DETAILED ACTION
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 13-18 are withdrawn.
Claims 1-12 are pending and represent all claims currently under consideration.
Response to Amendment
The amendment filed 10/23/2025 has been entered.
Claims 1, 8, and 11 were amended. No new material was added.
Applicant’s amendments have overcome the objections to the specification and claims, and the rejections of claims 1, 8, and 12 under 35 U.S.C. 112(b).
The rejection of claims 5-6 and 11 under 35 U.S.C. 112(b) has been maintained.
The rejection of claims 1-12 under 35 U.S.C. 103 has been modified to address the amendments and maintained.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claims 1-12 are considered to have an effective filing date of 04/17/2019.
Response to Arguments
Applicant's arguments filed 10/23/2025 have been fully considered but they are not persuasive.
Applicant states the rejection of claim 11 is moot with respect to the recitation of “excessively large” due to the amendment (Remarks, pages 7-8, item 1). This argument is not persuasive, because this issue was not addressed.
Applicant states that claims 5-6 do not lack antecedent basis, because the terms are inherent characteristics of other recited elements (Remarks, page 8, item 2). This argument is not persuasive, because it is not clear that “the dry matter content of the spray composition” is referring to “an active ingredient and optionally one or more excipients” as stated in the Remarks, because there is no statement limiting these components as “dry matter” in the claims. Therefore, the recitation of “the proportion of the active ingredient in the dry matter content” is also unclear.
Applicant argues that no person skilled in the art would look to the cited references to create the claimed invention because they do not address the problems that the claimed invention solves (Remarks, page 10, 2nd paragraph). This argument is not persuasive, because a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992). In this case, the cited references are both in the field of preparing granulate pharmaceutical compositions as diabetes treatments (specifically metformin in the case of Delaet), while the instant invention is in the field of preparing granulate pharmaceutical compositions comprising metformin, which is a commonly known diabetes medication. Therefore, the prior art references are in the same field of the inventor’s endeavor.
Applicant argues that the examples contained in the specification demonstrate superior flow properties and stability can be achieved and maintained, and that Galli does not teach or suggest a high-flowability granulate from a low-flowability active ingredient such as metformin (Remarks, pages 10-12). This argument is not persuasive, because the assertion that the flow properties and stability are superior over the prior art is not supported by evidence. An affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. See MPEP 716.02(e). Further, Galli teaches flow characteristics may be varied to accommodate different active ingredients (Galli, page 6, paragraph 0072) and specifically states the methods aim to form stabilized granulations (Galli, abstract).
Applicant argues that Galli does not teach or suggest growing particles with a liquid spray composition, thereby producing improved flow properties and stability (Remarks, pages 12-13). This argument is not persuasive, because there is no limitation in the claims that is directed to growing particles. Further, Galli teaches the dispersion is discharged through a spray homogenizer (i.e., the dispersion is a spray composition; Galli, claim 1), as stated in the rejection below.
Applicant states that the high-pressure spray homogenizer of Galli cannot be used for granulation (Remarks, pages 14-15). This argument is not persuasive, because as previously stated, Galli defines spray drying as spraying an active pharmaceutical ingredient dispersed in a liquid carrier into a hot gas to produce granules (Galli, page 5, paragraph 0063). Galli further states suitable granulators include spray dryers (Galli, page 2, paragraph 0013).
Applicant states that nothing in Galli supports the view that the cooling system would constitute the claimed process space (Remarks, page 15). This argument is not persuasive, because as stated in the rejection below, Galli teaches the spray homogenizer includes a cooling system for processing (i.e., a process space) of the solid particle dispersion (i.e., step "b" as claimed; Galli, claim 5).
Applicant states that Galli describes the spray dryer as unrelated to the cooling system, and further states the spray dryer of Galli is not suitable to allow guiding solid particles back past sprayed droplets in the process space with the aid of a process gas jet (Remarks, pages 15-17). This argument is not persuasive, because Galli states the cooling system is for controlling the process temperature of the spray homogenizer (Galli, page 4, paragraph 0057), and further teaches the spray jet homogenizer can be used for reprocessing as part of a recycling loop (i.e., step "d" as claimed; Galli, page 5, paragraph 0060). Reprocessing suggests the particles are being recycled back into the process space.
Applicant states that the particle agglomeration of Galli does not suggest that the high-pressure spray homogenizer could lead to larger particles compared to the starting material (Remarks, pages 18-19). This argument is not persuasive, because one of ordinary skill in the art would recognize that agglomeration of particles as taught by Galli would lead to larger particles as stated in the claim.
Applicant argues that the nanoparticles of Galli have a median particle size and d90 of less than about 1 and 5 micrometers, respectively, while the applicant’s process has a preferred range for the median particle size of 100 to 600 micrometers (Remarks, pages 19-20). This argument is not persuasive, because as stated previously, Galli defines a coarse dispersion as particles ranging in size from 1-500 micrometers (Galli, page 3, paragraph 0045), which overlaps the claimed range of 100-600 micrometers, and teaches smaller removed particles. Delaet teaches a metformin hydrochloride containing tablet with a mean particle size (d50) of 190 micrometers, which lies within the claimed range, after removal using a mesh screen (Delaet, page 13, paragraph 0159).
Applicant states that no skilled person in the art would seek to modify Galli according to Delaet without impermissibly rendering the metformin unsuitable for its intended purpose or changing Delaet’s principle of operation, because rapid dissolution is unwanted (Remarks, pages 20-21). Applicant states that Galli teaches a nanoparticular form of antidiabetic drugs, and states that particle size reduction can lead to an increased rate of dissolution (Remarks, page 20). This argument is not persuasive, because the rejection is not based on modifying the formulation of Delaet to increase dissolution, nor is it based on providing metformin in nanoparticle form for extended release. Rather, the rejection is based on modifying the teachings of Galli to have included metformin hydrochloride as the specific antidiabetic agent, because Galli does not teach a specific chemical, while Delaet teaches Metformin is a first-line choice of therapy for type II diabetes (Delaet, page 2, paragraph 0014).
Modified/Maintained 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 5-6 and 11 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.
Claims 5-6 recite the limitation "the dry matter content". There is insufficient antecedent basis for this limitation in the claim.
Claim 6 recites the limitation "the proportion". There is insufficient antecedent basis for this limitation in the claim.
Claim 11 recites the term “excessively large”, which is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Modified/Maintained 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 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 1-12 are rejected under 35 U.S.C. 103 as being unpatentable over Galli (US 20070020197 A1), further in view of Delaet (US 20120009259 A1). The references were cited previously by the Examiner.
Regarding claim 1, Galli teaches the continuous preparation of pharmaceutical granulations comprising an active pharmaceutical ingredient (Galli, page 4, paragraph 0056) comprising forming a dispersion of the active pharmaceutical ingredient in solid particles in the presence of a liquid carrier (i.e., step "a" as claimed; Galli, claim 6) which can be combined with one or more excipients (Galli, page 2, paragraph 0018) and teaches the dispersion is discharged through a spray homogenizer (i.e., the dispersion is a spray composition; Galli, claim 1). Galli further teaches the spray homogenizer includes a cooling system for processing (i.e., a process space) of the solid particle dispersion (i.e., step "b" as claimed; Galli, claim 5), and teaches the suspension enters (i.e., injects into) a spray dryer which drives off the liquid (i.e., step "c" as claimed; Galli, page 5, claim 0061). Galli teaches the spray jet homogenizer can be used for reprocessing as part of a recycling loop (i.e., step "d" as claimed; Galli, page 5, paragraph 0060), defines spray drying as spraying an active pharmaceutical ingredient dispersed in a liquid carrier into a hot gas to produce granules (Galli, page 5, paragraph 0063), and states that particle agglomeration occurs at high temperatures (Galli, page 8, paragraph 0094). Galli further teaches the resulting dry granulation as particles which are fed into a milling operation (i.e., removed from the process space as claimed in step "e"; Galli, page 5, paragraph 0064), and teaches such particles as solid particles (Galli, page 3, paragraph 0046).
Galli does not specifically state the active ingredient comprises metformin or a salt of metformin as claimed, but does teach the active ingredient can be an antidiabetic agent (Galli, page 6, paragraph 0073). Delaet teaches a pharmaceutical composition for the treatment of diabetes (Delaet, abstract) which is a granule comprising metformin hydrochloride (i.e., an acid addition salt of metformin; Delaet, claim 7).
Galli and Delaet are considered to be analogous to the claimed invention, because both are in the same field of preparing granulate pharmaceutical compositions as diabetes treatments. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Galli to have included metformin hydrochloride as the specific antidiabetic agent, because Galli does not teach a specific chemical, while Delaet teaches Metformin is a first-line choice of therapy for type II diabetes (Delaet, page 2, paragraph 0014).
Regarding claim 2, Galli and Delaet together teach all the elements of the current invention as applied to claim 1. As above, Galli does not specifically state the active ingredient comprises metformin hydrochloride as claimed, but does teach the active ingredient can be an antidiabetic agent (Galli, page 6, paragraph 0073), while Delaet teaches a pharmaceutical composition for the treatment of diabetes (Delaet, abstract) which is a granule comprising metformin hydrochloride (Delaet, claim 7). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Galli to have included metformin hydrochloride as the specific antidiabetic agent, because Galli does not teach a specific chemical, while Delaet teaches Metformin is a first-line choice of therapy for type II diabetes (Delaet, page 2, paragraph 0014).
Regarding claim 3, Galli and Delaet together teach all the elements of the current invention as applied to claim 1. Galli teaches the liquid carrier can be water (Galli, page 4, paragraph 0057).
Regarding claim 4, Galli and Delaet together teach all the elements of the current invention as applied to claim 1. Galli teaches formulations may include binders (Galli, page 5, paragraph 0067).
Regarding claim 5, Galli and Delaet together teach all the elements of the current invention as applied to claim 1. Galli teaches the solid particles (i.e., dry matter) in the liquid carrier in 30% w/w or more (Galli, claim 3), which lies within the claimed range.
Regarding claim 6, Galli and Delaet together teach all the elements of the current invention as applied to claim 5. Galli teaches the active pharmaceutical ingredient comprises from about 5-95% w/w of the dry granulation (Galli, page 5, paragraph 0062), which overlaps the claimed range of at least 70% by weight. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. See MPEP §2144.05(I).
Regarding claim 7, Galli and Delaet together teach all the elements of the current invention as applied to claim 1. Galli teaches the dispersion supplied into the spray homogenizer comprises solid particles is suspended in the liquid phase (i.e., the spray composition is a suspension; Galli, page 4, paragraph 0057).
Regarding claim 8, Galli and Delaet together teach all the elements of the current invention as applied to claim 1. Galli teaches the dispersion of particles is discharged through a spray homogenizer (i.e., sprayed; Galli, claim 1), then enters a spray dryer (i.e., a processing space) which drives off (i.e., evaporates) the liquid (Galli, page 5, paragraph 0061). Galli does not teach any other substance entering the spray dryer prior to this step, so it would be reasonable to expect that the spray dryer is otherwise empty.
Regarding claim 9, Galli and Delaet together teach all the elements of the current invention as applied to claim 1. Galli teaches the number of cycles is related to the resulting particle size distribution (Galli, page 8, paragraph 0089) and the particle size is measured using laser diffraction (Galli, page 3, paragraph 0043). Galli further teaches optional reprocessing recycling of the particle suspension through the spray homogenizer (Galli, page 5, paragraph 0060), suggesting it would be obvious to reprocess if a specified size is not reached.
Regarding claim 10, Galli and Delaet together teach all the elements of the current invention as applied to claim 1. Galli teaches recycling of the particle suspension through the spray homogenizer (Galli, page 5, paragraph 0060) and teaches controlling particle size distribution with the number of cycles (i.e., particles which are not of a desired size are reprocessed; Galli, page 8, paragraph 0089).
Regarding claim 11, Galli and Delaet together teach all the elements of the current invention as applied to claim 1. Galli teaches the number of cycles is related to the resulting particle size distribution (Galli, page 8, paragraph 0089) and the particle size is measured using laser diffraction (Galli, page 3, paragraph 0043). Galli further teaches the spray homogenizer is for comminution (Gail, page 2, paragraph 0013) and teaches optional reprocessing recycling of the particle suspension through the spray homogenizer (Galli, page 5, paragraph 0060), suggesting it would be obvious to reprocess if a specified size is not reached after the first comminution.
Regarding claim 12, Galli and Delaet together teach all the elements of the current invention as applied to claim 1. Galli defines a coarse dispersion as particles ranging in size from 1-500 micrometers (Galli, page 3, paragraph 0045), which overlaps the claimed range of 100-600 micrometers, but teaches smaller removed particles. Delaet teaches a metformin hydrochloride containing tablet with a mean particle size (d50) of 190 micrometers, which lies within the claimed range, after removal using a mesh screen (Delaet, page 13, paragraph 0159). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Galli to have included metformin hydrochloride as the specific antidiabetic agent, because Galli does not teach a specific chemical, while Delaet teaches Metformin is a first-line choice of therapy for type II diabetes (Delaet, page 2, paragraph 0014), which would be reasonably expected to result in particles of the specific size taught by Delaet.
Conclusion
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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/C.P.J./Examiner, Art Unit 1613
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613