-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 .
Applicant’s response dated October 31, 2025 is acknowledged.
Priority
This application is a 371 of PCT/CN2020/094293 filed on 06/04/2020, and claims foreign priority in CN2019 10559969.5 filed on 06/26/2019.
Claim Status
Claims 1, 8-10, and 12-18 are pending. Claims 15-18 are withdrawn. Claims 1, 8-10, and 12-14 are examined. Claims 2-7 and 11 were canceled. Claim 1 was amended.
Maintained Claim Rejections — 35 USC § 103
Modified as Necessitated by Amendment
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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 8, 9, and 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Muhrer (US 2010/0247658 Al Published September 30, 2010 “Muhrer 1”), Ruecroft et al. (US 2011/0146678 Al Published June 23, 2011 “Ruecroft”), Muhrer (US 2010/0266696 Al Published October 21, 2010 “Muhrer 2”), Ruecroft (US 2014/0228330 Al Published August 14, 2014 “Ruecroft 1”), and Staniforth (WO 2004/093848 A2 Published November 4, 2004).
The claims encompass a preparation method of pharmaceutical inhalation aerosol, wherein the method comprises steps 1, 2, and 3.
The teachings of Muhrer 1 are related to a process for reducing the tendency of a drug substance to aggregate and/or agglomerate during storage. The process involves micronizing the drug substance to give a mean particle size of less than about 10 microns, and exposing the micronized drug substance to dry environment at elevated temperature between 40°C and 120°C for at least six hours (Abstract and paragraphs 0007-0009). The drug substance may be micronized together or co-micronized with one or more other drug substances and/or one or more anti-adherent agents (paragraph 0010). Preferred drug substance is glycopyrronium (paragraph 0014), including glycopyrronium bromide (paragraph 0022). A second embodiment includes an inhalable dry powder formulation that contains a drug substance that has been treated using the aforementioned process (paragraph 0015). A third embodiment relates to an inhalable formulation that contains a drug substance suspended in propellant (paragraph 0016). The drug substance can be any pharmacologically active ingredient for administration by inhalation (paragraph 0026). Such drug substances include indacaterol (paragraph 0027). Paragraph 0033 further defines particle size ranges suitable for inhalation. Micronizing equipment is well known in the art and includes a variety of grinding and milling machinery, for example compressive- type mills such as mechanofusion mills, impact mills such as ball mills, homogenizers and microfluidizers, and jet mills (paragraph 0034).
Muhrer 1 does not teach the particle size of glycopyrronium bromide and indacaterol prior to micronization, feed rate of drug mixture, and particle size distribution of micronized drug mixture.
The teachings of Muhrer 2 are related to process of preparing a particulate and substantially crystalline drug substance. The process involves suspending a substantially crystalline drug substance in an anti-solvent to give a suspension, homogenizing the suspension
at elevated pressure to vie drug particles that have a mean particle size of less than about 10 microns (Abstract). When preparing a drug substance for formulation and administration by inhalation, freshly prepared drug substance, often in the form of coarse grains, is commonly micronized i.e. mechanically pulverized to give particles whose mean particle size is suitable for inhalation. That mean particle size is typically less than 10 microns, preferably less than 5 microns, in mean diameter and the micronization process is usually an air-jet-milling process (paragraph 0002). The drug substance encompasses combinations of drugs including glycopyrrolate bromide and indacaterol (paragraphs 0029-0038). Coarse glycopyrrolate is in the form of irregular crystals of about 50-100 microns. Product quality and particle size changes radically during homogenization step with morphology of glycopyrrolate changing from large, irregular size crystallites to more compact, platelet-like particles with an average size markedly below 5 microns. Laser light diffraction particle size analysis reveals a x50 mean particle size of 1.3 microns, x10 mean particle size of 0.6 microns, and x90 mean particle size of 3.1 microns (paragraph 0062).
The teachings of Staniforth are related to pharmaceutical dry powder formulations administered by pulmonary inhalation (Abstract). Suitable active agents include anticholinergic agents such as glycopyrrolate (page 10 line 31-32) and pharmaceutically acceptable salts thereof (page 11 line 28). A plurality of active agents may be used (page 11 lines 31-32). In preferred embodiments, the active agent is glycopyrrolate (page 12 lines 1-2). The formulation is delivered with a dry powder inhaler device (page 12 lines 9-17). Milling can be used to substantially decrease the size of particles of active agents. However, if the particles of active agent are already fine, for example a MMAD of less than 20 microns prior to the milling step, the size of those particles may not be significantly reduced where the milling of these active particles takes
place in the presence of an additive material. (paragraph bridging pages 112-113). Co-jet milling may be carried out at grinding pressure between 0.1 and 12 bar. Varying the pressure allows one to control the degree of particle size reduction. At pressures in the range of 0.1-3 bar, the co-jet milling will primarily result in blending of the active and additive particles. At 3-12 bar, the co- jet milling will additionally lead to particle size reduction (page 124 lines 18-23). Page 148 teaches co-jet milling conditions where formulations 14 and 15 were produced by passing a drug through a micronizer three times, each time with an injector air pressure of 8 bar, grinding air pressure of 1.5 bar and powder feed rate of about 1 g/minute (lines 15-23).
Muhrer 1, Muhrer 2, and Staniforth do not teach claimed step 3.
The teachings of Ruecroft are related to a process for increasing the level of crystallinity and modifying surface characteristics in an amorphous solid material (paragraph 0001); and production of active drug particles that are to form a dry powder formulation intended for administration to the lung using a dry powder inhaler device (paragraph 0002). A suitable combination of particles of active ingredients includes glycopyrronium bromide and indacaterol (paragraph 0100). The formulation is filled into a canister such as an aluminum can which is closed with a metering valve. The metering valve is designed to deliver a metered amount of the formulation per actuation and incorporate a gasket to prevent leakage of propellant through the valve (paragraph 0159). Propellant includes HFA 134 a, HFA 227 or mixtures thereof (paragraph 0158).
Muhrer 1, Muhrer 2, Staniforth, and Ruecroft do not teach suitable weight ratios of glycopyrronium bromide and indacaterol.
The teachings of Ruecroft 1 are related to pharmaceutical compositions comprising a eutectic composition of two pharmaceutically active ingredients for delivery to the lung by
inhalation (Abstract). Preferred combinations of a beta 2 agonist and an anticholinergic include indacaterol maleate and glycopyrronium bromide (paragraph 0067). Preferred range of molar ratios of a beta 2 agonist and an anticholinergic is 10:1 to 1:10 (paragraph 0068).
The teachings of Muhrer 1, Muhrer 2, Staniforth, Ruecroft, and Ruecroft 1 are related to pharmaceutical compositions comprising glycopyrronium bromide, wherein the compositions are intended to be administered by inhalation, and it would have been obvious to have combined their teachings because they are in the same field of endeavor.
Regarding claim 1, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have prepared a pharmaceutical inhalation aerosol comprising mixing glycopyrronium bromide with indacaterol to obtain a mixture, micronizing the mixture with a jet mill to obtain a micronized mixture having a mean particle size of less than 10 microns, and suspending the micronized mixture in a propellant and placing in a metered dose inhaler, with a reasonable expectation of success because Muhrer 1 teaches a method of preparing a pharmaceutical inhalation aerosol comprising mixing glycopyrronium bromide with indacaterol to obtain a mixture, micronizing the mixture with a jet mill to obtain a micronized mixture having a mean particle size of less than 10 microns, and suspending the micronized mixture in a propellant and placing in a metered dose inhaler. Muhrer 1 teaches co-micronizing the drugs, thus it would have been obvious to have formed a mixture of the drugs prior to micronizing.
Muhrer 1 teaches that the preferred mean particle size is less than 5 microns and that mean particle size in the range of about 2 microns to about 5 microns will generally be deposited in the respiratory bronchioles whereas smaller particles are likely to be exhaled (paragraph
0033). Muhrer 1 does not teach a D90, D50, and D10 distribution of the micronized particles. It would have been obvious to have looked to the teachings of Muhrer 2 for a distribution of particles because Muhrer 2 teaches a powder composition intended for inhalation having a x50 mean particle size of 1.3 microns, x10 mean particle size of 0.6 microns, and x90 mean particle size of 3.1 microns (paragraph 0062). It would have been obvious to have formed the powder composition of Muhrer 1 having a D90, D50, and D10 distribution as taught by Muhrer 2 because Muhrer 2 teaches said distribution as suitable for drugs intended for administration via inhalation. The selection of a known particle size range based on its suitability for its intended purpose supports obviousness.
D90 ranges 2.86-4.18, 2.86-3.58, and 2.86-3.40 microns in claims 1, 12, and 13 are obvious because the ranges encompass 3.1 microns.
D50 ranges 1.42-1.86, 1.42-1.68, and 1.42-1.53 microns in claims 1, 12, and 13 are obvious because 1.42 is close enough to 1.3 microns that a person skilled in the art would have expected them to have the same properties. The specification was reviewed and there is no evidence that the claimed particle distribution is critical.
D10 ranges 0.58-0.66, 0.58-0.62, and 0.58-0.61 in claims 1, 12, and 13, are obvious because the ranges encompass 0.6 microns.
Muhrer 1 does not teach the particle size of the drug particles prior to micronizing. Considering that Muhrer 1 modified by Muhrer 2 requires the micronized drugs to have a D90 of 3.1 microns, D50 of 1.3 microns, and D10 of 0.6 microns, the skilled artisan would have understood that the starting drug particle size range would have to be greater than the particle size range after micronization because micronization is a process of reducing particle size. It would have been prima facie obvious to have utilized coarse particles of glycopyrronium
bromide and indacaterol having a size of 50-100 microns to form micronized drug particles having a D90, D50, and D10 as shown above, with a reasonable expectation of success because Muhrer 2 teaches using coarse drug particles comprising glycopyrronium bromide and indacaterol and micronizing said particles to form micronized drug particles having a particle size of less than 10 microns. It would have been further obvious to have used glycopyrronium bromide and indacaterol fine particles having a particle size of less than 20 micron prior to micronization, with a reasonable expectation of success because Staniforth teaches co-jet milling method of drug particles such as glycopyrronium bromide to form a drug formulation suitable for inhalation where the drug particles prior to micronization have a fine particle size of less than 20 microns. It was known in the art that micronization of drug particles may be performed on coarse drug particles (50-100 microns) or fine drug particles (less than 20 micron). It would have been obvious to have practiced Muhrer 1’s method using coarse particles of the two drugs, fine particles of the two drugs, or a combination fine particles and coarse particles where one drug is coarse and the other fine, with a reasonable expectation of success because Muhrer 2 showed that micronization of coarse particles produces particles suitable for inhalation and Staniforth teaches that micronization of fine particles produces particles suitable for inhalation. The claimed particle size of coarse particles is obvious because 50-100 microns overlaps with D90>10 microns, and the claimed particle size range of fine particles is obvious because less than 20 microns overlaps with D90<5 microns. The specification was reviewed and there is no evidence that claimed combination of fine and coarse drug particles is critical and there is no evidence that claimed particle size distributions prior to micronization are critical.
Muhrer 1 does to teach the feed rate of the drug mixture. It would have been obvious to have added the drug mixture to the jet mill at rate of about 1 g/min, with a reasonable
expectation of success because Staniforth teaches examples of micronizing a drug powder using a jet mill by feeding the drug powder at a rate of about 1 g/min. It would have been obvious to have varied the feed rate of the drug powder because Staniforth teaches that increasing powder feed rate from 1 to 10 g/min resulted in larger particles (page 151 lines 12-13), and that the feed rate for the jet mills depends on their size where small spiral jet mills might use a feed rate of 1-2 g/min, whereas industrial scale mills will have a feed rate in the order of kg/hr (page 155 lines 15-21). In view of these teachings, it would have been obvious to vary the feed rate in order to obtain a micronized drug particle mixture having D90, D50, and D10 as described above. The skilled artisan would have arrived at the claimed feed rate of 0.5 g/min through routine experimentation. The feed rate in claim 1 is obvious because a person skilled in the art would have arrived the claimed feed rate through routine experimentation. It was known from Staniforth that increasing feed rate from 1 to 10 g/minutes results in larger particles, therefore the skilled artisan would have understood that lower feed rate would result in smaller particles. The specification was reviewed and there is no evidence that the claimed feed rate is critical.
It would have been prima facie obvious to a person skill in the art before the effective filing date of the claimed invention to have varied the micronization pressure in the range of 3-12 bar in Muhrer 1 method, with a reasonable expectation of success because it was known from Staniforth that 3-12 bar is a suitable micronization pressure when micronizing drugs intended for inhalation. The selection of a known method parameter suitable for its intended purpose supports obviousness. The claimed pressure range is obvious because it overlaps with 3-12 bar.
Muhrer 1 teaches suspending the micronized mixture in a propellant in a metered dose inhaler, but does not teach the details of a metered dose inhaler. It would have been obvious to
have added the micronized composition to an aluminum can, performed valve sealing, and filled with propellant, with a reasonable expectation of success because Ruecroft teaches filling an inhalable formulation into a canister such as an aluminum can which is closed with a metering valve, where the metering valve is designed to deliver a metered amount of the formulation per actuation and incorporate a gasket to prevent leakage of propellant through the valve. It is apparent from these teachings that the micronized composition and propellant are both added to the aluminum can and it would have been obvious to have added the two in any order. Valve sealing was performed because Ruecroft teaches incorporating a gasket to prevent leakage of propellant through the valve. The prior art composition reads on an aerosol because the micronized drug particles are suspended in a propellant gas.
Regarding mass ratio ranges in claim 1, it would have been prima facie obvious to a person skilled in the art before the effective filing date of the claimed invention to have further modified the method of Muhrer 1 in view of Ruecroft 1 by mixing indacaterol and glycopyrronium bromide in a range of molar ratios from 1:10 to 10:1, with a reasonable expectation of success because it was known from Ruecroft 1 that a range of molar ratios from 1:10 to 10:1 of a beta 2 agonist and an anticholinergic, such as indacaterol maleate and glycopyrronium bromide, is suitable for making a pharmaceutical composition intended for inhalation. Molecular mass of indacaterol is 392 g/mole and molecular mass of glycopyrronium bromide is 318 g/mole. A 10:1 to 1:10 range of molar ratios of indacaterol to glycopyrronium bromide is equivalent to range of weight ratios from 12:1 to 1:8. Claimed range of mass ratio is obvious because it overlaps with the prior art range of mass ratios.
Regarding claim 8, Muhrer 1 teaches a jet mill.
Regarding claim 9, it would have been obvious to have utilized HFA 134a, HFA 227, or a mixture thereof as the propellant, with a reasonable expectation of success because it was known from Muhrer 2 that propellants suitable for use in inhalable compositions include HFA 134a, HFA 227, or a mixture thereof.
Regarding claim 14, it would have been prima facie obvious to a person skill in the art before the effective filing date of the claimed invention to have varied the micronization pressure in the range of 3-12 bar in Muhrer 1 method, with a reasonable expectation of success because it was known from Staniforth 3-12 bar is a suitable micronization pressure when micronizing drugs intended for inhalation. The selection of a known method parameter suitable for its intended purpose supports obviousness.
It would have been prima facie obvious to a person skilled in the art before the effective filing date of the claimed invention to have further modified method of Muhrer 1 in view of Ruecroft 1 by mixing indacaterol and glycopyrronium bromide in a range of molar ratios from 1:10 to 10:1, with a reasonable expectation of success because it was known from Ruecroft 1 that a range of molar ratios from 1:10 to 10:1 of a beta 2 agonist and an anticholinergic, such as indacaterol maleate and glycopyrronium bromide, is suitable for making a pharmaceutical composition intended for inhalation. Molecular mass of indacaterol is 392 g/mole and molecular mass of glycopyrronium bromide is 318 g/mole. A 10:1 to 1:10 range of molar ratios of indacaterol to glycopyrronium bromide is equivalent to range of weight ratios from 12:1 to 1:8.
Claimed ranges of mass ratios are obvious because they overlap with the prior art range of mass ratios.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Muhrer 1, Muhrer 2, Ruecroft, Ruecroft 1, and Staniforth as applied to claims 1, 8, 9, and 12-14 above, and further in view of Snape (US 2008/0020048 Al Published January 2008).
The claim further defines step 3 in claim 1.
The teachings of Muhrer 1, Muhrer 2, Ruecroft 1, Ruecroft, and Staniforth are relied upon as summarized above. They do not teach the limitations of claim 10.
The teachings of Snape are related to glycopyrrate or an analogue thereof useful for the treatment of bronchospasms (Abstract). Controlled release formulations of glycopyrrolate are to be provided in a form suitable for delivery by inhalation. Devices and formulations suitable for delivery by inhalation are known to the skilled person. The composition may be prepared for delivery as an aerosol in a liquid propellant, for example for use in a pressurized metered dose inhaler (PMDI's). Propellants suitable for use in a PMDI are known to the skilled person, and include CFC-12, HFA-134a, HFA-227, HCFC-22 (difluorochloromethane), HFA-152 (difluoroethane and isobutane) (paragraph 0036).
The teachings of Snape and Muhrer 1 modified with Muhrer 2, Ruecroft 1, Ruecroft, and Staniforth are related to pharmaceutical compositions in the form of powder where the compositions are intended for inhalation and it would have been obvious to have combined them because they are in the same field of endeavor. It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified Muhrer 1 composition by using a mixture of propellants comprising HFA 134a, HFA 227, and HFA 152, with a reasonable expectation of success because Muhrer 1 teaches using mixtures of propellant gases and specifically use HFA 134a and HFA 227, and it was known
from Snape that HFA 134a, HFA 227, and HFA 152 are suitable propellants for compositions intended for inhalation.
Combining prior art elements according to known methods to obtain predictable results supports obviousness and the selection of a known material suitable for its intended purpose supports obviousness.
Response to Arguments
Applicant’s arguments submitted in the remarks dated April 18, 2025, were fully considered but are not persuasive for the following reasons.
On pages 5-6, applicant argued against Muhrer 1 by listing the claimed limitations that are not obvious over the reference and that the reference solves the problem of drug aggregation in inhalable dry powder formulation, which is different from applicant’s technical problem.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Present claims are rejected over a combination of references and not only Muhrer 1, thus it is irrelevant that Murher 1 does not teach all claimed limitations. All of the claimed limitation are obvious over Muhrer 1 modified by secondary references.
Applicant’s solution to a technical problem does not have to be the same as Muhrer 1’s solution to a technical problem for an obviousness rejection to be proper. Applicant’s solution to applicant’s technical problem is a not a claimed limitation, thus the rejection of claims does not have address a limitation that is not claimed. Office’s reasons for combining and modifying prior art references does not have be the same as applicant’s as long as claimed limitations are met. Claimed limitations are met by the combination of references as shown above, and it is irrelevant that the Office arrived at the claimed invention by combining the references for reasons different from applicant’s reasons.
On pages 6-8, the applicant stated that Muhrer 2 solves the problem of agglomeration caused by secondary crystallization due to water absorption after air-jet-milling of drug crystals by homogenizing the suspension, which is different from the inventive concept of the instant application. The reference and instant application solve a different technical problem and provide different solutions to those problems. It is not immediately obvious to combined Muhrer 1 and Muhrer 2 to solve the technical problem of the present application.
Muhrer 2 is relied upon for a particle size distribution that is suitable for administration by inhalation. Muhrer 2 also teaches suspending the drug in a propellant when the drug is intended for administering with a metered dose inhaler (paragraph 0058), which renders aerosol obvious. Applicant’s technical problem is a not a claimed limitation therefore the rejection does not address applicant’s technical problem. The Office does not have to use the same reason as applicant to modify and combine prior art references in order to arrive at applicant’s invention. The combination of prior art references meets all of the claimed limitations and motivation to combine prior art references does not have to be the same as applicant’s reason.
On pages 8-11, applicant argued that Staniforth’s invention concept is to provide a new type of dry powder inhaler device that can solve Staniforth’s problems and improve the delivery efficacy of the dry powder inhaler formulation, which is different from applicant’s inventive concept. Staniforth and applicant have different inventive concepts with technical problems to be solved. It is not obvious to combine Muhrer 1 with Staniforth to solve the technical problems of this application and the combination does not teach the claimed technical features A-C as described in the remarks. Applicant further argued that present method uses room temperature, contains no additives, requires a feed rate of 0.5 g/min, requires a micronization pressure of 8-10 bar, processes a blend of drugs having claimed particle sizes and mass ratio, and aims to address a problem of the low deposition rate of glycopyrrolate and the low codeposition rate of the combination of drugs in an inhalation aerosol.
Arguments against Staniforth are not persuasive because Office’s reason for combining and modifying prior art references does not have to be the same as applicant’s reason, in order to arrive at the claimed invention. Applicant’s technical problem and its solution and inventive concept are not claimed limitations and therefore do not have to be addressed in the rejection. It would have been obvious to combine Staniforth with Muhrer 1 for reasons explained in the rejection. Technical features A-C are obvious over the combination of cited references, and not only Staniforth and Muhrer 1. Arguments that present method uses room temperature and contains no additives are not persuasive because these are not claimed limitations. Argument against the feed rate is not persuasive because the feed rate of 0.5 g/min was found obvious because Staniforth provides motivation to optimize the feed rate because the feed rate was recognized as a result effective variable and the skilled artisan would have known to increase it or decrease it depending on the desired particle size of final product. Argument against micronization pressure is not persuasive because claimed range overlaps with prior art pressure range. The combination of references also teaches processing a blend of drugs having a range of particle sizes that overlaps with claimed particle sizes and mass ratio. Arguments related to the aim to address a problem of the low deposition rate of glycopyrrolate and the low codeposition rate of the combination of drugs in an inhalation aerosol is not persuasive because the aim is not a claimed limitation and prior art does not have to have the same aim as applicant to render the claimed invention obvious.
On pages 11-12, applicant argued that Ruecroft does not teach the technical features A-C. Ruecroft’s inventive concept and solution to technical problem is different from applicant’s inventive concept and solution to technical problem. It is not obvious to combine Ruecroft and Muhrer 1 to solve the technical problem of this application and even if the two can be combined their combination does not teach technical features A-C.
Arguments against Ruecroft are not persuasive because Office’s reasons for combining and modifying references does not have to be the same as applicant’s in order to arrive at the claimed invention. The inventive concept of a prior art references does not have to be same as applicant’s for an obviousness rejection to be proper. Applicant’s inventive concept and the solution to its technical problem are not a claimed limitation and the rejection does not have to address these. The claimed technical features are obvious over the combination of cited references and not only Ruecroft and Muhrer 1. One of skill in the art would have been motivated to combined the references and modify Muhrer 1 over Ruecroft for reasons described in the rejection.
On pages 12-14, applicant argued that Ruecroft 1 is concerned with an inventive concept and a solution to a technical problem that are different from applicant’s inventive concept and a solution to a technical problem. It would not be obvious to combine Muhrer 1 with Ruecroft 1 to solve the technical problem of this application. The mass ratio range in Ruecroft 1 is 8:1 to 1:12, which is not 1:1-1:5 as claimed. Experimental results in Examples 2-3 in this application provide results that show mass ratios outside the claimed range result in a higher deposition rate of the effective part of glycopyrronium bromide in the inhalation aerosol. Even if Ruecroft 1 can be combined with Muhrer 1, neither teaches the technical feature A of this application.
Arguments against Ruecroft 1 are not persuasive because Office’s reason for combining and modifying prior art references does not have to be the same as applicant’s for an obviousness rejection to be proper. Applicant’s inventive concept and the solution to solve its technical problem are not claimed limitations and are not required to be addressed in the rejection. Prior art references’ inventive concept and the solution for a technical problem does not have to be the same as applicant’s for a proper obviousness rejection. The claimed range of mass ratios is obvious because it overlaps with the prior art range, as calculated, because it has been held that a prima facie case of obviousness exits where a prior art and claimed ranges overlap. Data in Examples 2 and 3 were considered, however the data are not sufficient to show that the claimed range of weight ratios is critical. The examples show FPF results for the two drugs when in mass ratios of 5:1, 1:1, and 1:5. Only the 5:1 ratio is outside the claimed range and it is unknown if the FPF values are statistically different from results obtained for the 1:1 mass ratio. The applicant did not provide any data outside the range on the 1:5 end. Per MPEP 716.02(d) “To establish unexpected results over a claimed range, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range. In re Hill, 284 F.2d 955, 128 USPQ 197 (CCPA 1960).”. The results have to of statistical significance. The rejection is over a combination of cited references and not only Muhrer 1 and Reucroft 1. The skilled artisan would have been motivated to combine the teachings of Muhrer 1 and Reucroft 1 for reasons described in the rejection.
On pages 14-15 applicant traversed Office’s reason for using coarse, fine, or a mixture of coarse and fine drug particles during micronization because the motivation for improving the micronization of drug particles in Muhrer 2 and Staniforth is completely different from that in this application, so those skilled in the art would have no motivation to combined Muhrer 1, Muhrer 2, and Staniforth. Muhrer 2 and Staniforth teach the micronization of single particle size range, either coarse or fine, and no mention of the simultaneous micronization of drug particles of two different sizes. Applicant referred to Examples 2 and 3 to show that the deposition rate is excellent when the combination of fine and coarse particles is micronized.
Applicant’s argument is not persuasive because Office’s reason to combine and modify prior art references does not have be the same as applicant’s in order to arrive the claimed invention. One of skill would have been motivated to combined said references for reason described in the office action. Micronizing a combination of fine and coarse drug particles would have been obvious because micronizing fine drug particles and micronizing coarse drug particles for the same reason, i.e. to obtain drug particles suitable for inhalation, was known in the art, and it would have been obvious to have combined the two particle sizes and micronized them together to make a composition of drug particles used for the same purpose. The specification was reviewed, and there is no evidence that claimed combinations of fine and coarse particles would have been critical. Examples 2 and 3 were reviewed and they don’t provide comparative data for fine particles only and coarse particles only for the skill artisan to be able to determine whether or not the combination of the two is critical.
On pages 15-16, applicant traversed Office’s obviousness statement of the flow rate because the motivation for improving the micronization of Staniforth drug particles is completely different from that of this application, so there would be no motivation to combined Staniforth with Muhrer 1. The flow rate was limited to 0.5 g/min.
Arguments are not persuasive because Office’s reasons for combining and modifying prior art references do not have to be the same as applicant’s in order to arrive at the claimed invention. Motivation to combine is described in the rejection. The amended flow rate was found obvious as described in the rejection. Per MPEP 2144.05 “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[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) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.)”.
On page 16, applicant provided clarification that when combining existing technical documents, those skilled in the art do not possess creativity. When considering whether prior art provides a teaching or technical enlightenment, they will comprehensively evaluate the inventive concept of that that prior art, i.e. the technical problem to be solved by the improvement scheme, and the technical effects it achieves, rather than forcibly combining technical elements scattered in existing technical documents with the closest prior art. Applicant’s objection to the references is raised based on considering whether the motivation for improvement is the overall existing technical documents combined is consistent with this application and whether there are obstacles to combining it with the closest prior art document, rather than forcibly comparing unrelated technical elements in the existing technical documents to be combined with this application. The applicant hopes for the examiner to examine the technical solution of the amended claims, the technical solution can be considered as a whole, rather than simply splitting its technical elements and only considering whether they have appeared in the existing technical documents to be combined.
Applicant’s clarification was considered, however inventive concept and solving a technical problem are not criteria for determining if the claims meet the 35 USC § 103 statue. Present obviousness rejection identified Muhrer 1 as the primary reference and the rejection provides a detailed explanation as to why it would have been obvious to modify Muhrer 1 by the secondary references in order to arrive at the claimed invention, consistent with MPEP 2141.
On pages 16-17 applicant provided a summary where applicant stated that the inventive concepts in the cited references are completely different from that of this application and based on the problem to be solved in this application, it is not obvious for those skilled in the art to combine the cited references. Even if the references can be combined, the combination cannot obtain the overall technical solution of the amended claim 1. The amended claim 1, which contains the distinctive technical features A-C, is not obvious over the prior art. Applicant described advantages achieved by the claimed invention.
Arguments are not persuasive prior art’s inventive concept and solution for a technical problem do not have to be the same as applicant’s for an obviousness rejection to be proper. The technical solution is not a claimed limitation, thus it is irrelevant that the prior art does not teach applicant’s technical solution. All claimed limitations are obvious and there is motivation to combine the references as described in the rejection. The advantages observed by the applicant would have been present in the prior art because the prior art teaches applicant’s method as described in the rejection. Dependent claims are not patentable for reasons described in the rejection.
On pages 17-19, applicant traverse the rejection of claim 10 because the technical solution and inventive concept in Snape is different from applicant’s technical solution and inventive concept. It is not obvious to combined Snape with Muhrer 1 in order to solve the technical problem addressed by present application, and the additional technical feature of claim 10 is not obtainable in an obvious manner.
Applicant’s argument against Snape is not persuasive because prior art is not required to have the same inventive concept and technical solution as applicant in order for an obviousness rejection to be proper. Applicant’s technical problem and solution and inventive concept are not a claimed limitation, thus the rejection does not have to address these.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/ALMA PIPIC/
Primary Examiner, Art Unit 1617