 B2).
Boni taught [abstract] a method of treating cystic fibrosis (CF) patients comprising the pulmonary administration, of an effective amount [col 3, lines 53-67], of a liposomal/complexed anti-infective, to the patient. The anti-infective was amphotericin B (AmB) [col 2, line 46], and the lipid component of the liposome was cholesterol [claims 1 and 5].
An effective amount was recognized as an amount effective to treat, reduce, ameliorate, eliminate or prevent one or more symptoms of the disease sought to be treated, or the condition sought to be avoided or treated, or to otherwise produce a clinically recognizable change in the pathology of the disease or condition. Amelioration included reducing the incidence or severity of infections in animals treated prophylactically. In certain embodiments, the effective amount was one effective to treat or ameliorate, after symptoms of lung infection arose. In certain other embodiments, the effective amount was one effective to treat or ameliorate the average incidence or severity of infections in animals treated prophylactically (as measured by statistical studies) [col 3, lines 53-67].
Claim 31 is rendered prima facie obvious over the teachings of Boni, because it is prima facie obvious to combine prior art elements according to known methods, in order to yield predictable results. In the instant case, all the claimed elements (e.g., administration, to cystic fibrosis patients, of amphotericin B and sterol) were known in the prior art (e.g., Boni), and one skilled in the art could have combined the elements as claimed by known methods, with no change in their respective functions, and the combination would yield nothing more than predictable results (e.g., a treatment of cystic fibrosis patients) to one of ordinary skill in the art. MPEP 2143.A.
The instant claim 31 recites increasing the pH or decreasing the viscosity (of airway surface liquid), thereby increasing the pH of airway surface liquid in cystic fibrosis patients, by administering therapeutically effective amounts of amphotericin B and a sterol.
The instant claim 61 recites the pH remains increased (following administration of the AmB and the sterol), further limited by an amount of time (at least 2 hours, up to and including, at least 48 hours).
Boni taught treating CF patients, comprising the administration of an effective amount of AmB and cholesterol.
It appears that the methods (therapeutic administration to CF patients) and formulations (AmB and sterol) of the instant claims, and those of the prior art (effective administration of AmB and cholesterol to CF patients), would reasonably be expected to have substantially the same physical and chemical properties (increasing the pH or decreasing the viscosity of airway surface liquid, wherein the pH remains increased after administration, thereby increasing the pH of airway surface liquid in the patient).
Inherent features need not be recognized at the time of the invention. There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. MPEP 2112 II. It should be noted that a chemical composition (or formulation), and its properties, are inseparable. If the prior art teaches the identical chemical compounds, then the properties that the Applicant discloses and/or claims are necessarily present.
Boni reads on claims 31-32, 38, 42, 47-50 and 61.
Claims 46 and 48 are rendered prima facie obvious because Boni taught that [col 7, lines 42-55] the resulting liposomes/complexes separated into homogeneous populations, using methods well known in the art (e.g., separate pharmaceutical compositions could be administered).
Regarding claims 47 and 49-50, Boni taught a complexed formulation, as previously discussed.
Claims 51-52 are rendered prima facie obvious because Boni taught intrathecal administration [col 4, lines 3].
Claims 53 and 54 are rendered prima facie obvious because Boni taught administration, for inhalation, by aerosol [col 4, lines 1-5].
Claim 60 is rendered prima facie obvious because Boni taught antibiotics [col 2, line 6; col 3, line 13]. Effective amounts were previously discussed (see Boni).
Claim(s) 41 is rejected under 35 U.S.C. 103 as being unpatentable over Boni et al (USP 7,544,369 B2), in view of Adler-Moore et al (Medical Mycology, 2016, 54(3), 223-231).
The 35 U.S.C. 103 rejection over Boni was previously discussed.
Additionally, Boni taught water [col 14, line 40], amphotericin B (previously discussed) and liposomes comprising HSPC [col 4, line 47], cholesterol (previously discussed) and DSPG [col 4, line 64]. Boni taught administration for inhalation, by aerosol (previously discussed) [col 4, lines 1-5].
Boni disclosed alpha-tocopherol, as used to form liposomes, whereby the alpha-tocopherol reduced the toxicity of the enclosed agents [col 6, lines 47-56]. However, Boni did not specifically teach alpha-tocopherol. Furthermore, although Boni taught liposomal formation, Boni was silent sucrose and disodium succinate hexahydrate, as recited in claim 41.
Nevertheless, Adler-Moore taught liposomal formulations of amphotericin B [title and abstract], where AmBisome was a commercially available formulation comprising [Table 1] amphotericin B, sucrose, HSPC, DSPG, cholesterol, alpha-tocopherol and disodium succinate hexahydrate. AmBisome reduced toxicity, thereby minimizing the adverse effects of AmB on host tissues [page 224, 2nd and 3rd full paragraphs].
Since Boni taught liposomal formulations of amphotericin B, whereby liposomes with reduced toxicity of the enclosed agents were suggested, it would have been prima facie obvious to one of ordinary skill in the art to include AmBisome within the teachings of Boni. An ordinarily skilled artisan would have been motivated to include commercially available liposomal formulations of amphotericin B with reduced toxicity, thereby minimizing the adverse effects of AmB on host tissues, as taught by Adler-Moore [Adler-Moore page 224, 2nd and 3rd full paragraphs].
Claim(s) 55-59 are rejected under 35 U.S.C. 103 as being unpatentable over Boni et al (USP 7,544,369 B2) in view, each, of Burke et al (WO 2016/073462 A1), and of Veit et al (Sci Transl Med, 2014, 6(246)).
The 35 U.S.C. 103 rejection over Boni was previously described.
Although Boni taught treating CF patients, as discussed, Boni was silent patients with F508∆ gene mutations, as recited in claims 55-58; refractory to treatment with ivacaftor, as recited in claim 59.
Burke disclosed methods for treating CF comprising administering, to a subject in need thereof, a therapeutically effective amount of AmB [abstract]. Burke showed that AmB restored normal apical surface liquid volume (e.g., an important marker for physiology in CF cell line epithelial monolayers), in CFTR-deficient human lung epithelia (e.g., cell lines derived from a patient with the most common F508∆/ F508∆ mutation) [Example 8].
Veit disclosed that most CF patients carry the ΔF508 mutation, which impairs CFTR folding, processing, function, and stability [abstract].
Since Boni generally taught treating CF patients with AmB, it would have been prima facie obvious to one of ordinary skill in the art to include, within the teachings of Boni, patients with the F508∆/ F508∆ mutation. The ordinarily skilled artisan would have been motivated to treat the most common mutation of CF, as taught by the combination of Burke [abstract, Example 8] and Veit [abstract].
Generally, 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. The idea for combining them flows logically from their having been individually taught in the prior art. See MPEP 2144.06. In the instant case, it is prima facie obvious to combine the active ingredients of Boni’s (AmB) and Burke’s compositions (AmB), in order to form a composition with active agents for the treatment of CF, since each were individually taught in the prior art, generally for the treatment of CF patients (Boni), and specifically for the treatment of F508∆/ F508∆ CF patients (Burke).
Regarding claim 59, Boni did not teach CF refractory to treatment with ivacaftor; however, Veit taught [abstract] that studies in ∆F508 CF patients indicated little clinical benefit of monotherapy with ivacaftor, whereas combination clinical trials showed limited, but significant, improvements in lung function. It would have been prima facie obvious to one of ordinary skill in the art to include, within the combined teachings of the art, CF refractory to treatment with ivacaftor, as taught by Veit. The ordinarily skilled artisan would have been motivated to study CF treatment, thereby optimizing and maximizing the clinical benefit of combination therapy, as taught by Veit at the abstract.
Nonstatutory Double Patenting
A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 31-32, 38, 41-42 and 46-61 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12,090,164.
Claims 31-32, 38, 41-42 and 46-61 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,850,256.
Although the claims at issue are not identical, they are not patentably distinct from each other because the species (genotype-agnostic rescue of cystic fibrosis) recited in the claims of the issued patents fall within the genus (method of treating cystic fibrosis) recited in the claims of the instant application, and thus read on) the instant claims.
Claims 31-32, 38, 41-42 and 46-61 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 11, 26-30 and 126-132 of copending Application No. 18/886,316.
Although the claims at issue are not identical, they are not patentably distinct from each other because the species (genotype-agnostic rescue of cystic fibrosis) recited in the copending claims fall within the genus (method of treating cystic fibrosis) recited in the claims of the instant application, and thus read on the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/CELESTE A RONEY/Primary Examiner, Art Unit 1612
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