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 . Claims included in the prosecution are claims 1, 2, 7, 8, 15, 23, 30, 47, 50, 51, 53, 54, 57-60, 64-67, 72-75, 81, 82, 89-91, 101, 103, 104, 109, 110, 114, 115, 118, 122 and 123.
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 02/26/2026 is acknowledged.
Claim Objections
Claim 59 is objected to because of the following informalities: “pregeletanized” should be recited as --- pregelatinized ---. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 103, 110 and 114 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 103 contains the trademark/trade name OPADRY® II. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a film coating and, accordingly, the identification/description is indefinite.
Claims 110 and 114 recites the limitation "valbenazine ditosylate" in the last line. There is insufficient antecedent basis for this limitation in the claim. Claim 1 does not recite wherein granule comprises valbenazine ditosylate. Therefore, the scope of valbenazine ditosylate is unclear.
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.
1. Claims 1, 2, 7, 51, 58, 65, 66, 73, 74, 82, 89-91, 104, 109, 110, 114, 115, 122 and 123 are rejected under 35 U.S.C. 103 as being unpatentable over McGee et al. (US 2017/0145008, May 25, 2017) (hereinafter McGee).
McGee discloses a pharmaceutical composition comprising a crystalline form of (S)-(2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-2,3,4,67,11b-hexahydro-1H-pyridol[2,1-a]isoquinolin-2-yl-amino-3-methylbutanoate di(4-methylbenezenesulfonate) (¶ [0013]). The compound may be valbenazine ditosylate (¶ [0088]). The pharmaceutical composition may be fabricated in a multiparticulate controlled release device, which comprises a multiplicity of particles, granules, or pellets, ranging from about 10 µm to about 3 mm in diameter (¶ [0277]). Excipients may be blended with the pharmaceutical composition to aid in processing and forming the multiparticulates. The resulting particles may be coated by various film forming materials. The multiparticulates can be further processed as a capsule (¶ [0278]). Suitable excipients include diluents, disintegrants, binders, and lubricant (¶ [0215]). Suitable disintegrants include pre-gelatinized starch (¶ [0218]). Suitable binders include hydroxypropyl methyl cellulose (¶ [0216]). Suitable lubricants include magnesium stearate (¶ [0219]). In the treatment, prevention, or amelioration of one or more symptoms of hyperkinetic disorder or other conditions, disorders or diseases associated with VMAT2 inhibition, an appropriate dosage level generally is about 0.001 to 100 mg per kg patient body weight per day (mg/kg per day) (¶ [0287]). It will be understood, however, that the specific dose level and frequency of dosage for any particular patient may be varied and will depend upon a variety of factors including the activity of the specific compound employed, the metabolic stability and length of action of that compound, the age, body weight, general health, sex, diet, mode and time of administration, rate of excretion, drug combination, the severity of the particular condition, and the host undergoing therapy (¶ [0289]). The pharmaceutical composition may be provided in unit dosage forms (¶ [0212]).
McGee differs from the instant claims insofar as not disclosing specifically an average diameter of at least 1 mm.
However. McKee discloses about 10 µm to about 3 mm in diameter, which overlaps with the claimed range. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art”, a prima facie case of obviousness exists. MPEP 2144.05 A. Therefore, the instant claims are obvious.
In regards to instant claims 82, 89, 90, 104, 109, 110, 114, 122, and 123 reciting an amount of valbenazine or a pharmaceutically acceptable salt thereof, McGee discloses a dosage of about 0.001 to 100 mg per kg patient body weight per day (mg/kg per day) and wherein the specific dose level for any particular patient may be varied and will depend upon a variety of factors including the activity of the specific compound employed, the metabolic stability and length of action of that compound, the age, body weight, general health, sex, diet, mode and time of administration, rate of excretion, drug combination, the severity of the particular condition, and the host undergoing therapy. Accordingly, it would have taken no more than the relative skills of one of ordinary skill in the art through routine optimization to have arrived at the claimed amount of valbenazine or a pharmaceutically acceptable salt depending on the activity of the specific compound employed, the metabolic stability and length of action of that compound, the age, body weight, general health, sex, diet, mode and time of administration, rate of excretion, drug combination, the severity of the particular condition, and the host undergoing therapy.
2. Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over McGee et al. (US 2017/0145008, May 25, 2017) (hereinafter McGee) in view of Park et al. (US 2011/0223247, Sep. 15, 2011) (hereinafter Park).
The teachings of McGee are discussed above. McGee does not teach wherein each granule has a diameter variation of no more than 20% from the average diameter.
However, Park discloses a pharmaceutical composition for release control comprising a plurality of particles for release control (abstract). The particles comprise a core material and a polymer coating formed on the core material (¶ [0018]). The diameter of the core material may be determined using a particle size analyze. The diameter deviation indicates the degree of variation from the average particle diameter. The smaller the diameter deviation is, a more uniform coating thickness may be obtained. With a more uniform coating thickness, it is easier to obtain reproducible results since the active ingredient of the drug is released uniformly (¶ [0024]).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to formulated the granules to have the smallest diameter variation possible since this would produce granules with a uniform coating thickness and with a more uniform coating thickness, it is easier to obtain reproducible results as taught by Park.
3. Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over McGee et al. (US 2017/0145008, May 25, 2017) (hereinafter McGee) in view of Levin et al. (US 2005/0025811, Feb. 3, 2005) (hereinafter Levin).
The teachings of McGee are discussed above. McGee does not teach wherein each granule has an average density of about 0.75 g/cm3 to about 2.5 g/cm3.
However, Levin discloses granulations useful in pharmaceutical tableting (abstract). The granulated composition has a free-flowing quality and a dense, sand-like texture. Preferred granulations have an average tap density between about 0.9 and about 2.0 g/cm3 (¶ [0038]).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have formulated the granules to have an average tap density of between about 0.9 and about 2.0 g/cm3 motivated by the desire to have free-flowing granules, which is desirable in the pharmaceutical art as taught by Levin.
In regards to instant claim 15 reciting a d99 particle diameter distribution of at most about 2.8 mm, a range of about 2.8 mm encompasses 3 mm and McGee discloses a diameter of about 10 µm to about 3 mm. Thus, the claimed d99 particle diameter would have been obvious since McGee discloses a diameter of no more than 3 mm.
4. Claims 23 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over McGee et al. (US 2017/0145008, May 25, 2017) (hereinafter McGee) in view of Celiker (US 2020/0078397, Mar. 12, 2020).
The teachings of McGee are discussed above. McGee does not teach wherein each granule has an average weight of about 8 mg to about 10.2 mg.
However, Celiker discloses a pharmaceutical composition comprising a plurality of particles (abstract). Average weight of each coated particle may be 0.96 ± 0.07 mg (¶ [0193]).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have formulated each granule to have an average weight of 0.96 ± 0.07 mg since McGee does not disclose what the average weight is and this is a known and effective average weight for granules in pharmaceutical compositions as taught by Celiker.
5. Claims 47 and 50 are rejected under 35 U.S.C. 103 as being unpatentable over McGee et al. (US 2017/0145008, May 25, 2017) (hereinafter McGee) in view of Shah et al. (MA 42153 A1, Jan. 31, 2019) (hereinafter Shah).
The teachings of McGee are discussed above. McGee does not teach wherein the film coating comprises about 25 wt. % to about 55 wt. % poly(vinyl alcohol), about 5 wt. % to about 30 wt. % polyethylene glycol, about 5 wt. % to about 45 wt. % talc, and up to about 40 wt. % titanium dioxide, based on the weight of the film-coating, and wherein the film-coating makes up about 3.5 wt. % to about 15 wt. % of each granule.
However, Shah discloses tablets that are film-coated. The amount of coating applied is 3%. The coating consists of 1.2% poly(vinyl alcohol) (40% of coating), 0.6234% titanium dioxide (21% of coating), 0.606% polyethylene glycol (20% of coating), 0.444% talc (15% of coating), 0.099% yellow iron oxide, 0.024% red iron oxide, and 0.0036% black iron oxide. The amount of film coating can reach 5% of the weight of the core (page 17 of 19 of translation).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have incorporated 3% (meeting about 3.5%) of the film coating of Shah onto each granule of McGee since this is a known and effective film coating for pharmaceuticals and amount thereof as taught by Shah.
6. Claim 53 is rejected under 35 U.S.C. 103 as being unpatentable over McGee et al. (US 2017/0145008, May 25, 2017) (hereinafter McGee) in view of Huguet Riba et al. (US 2009/0155369, Jun. 18, 2009) (hereinafter Huguet Riba).
The teachings of McGee are discussed above. McGee does not teach wherein the diluent is a mixture of silicified microcrystalline cellulose and isomalt.
However, Huguet Riba discloses a solid pharmaceutical composition comprising entacapone, levodopa, and caribidopa, wherein entacapone is in the form of granules (abstract). Levodopa and carbidopa may be together in the form of granules (¶ [0013]). The granules may comprise at least one diluent agent (¶ [0025]). Suitable diluents include salified microcrystalline, isomalt, and mixtures thereof (¶ [0027]).
Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. McGee discloses wherein the granules comprises a diluent. Accordingly, it would have been obvious to one of ordinary skill in the art to have incorporated silicified microcrystalline cellulose and isomalt onto the granules of McGee since silicified microcrystalline cellulose and isomalt are known and effective diluents as taught by Huguet Riba.
7. Claims 54, 57, 60, 64, 67, 72, 75 and 81 are rejected under 35 U.S.C. 103 as being unpatentable over McGee et al. (US 2017/0145008, May 25, 2017) (hereinafter McGee) in view of Bergman et al. (WO 2007/104907 A1, Sep. 20, 2007) (hereinafter Bergman).
The teachings of McGee are discussed above. McGee does not teach the amount of lubricant, binder, disintegrant, and diluent for each granule.
However, Bergman discloses that many types of excipients are known to the skilled person. For instance, a pre-granulation mixture will often comprise diluents, which make the formulation up to an appropriate size, and one or more disintegrants, which expand upon absorption of water, helping to break apart a solid formulation after ingestion. A binder may be used to hold the ingredients inside each granule, and a lubricant may be incorporated after granulation to prevent the granules sticking to an equipment used during tableting process (page 3, lines 4-12).
Accordingly, it would have taken no more than the relative skills of one of ordinary skill in the art to have arrived at the claimed amount of diluent through routine experimentation based on the size of the granule desired as taught by Bergman.
Also, it would have taken no more than the relative skills of one of ordinary skill in the art to have arrived at the claimed amount of disintegrant through routine experimentation based on the amount needed to have the granules break apart after ingestion as taught by Bergman.
Additionally, it would have taken no more than the relative skills of one of ordinary skill in the art to have arrived at the claimed amount of binder through routine experimentation based on the amount needed to hold the ingredients together inside each granule as taught by Bergman.
Finally, it would have taken no more than the relative skills of one of ordinary skill in the art to have arrived at the claimed amount of lubricant through routine experimentation based on the amount needed to inhibit stickiness as taught by Bergman.
Where 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. See MPEP 2144.05(II)(A).
8. Claim 59 is rejected under 35 U.S.C. 103 as being unpatentable over McGee et al. (US 2017/0145008, May 25, 2017) (hereinafter McGee) in view of Jain et al. (US 2011/0008426, Jan. 13, 2011) (hereinafter Jain).
The teachings of McGee are discussed above. McGee does not teach wherein the granules comprise partially pregelatinized maize starch.
However, Jain discloses a modified release pharmaceutical composition (abstract). Suitable disintegrants used for the composition include partially pregelatinized maize starch.
Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. McGee discloses wherein the granules comprises a disintegrant. Accordingly, it would have been obvious to one of ordinary skill in the art to have incorporated partially pregelatinized maize starch onto the granules since it is a known and effective disintegrant for pharmaceutical compositions as taught by Jain.
9. Claim 101 is rejected under 35 U.S.C. 103 as being unpatentable over McGee et al. (US 2017/0145008, May 25, 2017) (hereinafter McGee) in view of Bergman et al. (WO 2007/104907 A1, Sep. 20, 2007) (hereinafter Bergman), and further in view of Huguet Riba et al. (US 2009/0155369, Jun. 18, 2009) (hereinafter Huguet Riba), Jain et al. (US 2011/0008426, Jan. 13, 2011) (hereinafter Jain), and Ochiai et al. (US 2003/0039699, Feb. 27, 2003) (hereinafter Ochiai).
The teachings of McGee and Bergman are discussed above. McGee and Bergman do not teach wherein the diluent is a mixture of silicified microcrystalline cellulose and isomalt.
However, Huguet Riba discloses a solid pharmaceutical composition comprising entacapone, levodopa, and caribidopa, wherein entacapone is in the form of granules (abstract). Levodopa and carbidopa may be together in the form of granules (¶ [0013]). The granules may comprise at least one diluent agent (¶ [0025]). Suitable diluents include salified microcrystalline, isomalt, and mixtures thereof (¶ [0027]).
Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. McGee discloses wherein the granules comprises a diluent. Accordingly, it would have been obvious to one of ordinary skill in the art to have incorporated silicified microcrystalline cellulose and isomalt onto the granules of McGee since silicified microcrystalline cellulose and isomalt are known and effective diluents as taught by Huguet Riba.
The combined teachings of McGee, Bergman, and Huguet Riba do not teach wherein the granules comprise partially pregelatinized maize starch.
However, Jain discloses a modified release pharmaceutical composition (abstract). Suitable disintegrants used for the composition include partially pregelatinized maize starch.
Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. McGee discloses wherein the granules comprises a disintegrant. Accordingly, it would have been obvious to one of ordinary skill in the art to have incorporated partially pregelatinized maize starch onto the granules since it is a known and effective disintegrant for pharmaceutical compositions as taught by Jain.
The combined teachings of McGee, Bergmann, Huguet Riba, and Jain do not teach wherein the film-coating is about 8.2 wt. % to about 10.5 wt. %.
However, Ochiai discloses coated granules (abstract). An enteric coating agent is contained in an amount of 10% -50% of the granule (¶ [0082]).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have incorporated 10% to 50% of film-coating onto the granules of McGee since McGee does not disclose an amount of film-coating and this is a known and effective amount of film coating on a drug granule as taught by Ochiai.
10. Claim 103 is rejected under 35 U.S.C. 103 as being unpatentable over McGee et al. (US 2017/0145008, May 25, 2017) (hereinafter McGee) in view of Bergman et al. (WO 2007/104907 A1, Sep. 20, 2007) (hereinafter Bergman), Huguet Riba et al. (US 2009/0155369, Jun. 18, 2009) (hereinafter Huguet Riba), Jain et al. (US 2011/0008426, Jan. 13, 2011) (hereinafter Jain), Ochiai et al. (US 2003/0039699, Feb. 27, 2003) (hereinafter Ochiai)., and further in view of Wang et al. (US 2012/0115799, May 10, 2012) (hereinafter Wang).
The teachings of McGee, Bergman, Huguet Riba, Jain, and Ochiai are discussed above. McGee, Bergman, Huguet Riba, Jain, and Ochiai do not teach wherein the film-coating is OPADRY® II.
However, Wang discloses an oral dosage form that be in the form of granules (¶ [0094]). Opadry II was utilized as a film coating (¶ [0150]).
Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. McGee discloses wherein the granules comprises a film coating. Accordingly, it would have been obvious to one of ordinary skill in the art to have incorporated Opadry II onto the granules of McGee since it is a known and effective film coating material as taught by Wang.
11. Claim 118 is rejected under 35 U.S.C. 103 as being unpatentable over McGee et al. (US 2017/0145008, May 25, 2017) (hereinafter McGee) in view of Lim et al. (US 2016/0199302, Jul. 14, 2016) (hereinafter Lim).
The teachings of McGee are discussed above. McGee does not teach wherein the capsule is a size 0.
However, Lim discloses dry granules (abstract). Capsules may be filled with the granule mixture (¶ [0025]). The capsule may be a 0-size capsule (¶ [0070]).
McGee discloses wherein the multiparticulates can be further processed as a capsule. Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have formulated the capsule to be a size 0 since this is a known and effective capsule size for capsules comprising granules as taught by Lim.
Conclusion
Claims 1, 2, 7, 8, 15, 23, 30, 47, 50, 51, 53, 54, 57-60, 64-67, 72-75, 81, 82, 89-91, 101, 103, 104, 109, 110, 114, 115, 118, 122 and 123 are rejected.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TRACY LIU whose telephone number is (571)270-5115. The examiner can normally be reached Mon-Fri 9 am - 5 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached at 571-272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/TRACY LIU/Primary Examiner, Art Unit 1614