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 1-38 are cancelled.
Claims 39-58 are pending and presented for examination on the merits.
Priority
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Information Disclosure Statement
The information disclosure statement (IDS) submitted on 6/18/25 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. See page 29, references 4, 5, 7, 9, 8, 10, 11, 12; Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The disclosure is objected to because of the following informalities: On pages 18, 21, 25, and 26; the following error messaging is unclear:
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.
Appropriate correction is required.
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.
Claim 46 is 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.
Regarding claim 46, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
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 39-53 are rejected under 35 U.S.C. 103 as being unpatentable over Bystrom et al. (WO9619199) and Vanderbist et al. (EP2050437) and Yadidi (WO2015127315).
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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Claim interpretation: the limitation of “wherein the composition is made by co-milling” is a product-by-process limitation. Please note that in product-by-process claims, “once a product appearing to be substantially identical is found and a 35 U.S.C. 102/103 rejection [is] made, the burden shifts to the applicant to show an unobvious difference.” See MPEP 2113 Product-by-Process Claims [R-08.2017]
I. PRODUCT-BY-PROCESS CLAIMS ARE NOT LIMITED TO THE MANIPULATIONS OF THE RECITED STEPS, ONLY THE STRUCTURE IMPLIED BY THE STEPS
“[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
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 scientist who researches drug particle composites for inhalation requires multidisciplinary expertise in aerodynamic particle science, materials engineering, and pulmonary pharmacokinetics to design powders that deposit effectively in the lungs. Such an artisan is aware of conventional excipient selection to optimize stability and flow as well as conventional production techniques to produces composites with architecture for the best aerodynamics.
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 39, 44, 45 and 49, Bystrom et al. teach a pharmaceutical composition comprising a single phase of discrete particles of a biologically active component and a lipid or mixture of lipids (Claims 1 and 8-10) comprising cholesterol and soybean phosphatidylcholine (Claim 3). Bystrom et al. teach adding a pharmaceutically acceptable carrier (Claim 26) that can be crystalline lactose monohydrate (Claim 28) or selected from glucose, fructose, galactose, trehalose, sucrose, maltose, raffinose, maltitol, melezitose, stachyose, lactitol, palatinate, starch, xylitol, mannitol, myoinositol, and hydrates thereof, and amino acids (Claim 29), which renders obvious a composition comprising cholesterol with carrier mannitol or trehalose. Bystrom et al. teach that the term “single phase” means that there is no separate crystalline phase of either active component or lipid in the powder of the present invention. (Page 3, lines 28-30). That is interpreted to mean that the scope of Bystrom et al. includes active pharmaceutical ingredients present in crystalline form.
Regarding claims 40-43, Bystrom et al. teach a mass median diameter of less than 10 microns (Claim 31), and where at least 90% of the powder particles have a diameter of less than 10 microns (Claim 20), for example 0.1-6 microns (Claim 22), thus having a particle size distribution of the discrete particles suitable for inhalation and a Dv90 as claimed. In fact, Bystrom et al. teach: “Where an additive, for example a carrier is present, the entire composition may be in the form of particles of a size within the respirable particle size range.” (Page 7, lines 24-25).
Regarding claim 46, Bystrom et al. teach adding non-glyceride lipids such as sphingomyelin (SM) and steroids (Claims 2-3 and 11-14; page 3, lines 16 through page 5, line 3).
Regarding claims 47 and 48, Bystrom et al. teach adding DPPC and DMPC (Claim 4) as well as lecithins (Page 4, lines 16-30).
Regarding claim 53, Bystrom et al. teach a dry powder inhaler with the composition (Claims 42-44).
Regarding claims 39 and 50-52, Vanderbist et al. teach a powder for use in dry inhalers (Abstract) and pharmaceutical powder compositions (Claims 1-23), and exemplify crystalline active ingredient tobramycin [0137] and not more than 10% by weight of carrier materials monosaccharides and disaccharides such as mannitol and lipids such as cholesterol, phospholipids and phosphatidylcholines and mixtures thereof (Claim 20) as well as lactose [0011, 0027, 0088-0089] in the form of discrete aerodynamic particles (Claims 8 and 42; [0011, 0048, 0152]). Vanderbist et al. teach that the powder contains at least 80% by weigh of the active compound (Claim 13) and not more than 10% by weight of carrier materials monosaccharides and disaccharides such as mannitol and lipids such as cholesterol, phospholipids and phosphatidylcholines and mixtures thereof (Claim 20) as well as lactose [0011, 0027, 0088-0089].
Regarding claim 39-52, Yadidi teaches dry powder formulations for inhalation with a MADD within a range of about 0.5 to about 10 microns with a phospholipid in an amount ranging from about 0.1 to about 10% w/w of the particles (Title; Abstract; Claim 1) and a Dv90 of less than about 10 microns or about 6 microns (Claim 3-4). Yadidi teaches that the phospholipid includes DPPC or DSPC (Claims 8-9) or other phospholipids such as DMPC or even sphingomyeline or ceramides or lecithin [0193-0194]. Yadidi teaches that addition of one or more excipients such as sugars/sugar alcohols excipients including lactose or mannitol or trehalose [0192]. Yadidi teaches that such excipients can be present from about 0% to about 99% or from about 0.1% to about 40% or 0.5% to about 20% even from about 1% to about 5% [0196, 0316]. Yadidi teach jet-milling to reduce the particle size [0247].
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 Bystrom et al. is that Bystrom et al. do not expressly teach a pharmaceutical composition wherein said sugar in an amount of from 0.5 to 45 wt% by weight of the total composition or wherein the weight % of the components by weight of the total composition ranges as follows: API from 50 to 99.5 wt%; sugar from 0.5 to 45 wt%; and lipid from 0.01 to 5 wt% or API from 80 to 99.5 wt%; sugar from 0.5 to 20 wt %; and lipid from 0.04 to 2 wt% or wherein the API is present at 30 wt% or more. This deficiency in Bystrom et al. is cured by the teachings of Vanderbist et al. and Yadidi.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to make the pharmaceutical composition of Bystrom et al. wherein said sugar in an amount of from 0.5 to 45 wt% by weight of the total composition or wherein the weight % of the components by weight of the total composition ranges as follows: API from 50 to 99.5 wt%; sugar from 0.5 to 45 wt%; and lipid from 0.01 to 5 wt% or API from 80 to 99.5 wt%; sugar from 0.5 to 20 wt %; and lipid from 0.04 to 2 wt% or wherein the API is present at 30 wt% or more, as suggested by Bystrom et al., Vanderbist et al. and Yadidi, and produce the instant invention. One of ordinary skill in the art would have been motivated to do this because for the following sound articulated reasoning with rational underpinning based upon the evidence. Bystrom et al. teach that: “The amount of additives present in the formulation may vary over a very wide range. In some circumstances little or no additive may be required…The percentage of additives may also be dependant[sic] on the potency of the biologically active compound and the optimal amount of powder for inhalation.” (Page 7, lines 15-17 and 21-22). That provides motivation for optimization and Yadidi expressly teaches that such excipients can be present from about 0% to about 99% or from about 0.1% to about 40% or 0.5% to about 20% even from about 1% to about 5% [0196]. The analogous art of Vanderbist et al. teach compositions with 80% by weight active compound in the powder and 10% by weight of a carrier material that includes sugars, cholesterol and phospholipids. It is the merely routine optimization of the composition of Bystrom et al., in view of Vanderbist et al. and Yadidi, to arrive at a pharmaceutical powder composition having the same DV90 as claimed and comprising the sugar in an amount of from 0.5 to 45 wt% by weight of the total composition; wherein the weight % of the components by weight of the total composition ranges as follows: API from 50 to 99.5 wt%; sugar from 0.5 to 45 wt%; and lipid from 0.01 to 5 wt% or API from 80 to 99.5 wt%; sugar from 0.5 to 20 wt %; and lipid from 0.04 to 2 wt% and wherein the API is present at 30 wt% or more with a reasonable expectation of success. Especially when Bystrom et al. teach and suggest optimization of the powder for inhalation. 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)…see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("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 54-58 are rejected under 35 U.S.C. 103 as being unpatentable over Morton et al. (US20080127972) and Vanderbist et al. (EP2050437).
Applicant claims:
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Determination of the scope and content of the prior art
(MPEP 2141.01)
Regarding claim 54, which includes the limitations of claim 39, Vanderbist et al. teach a powder for use in dry inhalers (Abstract), methods for manufacturing the powder composition [0001, 0037] and pharmaceutical powder compositions (Claims 1-23), and exemplify crystalline active ingredient tobramycin [0137] and carrier materials monosaccharides and disaccharides such as mannitol and lipids such as cholesterol, phospholipids and phosphatidylcholines and mixtures thereof (Claim 20) as well as lactose [0011, 0027, 0088-0089] in the form of discrete aerodynamic particles (Claims 8 and 42; [0011, 0048, 0152]). Vanderbist et al. teach that the powder contains at least 80% by weigh of the active compound (Claim 13) and not more than 10% by weight of carrier materials monosaccharides and disaccharides such as mannitol and lipids such as cholesterol, phospholipids and phosphatidylcholines and mixtures thereof (Claim 20) as well as lactose [0011, 0027, 0088-0089].
Regarding claims 54 and 56, Vanderbist et al. suggest jet-milling to modify the physical properties of the powder [0033, 0037].
Regarding claim 53, Morton teaches methods of processing particles to form dry powder formulations that exhibit excellent powder properties (Abstract; claims 1-10). In Example 2, Morton prepared blends of active budesonide with fine lactose and magnesium stearate using Mechanofusion of all three components together (Example 2 [0094-0098]/ Morton instructs: “It is also known that intensive co-milling of micronized drug particles with additive material may be carried out in order to produce composite particles. This co-micronisation can improve dispersibility, as disclosed in the earlier patent application published as WO 02/43701.” ([0026; see also [0033-0034, 0036]). Morton teaches: “The term co-milling is used herein to refer to a range of methods, including co-micronising methods, some examples of which are outlined below. In the prior art, co-milling or co-micronising active agents or excipients with additive materials has been suggested.” [0057]. It is the Examiner’s position that co-milling simultaneously blends the API and one or more excipients (step a) and reduces the particle size distribution of the blend (step b).
Regarding claim 55-56, Morton teaches MechnoFusion which is a solventless dry process [0059, 0066-0067] as well as Hybridiser method where powder is fed into the Hybridiser and subjected to ultra-high impact [0069], which is solventless, as well as jet-milling to pulverize particles [0070, 0072, 0076], which is an attractive process for co-milling active and additive particles [0080]. Morton expressly teaches: “A further benefit associated with the present invention is that the powder processing steps do not have to involve organic solvents.” [0077]. Morton teaches that different combinations of co-milling can be used [0083-0084] or even simply co-milling the active material and additive material at a high grinding pressure [0086].
Regarding claim 58, Morton do not teach a conditioning step1 as defined by the instant specification and the limitation of wherein a reduced amount of conditioning time is employed when compared with the conditioning time required to condition a composition comprising micronized API alone appears implicit in the method of Morton.
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 Morton is that Morton do not expressly teach the pharmaceutical composition of claim 39 where the lipid comprises cholesterol in a method of blending API and one or more excipients comprising at least one sugar or at least one lipid, or both at least one sugar and at least one lipid, into a homogeneous powder; b. Reducing the particle size distribution of the blend; wherein the composition is made by co-milling and wherein the API and at least one sugar are first blended and jet-milled together, and at least one lipid is then blended and jet-milled with the resulting pharmaceutical composition, yielding a pharmaceutical composition comprising API, at least one sugar and at least one lipid. This deficiency in Morton is cured by the teachings of Vanderbist et al.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to perform the instantly claimed process by using the solventless jet-milling/co-milling process of Morton to make dry powder for inhalation of Vanderbist et al. having a crystalline API, sugar and cholesterol lipid wherein the sugar in an amount of from 0.5 to 45 wt% by weight of the total composition and produce the instant invention. One of ordinary skill in the art would have been motivated to do this because for the following sound articulated reasoning with rational underpinning based upon the evidence. The solventless co-milling/jet-milling process of Morton is open to any active and combination of excipients. The art of Vanderbist et al. renders obvious the powder having a crystalline API, sugar and cholesterol lipid wherein the sugar in an amount of from 0.5 to 45 wt% by weight of the total composition. It is then obvious to blend the crystalline API of Vanderbist et al. with one or more excipients comprising at least one sugar or at least one lipid such as cholesterol or both at least one sugar and at least one lipid such as cholesterol into a homogenous powder by co-milling/jet-milling that reduces/micronizes the particle size distribution of the blend. Since Morton teaches embodiments where simply co-milling the active material and additive material at a high grinding pressure [0086] and embodiments where the process can be broken into steps (Claims 1-10). In fact, Morton suggests taking the composite particles produced by the two-step process and introduce additive material into the particles by MechnoFusion [0088]. Thus, it is merely the artisan selection of first blending and jet-milling the API and at least one sugar and then adding at least one lipid to the API and at least one sugar and blending with jet-milling. The net result appears the same of producing a pharmaceutical composition comprising API, at least one sugar and at least one lipid.
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.
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.
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, 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 The specification teaches: “In the process of the invention, one advantage is that it is possible to dispense with a conditioning step. In a typical conditioning step, formulations during their manufacture are stored under controlled conditions of temperature and relative humidity.” (Page 14).
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