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 .
Claim Status
Claims 2, 3, 10, 11, 20-28, 31, 33, 35 and 37-43 are cancelled.
Claims 1, 4-9, 12-19, 29, 30, 32, 34 and 36 are pending and under examination.
Withdrawn rejections
Applicant's amendments and arguments filed 3/12/26 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or objection not specifically addressed below is herein withdrawn. Claims 1, 4-9, 12-19, 29-30, 32, 34, and 36 were rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. Claims 1, 4-9, 12-19, 29-30, 32, 34, and 36 were rejected under 35 U.S.C. 103 as being unpatentable over Vanderbist et al. (WO 2009/050217 A2, Published 04/23/2009) (hereinafter Vanderbist) in view of Smyth et al. (WO 2019/070693 A1, Published 04/11/2019) (hereinafter Smyth) and Bannigan et al. (Investigation into the Solid and Solution Properties of Known and Novel Polymorphs of the Antimicrobial Molecule Clofazimine, Published 11/07/2016) (hereinafter Bannigan). Applicant’s amendments and arguments are persuasive. A search update and IDS review by the new Examiner of record has resulted in the rejection below.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
Claim Rejections - 35 USC § 112
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 30, 32 and 34 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. Claim 30 states: “wherein the composition is administered before, simultaneously or subsequently to the administration of an agent”. Applicant is claiming activities of a user with the composition in a composition of matter claim. (See the analogous situation in MPEP 2173.05(p)(II): “A single claim which claims both an apparatus and the method steps of using the apparatus is indefinite under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. See In re Katz Interactive Call Processing Patent Litigation, 639 F.3d 1303, 1318, 97 USPQ2d 1737, 1748-49 (Fed. Cir. 2011).”) That is impermissible and indefinite. Dependent claims are rejected as indefinite because they are dependent upon an indefinite base claim. These claims will not be further treated on the merits.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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, 4-9, 12-19, 29 and 36 are rejected under 35 U.S.C. 103 as being unpatentable over Keswani et al. (US20160220710; of record) and Bannigan et al. (Cryst. Growth Des. 2016, 16, 7240−7250; or record).
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103, the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103.
Applicant claims, for example:
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Level of Ordinary Skill in the Art
(MPEP 2141.03)
MPEP 2141.03 (I) states: “The “hypothetical ‘person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988). The level of skill is that of a pharmaceutical formulation research scientist with knowledge of formulations for dry powder inhalation, as is the case here, then one can assume comfortably that such an educated artisan will draw conventional ideas from particle formulation engineering, carrier selection of excipients for flowability and powder stability, aerosol physics and inhalation techniques/devices for administration1— without being told to do so.
In addition, the prior art itself reflects an appropriate level (MPEP 2141.03(II)).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Regarding claims 1, 5, 16-18 and 29, Keswani et al. teach a composition comprising clofazimine crystals with a monoclinic, triclinic or orthorhombic structural form (Claims 1 and 4-6; [0009]), hence polymorphs of clofazimine, where the crystals have a size of 0.001-20 µm (Claim 8) and is in a complex with a salt (Claim 2) and in the form of a powder for a metered inhaler or a dry powder inhaler [0153-0155]. Keswani et al. teach: “The dose when using the compounds and formulations described herein can vary within wide limits and as is customary and is known to the physician, it is to be tailored to the individual conditions in each individual case. It depends, for example, on the nature and severity of the illness to be treated, on the condition of the patient, on the compound employed or on whether an acute or chronic disease state is treated or prophylaxis is conducted or on whether further active compounds are administered in addition to the compounds. Representative doses include, but not limited to, about 0.001 mg to about 5000 mg, about 0.001 mg to about 2500 mg, about 0.001 mg to about 1000 mg, 0.001 mg to about 500 mg, 0.001 mg to about 250 mg, about 0.001 mg to 100 mg” [0135]. Keswani et al. teach: “The amount of active ingredient, or an active salt or derivative thereof, for use in treatment will vary not only with the particular salt selected but also with the route of administration, the nature of the condition being treated and the age and condition of the patient and will ultimately be at the discretion of the attendant physician or clinician.” [0136]. Keswani et al. teach: “A representative amount in a powder or tablet may contain from 0.5 to about 90 percent of the active compound; however, an artisan would know when amounts outside of this range are necessary. Suitable carriers for powders and tablets are magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, a low melting wax, cocoa butter and the like.” Those pharmacologically inert excipients would be physiologically acceptable. Thus, the amount of active compound overlaps the claimed amount of about 30% and about 75 mg of clofazimine and the size of the clofazimine crystal particles overlaps the median particle size of less than 5 microns. MPEP 2144.05(I): In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976).
Regarding claims 7-9 and 29, Keswani et al. teach a particle size of 50 microns or less [0154] and where the crystals have a size of 0.001-20 µm (Claim 8), which overlaps the claimed mass median aerodynamic diameter of less than 5 microns and between 1-3 microns, and that a finely divided solid mixture with the carrier [0140], which would be homogenous.
Regarding claims 12-15, Keswani et al. teach adding phospholipids (Claim 14), surfactants [0153], the amino acid glutamic acid [0158], and polymers [0155].
Regarding claim 19, the intended use of the composition for use in the treatment and/or prophylaxis of pulmonary infections caused by mycobacteria or other gram positive bacteria is implicit in the composition of Keswani et al. The limitation has been considered but is not given patentable weight. An intended use will not limit the scope of the claim because it merely defines a context in which the invention operates. Boehringer Ingelheim Vetmedica, Inc. v. Schering-Plough Corp., 320 F.3d 1339, 1345 (Fed. Cir. 2003).
Further regarding claim 29, Keswani et al. teach blister packs and capsules for the powder [0155], thereby teaching a system for use in in providing antibiotic activity when treating or providing prophylaxis against a pulmonary infection caused by mycobacteria or other gram positive bacteria. See intended use discussion above.
Regarding claim 36, Keswani et al. teach methods of treating a disease in a subject by administering the composition to a subject diagnosed with the disease (Claim 15) caused by Mycobacterium or gram positive S. Aureus (Claim 17) by inhalation [0153].
Regarding claims 1, 4, 29 and 36, Bannigan et al. teach polymorphic forms of clofazimine including FI, FII and FIII (Abstract; Page 7241, Crystal growth) and that clofazimine “has also shown good in vitro activity against other members of the mycobacterium family, both slow and fast growing species, as well as activity against most other Gram positive bacteria species” (Page 7240, left column).
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02) and Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
The difference between the instant application and Keswani et al. is that Keswani et al. do not expressly teach clofazimine polymorphic forms FI, FII and FIII with excipients in the form of coarse particles. This deficiency in Keswani et al. is cured by the teachings of Bannigan et al. However, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use clofazimine polymorphic forms FI, FII and FIII, as suggested by Bannigan et al., with excipients in the form of coarse particles, and produce the instant invention. One of ordinary skill in the art would have been motivated to do this because Keswani et al. direct the artisan to employing polymorphic forms of clofazimine and Bannigan et al. teach the claimed polymorphic forms of clofazimine. The artisan would do so with a reasonable expectation of success. Regarding the limitation of the excipient(s) being in the form of coarse particles, since Keswani et al. teach and suggest the same excipients claimed, then it would appear that the excipients taught by Keswani et al. are also provided in the form of coarse particles. Especially when no degree of coarseness is defined by the claim.
Furthermore, it is merely routine optimization to obtain any of the claimed particle sizes based on the discloser of Keswani et al. See MPEP 2144.05 (II) (A): “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Accordingly, in view of the combined references, the ordinary artisan would have a reasonable expectation of success in obtaining the claimed pharmaceutical composition for dry powder inhalation comprising the claimed clofazimine polymorphs, coarse excipients and finely divided mass median aerodynamic diameter particle sizes and a system for use in providing antibiotic activity when treating or providing prophylaxis against a pulmonary infection caused by mycobacteria or other gram positive bacteria, wherein the system comprises:
1) a dry powder pharmaceutical formulation comprising:
a) about 75 mg of clofazimine polymorphic orthorhombic form FIii, and
b) lactose;
2) a container for the formulation selected from a capsule or blister package, and
3) a dry powder inhaler,
wherein the clofazimine is about approximately 30% of the formulation by weight and is present in the form of a dry powder, and wherein clofazimine containing particles have a mass median diameter of 1 to 5μm.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the combined references, especially in the absence of evidence to the contrary.
Response to Arguments:
Applicant’s arguments filed 3/12/26 are directed to a withdrawn rejection.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNST V ARNOLD whose telephone number is (571)272-8509. The examiner can normally be reached M-F 7-3:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian Y Kwon can be reached at 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERNST V ARNOLD/Primary Examiner, Art Unit 1613
1 See for example Piyush Mehta “Dry Powder Inhalers: A Focus on Advancements in Novel Drug Delivery Systems” Journal of Drug Delivery Volume 2016 article ID 8290963; 17 pages.
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