DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis 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.
Status of the Claims
The claims filed 09/26/2024 are under consideration.
Claims 1-15 are pending.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. Rejections not reiterated herein have been withdrawn.
Claim Objections
Claim 1 is objected to because of the following informalities: Claim 1 includes the recitation of “MS(hydroxyalkyl)” in line 5. The meaning of this term, found in the specification at pg. 6:4-14 – molar substitution (MS) of hydroxyalkyl groups which are bound by an ether bond per mole of anhydroglucose unit - should be recited in the claims at the first instance of usage for clarity. Appropriate correction is required.
Claim 6 is objected to because of the following informalities: Claim 6 includes the recitation of “DS(methyl)” in line 2. The meaning of this term, found in the specification at pg. 6:4-5 – degree of substitution (DS) for methyl substituents - should be recited in the claims at the first instance of usage for clarity. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
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 1-15 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 pre-AIA the applicant regards as the invention.
1. Claim 1 includes the phrase “the ether substituents” in line 3. There does not appear to be clear antecedent basis for “the ether substituents.”
This phrase may refer to “hydroxyalkyl” and/or “methyl” of line 2. However, it is not clear if the phrase was intended to refer to the hydroxyalkyl groups, the methyl groups or some other ether groups of the “hydroxyalkyl methylcellulose.”
For examination the phrase is interpreted to refer to hydroxyalkyl or methyl groups of the hydroxyalkyl methylcellulose.
2. The limitation of wherein the concentration of hydroxyalkyl methylcellulose is 0.1-10% by dry weight of the active ingredient is unclear. Percent is part (numerator) of a total (denominator) multiplied by 100%. However, it is not clear what the “total” is in calculating the recited percent concentration. This may mean the active agent is the total. However, if the denominator is only one part of the whole, i.e., only the weight of the active agent is the denominator, then the value is a weight ratio of the two components and the percent by dry weight is confusing. Alternatively, this may mean the dry weight of the hydroxyalkyl methylcellulose and the active agent is the total. The further limitations of claims 2 and 3 are also unclear for the same reason. There does not appear to be an example of this calculation in the specification. The skilled artisan cannot determine how the recited concentration is calculated.
Dependent claims do not clarify these issues.
Clarification is required.
Claim 7 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 pre-AIA the applicant regards as the invention.
Claim 7 includes the limitation of wherein the hydroxyalkyl methylcellulose constitutes at least 50% by weight of a polymeric matrix in which particles of the active ingredient are embedded.
1) It is not clear how the concentration of hydroxyalkyl methylcellulose can be 0.1-10% by dry weight of the active ingredient as required in claim 1, in combination with wherein the hydroxyalkyl methylcellulose can be at least 50% by weight of a polymeric matrix in which particles of the active ingredient are embedded as required by claim 7. The limitaion appears to require the matrix containing both hydroxyalkyl methylcellulose and active ingredient, which matrix is at least 50% by mass hydroxyalkyl cellulose. This means the mass of hydroxyalkyl cellulose has to be close to, e.g., 50%, or greater than, the dry weight of the active ingredient in the polymeric matrix. However, the limitation in claim 1 does not allow the concentration of hydroxyalkyl methylcellulose to be greater than 10% of the dry weight of the active ingredient in the composition. The limitations of claim 7 do not appear to be consistent with the limitations of claim 1 from which it depends.
2) there is a lack of antecedent basis for a polymeric matrix in which particles of the active ingredient are embedded. It is not clear if claim 7 further comprises a polymeric matrix and particles of active agent embedded in the polymeric matrix.
Clarification is required.
Claim 9 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 pre-AIA the applicant regards as the invention.
There is insufficient antecedent basis for “the concentration of the surfactant” in claim 9 because claim 1 does not refer to a surfactant or a concentration thereof.
Clarification is required.
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 of this title, 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.
Claims 1-9, 12-13, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Brackhagen, US 20150057358 A1 in view of Hsiao, US 5885616.
Brackhagen teaches sustained release dosage forms comprising compositions comprising a matrix including an active ingredient blended with a polymer (Brackhagen, e.g., Abstract and claims), the polymer being a cellulose ether having methyl groups, hydroxyalkyl groups, and optionally alkyl groups different from methyl as substituents (Brackhagen, e.g., Abstract). Brackhagen teaches the composition for oral delivery (Brackhagen, e.g., 0049). Brackhagen teaches compositions comprising a polymeric matrix wherein at least a portion of the polymeric matrix is formed by the cellulose ether (Brackhagen, e.g., 0050). The cellulose ether has an MS (hydroxyalkyl) of 0.05 to 1.00, and hydroxyl groups of anhydroglucose units are substituted with methyl groups such that [s23/s26−0.2*MS(hydroxyalkyl)] is 0.31 or less, wherein s23 is the molar fraction of anhydroglucose units wherein only the two hydroxyl groups in the 2- and 3-positions of the anhydroglucose unit are substituted with a methyl group and wherein s26 is the molar fraction of anhydroglucose units wherein only the two hydroxyl groups in the 2- and 6-positions of the anhydroglucose unit are substituted with a methyl group. See Brackhagen, e.g., 0016-0021.
The claimed range for [s23/s26−0.2*MS(hydroxyalkyl)] is entirely within the range of 0.31 or less in Brackhagen. Brackhagen also teaches the range of 0.30 or less (Brackhagen, e.g., 0016).
Brackhagen teaches the amount of cellulose ether generally is at least 5 percent, e.g., at least 10 percent, based on the total weight of the dosage form (Brackhagen, e.g., 0051). Brackhagen teaches the amount of active ingredient generally is at least 0.5%, at least 10%, and generally up to 75% based on the total weight of the dosage form (Brackhagen, e.g., 0052).
Brackhagen teaches the particular cellulose ethers enables controlled release at a reduced weight of the polymeric matrix, thereby achieving controlled release dosage forms which are smaller and easier to ingest (Brackhagen, e.g., 0050).
Regarding wherein the concentration of hydroxyalkyl methylcellulose is 0.1-10% by dry weight of the active ingredient:
Brackhagen does not expressly teach the composition wherein the concentration of hydroxyalkyl methylcellulose is 0.1-10% by dry weight of the active ingredient as recited in claim 1 or the amounts recited by claims 2-3. It is noted that this limitation refers to a composition but does not limit further amounts of hydroxyalkyl methylcellulose present in a unit dosage form containing the composition of claim 1.
Based on Brackhagen, the amount of hydroxyalkyl methylcellulose is a result effective parameter the skilled artisan would have routinely optimized to achieve a desired period of release. The skilled artisan would have optimized the amount of hydroxyalkyl methylcellulose depending on the desired release time frame, e.g., between 8-24 hours (Brackhagen, e.g., 0049), the amount and nature of the drug, e.g., solubility, and the amount(s) and nature of additional excipient(s) present in the composition. Brackhagen clearly teaches the cellulose ether is an extended-release agent when combined with active ingredients in a dosage form (Brackhagen, e.g., 0006). Because the cellulose ether is an extended-release agent, the skilled artisan understood the relative amount of hydroxyalkyl methylcellulose and active compound in the matrix was a ratio to be optimized to achieve a desired extended-release time frame. Brackhagen teaches the amount of hydroxyalkyl methylcellulose is generally at least about 5% based on the weight of the dosage form (Brackhagen, e.g., 0051) and the amount of hydroxyalkyl methylcellulose may be reduced to achieve a smaller and easier to ingest dosage form (Brackhagen, e.g., 0050).
Further, sustained release compositions comprising an amount of hydroxypropyl methylcellulose relative to the active agent in a range overlapping with the claimed amount was known and used in prior art dosage forms. In this regard, Hsiao teaches drug containing compositions for pharmaceutical use in formulating unit dosage forms, the composition comprising drug ranging from 70-100%, binding agent such as hydroxypropyl methylcellulose in an amount ranging from 0-30%, and a surfactant in an amount ranging from 0-10% by weight. See Hsiao, e.g., c7:5-35, table 1. Here, Hsiao teaches exemplary compositions comprising 90% drug, 9% binding agent such as hydroxypropyl methylcellulose, and 1% surfactant. This is about 10% HPMC (90/10x100%) by weight of the drug. Clearly, the amount of HPMC may vary over the range of form 0-30% for a given drug concentration, and Hsiao teaches the ratio between binding agent, e.g., HPMC, and drug may vary widely with a reasonable expectation of success.
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); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05. The claimed range is similar to the amount suggested by Brackhagen, e.g., generally at least 5% by weight of the composition and within the range by weight of the active agent known from the prior art as evident from Hsiao.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the presently claimed invention to optimize the amount hydroxyalkyl methylcellulose, e.g., hydroxypropyl methylcellulose by weight of the active agent within the range suggested by the prior art with a reasonable expectation of success. The skilled artisan would have been motivated to optimize the amount of hydroxyalkyl methylcellulose based on the weight of the composition, including the amount of the active agent, to achieve a desired extended-release time frame depending on the desired release time frame, the dose and nature of the drug, e.g., solubility, and the amount and nature of additional excipients present in the composition. Brackhagen provides a suggestion which would have prompted the skilled artisan to minimize the amount of hydroxyalkyl methylcellulose since this would make unit dosage forms smaller and easier to ingest while maintaining extended release. The skilled artisan would have had a reasonable expectation of success since Hsiao provides a workable range overlapping with the claimed range in which similar hydroxypropyl methylcellulose polymers were useful to prepare pharmaceutical compositions useful in unit dosage forms.
Applicable to claims 2-3: the claimed range of 0.2-5% (claim 2) and 1.5% (claim 3) for hydroxyalkyl methylcellulose by weight of active ingredient is suggested by the combined teachings of Brackhagen and Hsiao. Hsiao, e.g., c7:5-35, table 1. The amount of hydroxyalkyl methylcellulose may be reduced to achieve a smaller and easier to ingest dosage form (Brackhagen, e.g., 0050).
Applicable to claim 4: Brackhagen also teaches the range of 0.27 or less (Brackhagen, e.g., 0016).
Applicable to claim 5: Brackhagen also teaches the range of 0.30 or less (Brackhagen, e.g., 0016) and wherein the hydroxyalkyl methyl cellulose is hydroxyethyl methylcellulose (Brackhagen, e.g., 0015).
Applicable to claim 6: Brackhagen teaches DS(methyl) of from 1.2 to 2.2 (Brackhagen, e.g., 0020).
Applicable to claim 7: Brackhagen teaches the cellulose ether may form from 50 to 100 percent of the weight of the polymeric matrix comprising the active agent and polymer blend (Brackhagen, e.g., 0051).
Applicable to claims 8-9: Brackhagen teaches wherein the composition further comprises a surfactant (Brackhagen, e.g., 0052). Hsiao teaches the drug containing composition further comprising a surfactant in an amount ranging from 0-10% by weight to improve properties of the pharmaceutical composition or texture (Hsiao, e.g., c7:5-35, table 1). 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); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05.
Applicable to claim 12: Dry powdered mixtures are compressed to form tablets (Brackhagen, e.g., 0074).
Applicable to claim 13: Brackhagen teaches unit dosage forms, e.g., tablets (Brackhagen, e.g., 0050).
Applicable to claim 15: Brackhagen teaches wherein the active is paracetamol, i.e., acetaminophen (Brackhagen, e.g., 0052 and 0074).
Accordingly, the subject matter of claims 1-9, 12-13, and would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Claim(s) 7 and 12-15 are rejected under 35 U.S.C. 103 as being unpatentable over Brackhagen, US 20150057358 A1 in view of Hsiao, US 5885616 as applied to claims 1-9, 12-13, and 15 above, and further in view of Hou, US 20110104272.
The combined teachings of Brackhagen and Hsiao teach compositions according to claim 1, in the form of a unit dosage form such as a tablet as enumerated above, but do not expressly teach the unit dosage form comprising 500-1000 mg of the active ingredient.
However, it was known to produce unit dosage forms comprising amounts of active ingredients in the claimed range before the effective filing date of the presently claimed invention. For example, Hou teaches extended-release dosage forms for acetaminophen (Hou, e.g., abstract), wherein the extended-release dosage form comprises particles of acetaminophen admixed with a polymer as per instant claim 7 (Hou, e.g., 0024 and 0108), wherein the dosage form is a unit dosage form comprising an amount of drug (Hou, e.g., 0177), and wherein the amount of drug, e.g., acetaminophen, is present in an amount ranging from 325 mg to 2000 mg (Hou, e.g., 0109). Acetaminophen may be formulated in the dosage form in a variety of values within the claimed range, e.g., 500 mg, 525 mg, 700 mg, etc. (Hou, e.g., 0044) and claim 4. 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); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05. Hou teaches compositions in the form of a dry powder may be compressed to arrive at a unit dosage form such as a tablet (Hou, e.g., 0150-0153).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the presently claimed invention to optimize the amount of drug in a composition taught by Brackhagen and Hsiao within the range of from 325-2000 mg as known from Hou with a reasonable expectation of success. The skilled artisan would have been motivated to optimize the amount of drug in the range suggested by Hou with a reasonable expectation of success since Hou teaches drug amounts in this range are reasonable for a single dosage unit, and effective for sustained release over time frames similar to those desired by Brackhagen.
Accordingly, the subject matter of claims 7 and 12-15 would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Claim(s) 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over Brackhagen, US 20150057358 A1 in view of Hsiao, US 5885616 as applied to claims 1-9, 12-13, and 15 above, and further in view of Sinnreich, US 4996058.
The combined teachings of Brackhagen and Hsiao teach compositions according to claim 1, in the form of a unit dosage form such as a tablet as enumerated above, but do not expressly teach the composition further comprising an additive capable of reacting with gastric fluid to generate a gas.
Sinnreich teaches modifying dosage forms with a component that expands on contact with a body fluid, e.g., gastric juice such as sodium hydrogen carbonate (Sinnreich, e.g., Abstract and ¶ spanning c2-c3). This enables retention of the dosage form in the stomach increasing the duration of time available for extended release in the stomach and the gastrointestinal tract. Alkali metal carbonates and alkaline metal earth carbonates are found in Sinnreich at c3:26-37.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the presently claimed invention to modify a sustained release composition known from Brackhagen and Hsiao by incorporating an alkali metal carbonates and/or alkaline metal earth carbonate to improve the retention time of dosage forms containing the composition in the stomach in the same way suggested by Sinnreich. The skilled artisan would have been motivated to make this modification to increase the amount of time available for extended release, thereby increasing the therapeutic window for a single administration. The skilled artisan would have had a reasonable expectation of success since Sinnreich’s carbonates enable release over the time frames desired by Brackhagen.
Accordingly, the subject matter of claims 10-11 would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claim(s) 1-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim(s) 1-15 of US 9616036 in view of Hsiao, US 5885616, Hou, US 20110104272, and Sinnreich, US 4996058.
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The claims of the reference patent are directed to a sustained release dosage form comprising at least one active ingredient blended with a polymeric matrix, wherein at least a portion of the polymeric matrix is formed by at least one cellulose ether having an onset dissolution temperature of at least 40° C., having anhydroglucose units joined by 1-4 linkages and having methyl groups, hydroxyalkyl groups, and optionally alkyl groups being different from methyl as substituents such that said at least one cellulose ether has an MS (hydroxyalkyl) of 0.05 to 1.00, and hydroxyl groups of anhydroglucose units are substituted with methyl groups such that s23/s26−0.2*MS(hydroxyalkyl) is 0.31 or less, wherein s23 is the molar fraction of anhydroglucose units wherein only the two hydroxyl groups in the 2- and 3-positions of the anhydroglucose unit are substituted with a methyl group and wherein s26 is the molar fraction of anhydroglucose units wherein only the two hydroxyl groups in the 2- and 6-positions of the anhydroglucose unit are substituted with a methyl group, and wherein said at least one cellulose ether has an onset dissolution temperature of at least 40° C., measured at a concentration of 2 weight percent in water and wherein the amount of said at least one cellulose ether is at least 10 percent, based on the total weight of the dosage form (Claim 1). DS(methyl) and MS(hydroxyl) are overlapping or within the claimed ranges (claims 5-6 and 7).
The reference patent claims do not expressly teach the concentration of hydroxyalkyl methylcellulose is 0.1-10% by dry weight of the active ingredient. The reference patent claims do not expressly teach the composition further comprising a surfactant in the claimed amount.
However, the teachings of Hsiao above cure these deficiencies.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the presently claimed invention to modify a sustained release dosage form as claimed by the reference patent by optimizing the amount of hydroxyalkyl methylcellulose relative to the amount of drug, and an effective amount of surfactant as suggested in Hsiao with a reasonable expectation of success. The skilled artisan would have been motivated to optimize the amounts of ingredients within the ranges suggested by Hsiao to enable release of therapeutically effective amounts of drug over an extended time frame and in a controlled manner.
The reference patent claims do not expressly teach a unit dosage form. However, Hou teaches unit dosage forms, e.g., single units (Hou, e.g., 0177), e.g., tablets comprising extended release (Hou, e.g., 0039), wherein the dosage form comprises 325-2000 mg of drug, e.g., acetaminophen (Hou, e.g., 0109). Hou teaches compositions in the form of a dry powder may be compressed to arrive at a unit dosage form such as a tablet (Hou, e.g., 0150-0153).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the presently claimed invention to modify a dosage form suggested by the reference patent claims and a Hsiao by formulating 325-2000 mg of drug, e.g., acetaminophen, in for extended release in a single dosage form such as a tablet as suggested by Hou. Since Hou teaches the amount of drug is limited in a single dosage form the skilled artisan would have been motivated to optimize the amount of drug in a single tablet within the range suggested by Hou for sustained release with a reasonable expectation of success.
The combined teachings of the reference patent claims, Hsiao and Hou do not expressly teach the dosage form comprising an additive which reacts with gastric fluid or hydroxyethyl methylcellulose.
However, Sinnreich cures these deficiencies.
Sinnreich teaches modifying dosage forms with a component that expands on contact with a body fluid, e.g., gastric juice such as sodium hydrogen carbonate (Sinnreich, e.g., Abstract and ¶ spanning c2-c3). This enables retention of the dosage form in the stomach increasing the duration of time available for extended release in the stomach and the gastrointestinal tract. Alkali metal carbonates and alkaline metal earth carbonates are found in Sinnreich at c3:26-37. Sinnreich teaches hydroxyethyl methylcellulose and hydroxypropyl methylcellulose were known alternatives since the alkyl group of the hydroxyalkyl methylcellulose is typically an alkyl group containing 1-4 carbon atoms (Sinnreich, e.g., c4:4-11).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the presently claimed invention to modify a sustained release composition known from the reference patent claims, Hsiao and Hou by incorporating an alkali metal carbonates and/or alkaline metal earth carbonate to improve the retention time of dosage forms containing the composition in the stomach in the same way suggested by Sinnreich. The skilled artisan would have been motivated to make this modification to increase the amount of time available for extended release, thereby increasing the therapeutic window for a single administration. The skilled artisan would have had a reasonable expectation of success since Sinnreich’s carbonates enable sustained release as desired by reference patent claims.
Accordingly, the subject matter of claims 1-15 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Claim(s) 1-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim(s) 1-16 of US 18790448 in view of Brackhagen, US 20150057358 A1.
The claims of the reference application are directed to a sustained release composition for oral administration comprising a physiologically active ingredient mixed with a methylcellulose, wherein the methylcellulose has anhydroglucose units joined by 1-4 linkages and wherein hydroxy groups of anhydroglucose units are substituted with methyl groups such that the s23/s26 is more than 0.27, wherein s23 is the molar fraction of anhydroglucose units wherein only the two hydroxy groups in the 2- and 3-positions of the anhydroglucose unit are substituted with methyl groups and wherein s26 is the molar fraction of anhydroglucose units wherein only the two hydroxy groups in the 2- and 6-positions of the anhydroglucose unit are substituted with methyl groups, and wherein the concentration of methylcellulose is from 0.1% to 10% by dry weight of the active ingredient. Further comprising a surfactant is found in claims 8-9. Further comprising an additive reactive with gastric fluid is found in claims 10-11. Unit dosage form, amount of active and named active agents are is found in claims 13-15.
The claims of the reference application do not expressly teach wherein the methylcellulose is a hydroxyalkyl methylcellulose having an MS (hydroxyalkyl) of 0.05 to 1.00, and hydroxyl groups of anhydroglucose units are substituted with methyl groups such that [s23/s26−0.2*MS(hydroxyalkyl)] is 0.30 or less, wherein s23 is the molar fraction of anhydroglucose units wherein only the two hydroxyl groups in the 2- and 3-positions of the anhydroglucose unit are substituted with a methyl group and wherein s26 is the molar fraction of anhydroglucose units wherein only the two hydroxyl groups in the 2- and 6-positions of the anhydroglucose unit are substituted with a methyl group.
However, the teachings of Brackhagen enumerated above cures this deficiency. See Brackhagen, e.g., 0016-0021. Brackhagen teaches hydroxypropyl methylcellulose and/or hydroxyethyl methylcellulose (Brackhagen, e.g., 0015) offer greater sustained release relative to conventional cellulose sustained release agents (Brackhagen, e.g., 0050).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the presently claimed invention to modify a sustained release composition and dosage form claimed by the reference application by incorporating a hydroxyalkyl methylcellulose known from Brackhagen with a reasonable expectation of success. The skilled artisan would have seen this modification as combining two known cellulose ethers each separately known in the art for preparing sustained release compositions to arrive at a third composition useful for the same purpose. Combining art recognized equivalents to achieve predictable results is prima facie obvious. The skilled artisan would have been motivated to optimize the amount of hydroxyalkyl methylcellulose in the range of from 0.1 to 10% as suggested by the claims of the reference application with a reasonable expectation of successfully arriving at a composition capable of sustained release of the active agent incorporated in the composition.
Accordingly, the subject matter of claims 1-15 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Claim(s) 1-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim(s) 1-16 of US 19081897 in view of Brackhagen, US 20150057358 A1, and Hsiao, US 5885616.
The claims of the reference application are directed to a sustained release composition for oral administration comprising a physiologically active ingredient mixed with a methylcellulose, wherein the methylcellulose has anhydroglucose units joined by 1-4 linkages and wherein hydroxy groups of anhydroglucose units are substituted with methyl groups such that the s23/s26 is 0.27 or less, wherein s23 is the molar fraction of anhydroglucose units wherein only the two hydroxy groups in the 2- and 3-positions of the anhydroglucose unit are substituted with methyl groups and wherein s26 is the molar fraction of anhydroglucose units wherein only the two hydroxy groups in the 2- and 6-positions of the anhydroglucose unit are substituted with methyl groups, the composition further comprising a liquid diluent in a weight ratio of liquid diluent to active ingredient in the range of 0:1 to 0.85:1 (claim 1). the concentration of methylcellulose is from 0.1% to 10% by dry weight of the active ingredient. Further comprising a surfactant is found in claims 5-6. Further comprising an additive reactive with gastric fluid is found in claims 7-8. Unit dosage form, amount of active and named active agents are is found in claims 10-11. Solid dosage forms comprising a polymer matrix are found in claims 12-15.
The claims of the reference application do not expressly teach hydroxyalkyl methylcellulose having an MS (hydroxyalkyl) of 0.05 to 1.00, and hydroxyl groups of anhydroglucose units are substituted with methyl groups such that [s23/s26−0.2*MS(hydroxyalkyl)] is 0.30 or less, wherein s23 is the molar fraction of anhydroglucose units wherein only the two hydroxyl groups in the 2- and 3-positions of the anhydroglucose unit are substituted with a methyl group and wherein s26 is the molar fraction of anhydroglucose units wherein only the two hydroxyl groups in the 2- and 6-positions of the anhydroglucose unit are substituted with a methyl group.
However, the teachings of Brackhagen enumerated above cures this deficiency. See Brackhagen, e.g., 0016-0021. Brackhagen teaches hydroxypropyl methylcellulose and/or hydroxyethyl methylcellulose (Brackhagen, e.g., 0015). Brackhagen teaches wherein the hydroxyalkyl methylcellulose makes up at least about 50% of the polymer matrix (Brackhagen, e.g., 0051). Brackhagen teaches hydroxypropyl methylcellulose and/or hydroxyethyl methylcellulose (Brackhagen, e.g., 0015) offer greater sustained release relative to conventional cellulose sustained release agents (Brackhagen, e.g., 0050).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the presently claimed invention to modify a sustained release composition and dosage form claimed by the reference application by incorporating a hydroxyalkyl methylcellulose known from Brackhagen with a reasonable expectation of success. The skilled artisan would have seen this modification as combining two known cellulose ethers each separately known in the art for preparing sustained release compositions to arrive at a third composition useful for the same purpose. The skilled artisan would have been motivated to make this modification for the improved sustained release reported in Brackhagen. Combining art recognized equivalents to achieve predictable results is prima facie obvious. The skilled artisan would have been motivated to optimize the amount of hydroxyalkyl methylcellulose in the range of from 0.1 to 10% as suggested by the claims of the reference application with a reasonable expectation of successfully arriving at a composition capable of sustained release of the active agent incorporated in the composition with sustained release.
The claims of the reference application and Brackhagen do not expressly teach the concentration of hydroxyalkyl methylcellulose is 0.1-10% by dry weight of the active ingredient.
However, the teachings of Hsiao above cure these deficiencies.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the presently claimed invention to modify a sustained release dosage form as claimed by the reference patent by optimizing the amount of hydroxyalkyl methylcellulose relative to the amount of drug, and as suggested in Hsiao with a reasonable expectation of success. The skilled artisan would have been motivated to optimize the amounts of ingredients within the ranges suggested by Hsiao to enable release of therapeutically effective amounts of drug over an extended time frame and in a controlled manner.
Accordingly, the subject matter of claims 1-15 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Conclusion
No claim is allowed.
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/WILLIAM CRAIGO/Examiner, Art Unit 1615
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