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 .
Abstract
The abstract of the disclosure is objected to because it does not appear on a separate page. Correction is required. See MPEP § 608.01(b).
The abstract of the disclosure does not commence on a separate sheet in accordance with 37 CFR 1.52(b)(4) and 1.72(b). A new abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text.
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 4-6 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 4 recites “gently re-dispersing the suspension”. The term “gently” is a relative term which renders the claim indefinite. The term “gently” 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. More specifically, the degree of agitation or amount of re-dispersive actions permitted that still fall within the scope of “gently” is not clear.
Claims that are rejected but not explicitly expounded upon are also indefinite because they depend from an indefinite claim and do not add clarity.
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 1-2 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Wieckhusen et al. (US Patent No. 8,227,488 – see IDS)
Wieckhusen et al. teach crystalline iloperidone in an injectable depot that is a suspension formulated for intramuscular injection (see abstract and column 1 lines 23-27 and lines 59-64 and column 5 lines 6-14). The drug is an anti-psychotic compound that is released over 2 to 8 weeks (see column 5 lines 6-14 and 36-38). Wieckhusen et al. teach the combination of particles in a vial with a liquid suspension vehicle, followed by shaking or swirling to yield a homogenous suspension, withdrawal by a syringe and injection (see column 5 lines 31-33 and examples 2-3; instant claims 1 and 7). Various doses are generated where 120 mg/ml and 425 mg/ml are employed in 1 ml or 2 ml volumes that yield a range of consistencies from a homogeneous liquid suspension to a homogeneous suspension paste that are separately injected into a subject (see examples 1-3). Wieckhusen et al. also teach a dosing range of 100 to 750 mg per injection (see column 5 lines 19-21; instant claims 22, 36, 42, 47, and 61-62). Average particle sizes are taught to range from 1 to 200 micron, where examples provide averages of 32 and 15 microns (see column 2 lines 25-30; instant claims 67-68). These exemplary sizes are less than 120 microns. While Wieckhusen et al. do not exemplify a composition of iloperidone with a concentration as instantly claimed, their teachings provide a range of concentrations that span from 120 to 425 mg/ml which embrace the claimed range and provide a variation in consistency that increases in viscosity with concentration. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to choose a concentration within the claimed range, including those claims that are claimed, as a matter of routine optimization because the concentration is a result effective variable. In addition, the claimed range is embraced by that of Wieckhusen et al. which renders the claimed range obvious. “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)” (see MPEP 2144.05). The recitation of iloperidone at about 600 mg in about 3 to 3.6 ml yields a total amount of iloperidone that falls within the range of 120 mg to 850 mg that were reconstituted in the examples and is near the upper end of the preferred range that is also taught. Given that the range implied by “about 600 mg” is embraced by both ranges it is obvious (see MPEP 2144.05). Therefore claims 1-2 and 7 are obvious over Wieckhusen et al.
Claims 1-2, 7-8, 12-13, and 15-20 are rejected under 35 U.S.C. 103 as being unpatentable over Wieckhusen et al. as applied to claims 1-2 and 7 above, and further in view of in view of Hickey et al. (US PGPub No. 2015/0265529 – see IDS).
Wieckhusen et al. render obvious the limitations of the injectable suspension depot of instant claims 1-2 and 7. Wieckhusen et al. do not detail the time for injection.
Hickey et al. teach the intramuscular injection of a particulate suspension depot anti-psychotic drug formulation (see paragraphs 2 and 5). They detail rapid injection of the depot suspension to overcome potential issues of injection site failures (see paragraph 43). Here a suspension is taught for intramuscular injection (see paragraphs 170-171 and 179; instant claims 12 and 20). An injection rate of 0.3 to about 1 ml/sec is taught as is injection within 5 seconds (see paragraphs 193 and 376; instant claims 8, 13, and 20). Known injection volumes for intramuscular injection are detailed to include 1.6 ml, 2 ml, 2.4 ml, and 3.2 ml (see table 2; instant claims 2, 15, and 18-19). Hickey et al. further teach an preparation and injection procedure, where the suspension is loaded into a syringe, then after 15 minutes without use, it is agitated to yield a homogeneous suspension (see example V; instant claim 16). They additionally turn the syringe upright to bring air to the top and expel the air along with a few drops of suspension in order to clear the air from the syringe (see example V; instant claims 17). The dose is then injected in a continuous rapid manner (single push) (see example V).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to apply the preparation of Hickey et al. to the vial/container contained depot of Wieckhusen et al. in the situation when injection has not occurred after 15 minutes from reconstitution, as Hickey et al. detail can occur. It also would have been obvious to follow the injection procedure of Hickey et al. for the composition of Wieckhusen et al. These modifications would have been obvious because both are anti-psychotic injectable suspension depots and as the application of the same technique to a similar product in order to yield the same improvement. This would then yield the syringe injection of a 1.6 ml, 2 ml, 2.4 ml, or 3.2 ml volume of a composition of Wieckhusen et al. at a continuous steady rate at 0.3 to 1 ml/sec which translates to 1.6 to 3.2 secs for administration at the fastest rate (see instant claims 8, 12-13, and 20). These volumes meet the instantly claimed volumes explicitly or due to the approximate nature of the claim limitations. The range and exemplified dosing levels and injection times yield a collection of dosing amounts and times that overlap with those instantly claimed (see MPEP 2144.05; instant claims 2, 15, and 18-19). Therefore claims 1-2, 7-8, 12-13, and 15-20 are obvious over Wieckhusen et al. in view of Hickey et al.
Claims 1-3 and 7-20 are rejected under 35 U.S.C. 103 as being unpatentable over Wieckhusen et al. in view of Hickey et al. as applied to claims 1-2, 7-8, 12-13, and 15-20 above, and further in view of Lambert et al. (WO 2008/142153) as evidenced by Zhang et al. (Drug Delivery 2015 22(3): 375–382 – see IDS).
Wieckhusen et al. in view of Hickey et al. render obvious the limitations of instant claims 18, 36, and 61. Their teachings render obvious the injection of about 1.25 ml to about 1.5 ml and about 2.5 to 3 ml as well as a dosing levels of about 166.67 to about 200 mg, about 500 mg, and about 250 mg. The exemplified and taught average size of the crystalline iloperidone particles of Wieckhusen et al., namely 1 to 200 microns, 15 microns, and 32 microns, also yields an overlapping range of Dv50 values relative to those instantly claimed and renders them obvious (see MPEP 2144.05). Wieckhusen et al. teach the suspension of the iloperidone in water as well as in a solution of mannitol, poloxamer 188 (called Pluronic® F68), and carboxymethyl cellulose sodium in a vial (see column 5 lines 31-33 and examples 2-3; Zhang et al. page 376 first column last partial paragraph; instant claims 9 and 14). The proportions of the excipients in the suspension vehicle are not detailed by Wieckhusen et al.
Lambert et al. teach a suspension vehicle for an injectable particulate drug depot (see abstract, page 11 fifth paragraph, and page 14 third paragraph following section “e”). They further teach 1 to 5 ml as well as 2 mL volumes injection volumes (see page 12 eighth paragraph). The suspension is prepared in an aqueous vehicle that includes water, mannitol, poloxamer 188 (called Pluronic® F68), and carboxymethyl cellulose sodium (see page 11 sixth paragraph and example 2). When included in a vial, the preferred vehicle contains 14 mg carboxymethyl cellulose sodium, 90 mg mannitol, and 4 mg poloxamer 188 in 2 ml (see example 2; instant claims 9 and 14).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to employ the suspension vehicle excipient proportions taught by Lambert et al. in the suspensions of Wieckhusen et al. in view of Hickey et al. This choice would have been obvious because they are preferred for vial preparations of injectable depots, as is employed in Wieckhusen et al. This then implicitly meets the limitations for the process steps where the excipients are added and the volume brought to 2 ml. The other volumes rendered obvious by Wieckhusen et al. in view of Hickey et al. are still obvious as well (see instant claims 10-11). Therefore claims 1-3 and 7-20 are obvious over Wieckhusen et al. in view of Hickey et al. and Lambert et al. as evidenced by Zhang et al.
Claims 1-2, 4, and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Wieckhusen et al. as applied to claims 1-2 and 7 above, and further in view of Andreef et al. (US PGPub No. 2004/0057989) and Fuchs et al. (US PGPub No. 2013/0302409).
Wieckhusen et al. render obvious the limitations of the injectable suspension depot method of production of instant claims 1-2 and 7. Wieckhusen et al. do not discuss all the instantly recited reconstitution details.
Andreef et al. also teach reconstitution of a dry drug powder into a suspension where a liquid medium is added to the drug particles in a vial and agitated to fully resuspend them (see paragraph 42-43 and 46). If foam occurs, they detail letting the vial stand (undisturbed) for a few minutes until the foam subsides (see paragraph 46). They then teach gently inverting the vial to redisperse any settled material and loading the suspension into a desired administration dispensing apparatus (see paragraph 46).
Fuchs et al. teach a particulate injectable drug depot that is reconstituted prior to injection (see abstract and paragraph 99). Here they detail mixing the particles well in the vehicle, drawing the suspension into a syringe, and injecting into the desired location within 10 to 30 seconds of syringe loading to avoid settling and potential clogging of the syringe (see paragraph 99).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to permit a shaken and reconstituted version of the composition of Wieckhusen et al. to sit undisturbed so that foam can dissipate in view of Andreef et al. The duration of this time period is a result effective and thus obvious to optimize as a matter of routine work which renders the instant duration obvious (see instant claim 4). It additionally would have been obvious to gently re-disperse any settled material in the container via inverting, loading a syringe and injecting within 10 to 30 seconds to avoid additional settling in the vial or syringe as Fuchs et al. teach can occur. The range of time between gentle redispersion and syringe loading overlaps with that instantly claimed, thereby rendering the claimed range obvious (see MPEP2144.05). Therefore claims 1-2, 4, and 7 are obvious over Wieckhusen et al. in view of Andreef et al. and Fuchs et al.
Claims 1-2, 4-8, 12-13, and 15-20 are rejected under 35 U.S.C. 103 as being unpatentable over Wieckhusen et al. in view of Andreef et al. and Fuchs et al.
as applied to claims 1-2, 4, and 7 above, and further in view of in view of Hickey et al.
Wieckhusen et al. in view of Andreef et al. and Fuchs et al. render obvious the limitations of the injectable suspension depot preparation of instant claims 1-2, 4, and 7. They do not detail removing any air from the syringe or exemplify the claimed administered volumes.
Hickey et al. teach the intramuscular injection of a particulate suspension depot anti-psychotic drug formulation (see paragraphs 2 and 5). They detail rapid injection of the depot suspension to overcome potential issues of injection site failures (see paragraph 43). Here a suspension is taught for intramuscular injection (see paragraphs 170-171 and 179; instant claims 12 and 20). An injection rate of 0.3 to about 1 ml/sec is taught as is injection within 5 seconds (see paragraphs 193 and 376; instant claims 8, 13, and 20). Known injection volumes for intramuscular injection are detailed to include 1.6 ml, 2 ml, 2.4 ml, and 3.2 ml (see table 2; instant claims 2, 15, and 18-19). Hickey et al. further teach loading the suspension in to a syringe, turning the syringe upright to bring air to the top and expelling the air along with a few drops of suspension in order to clear the air from the syringe (see example V; instant claims 17). The dose is then injected in a continuous rapid manner (single push) (see example V).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to employ the injection procedure of Hickey et al. for the modified composition of Wieckhusen et al. because both are anti-psychotic suspension depots. This modification would have been obvious as the application of the same technique to a similar product in order to yield the same improvement. This would then yield the syringe injection of a 1.6 ml, 2 ml, 2.4 ml, or 3.2 ml volume of a composition of Wieckhusen et al. at a continuous steady rate at 0.3 to 1 ml/sec which translates to 1.6 to 3.2 secs for administration at the fastest rate (see instant claims 8, 12-13, and 20). These volumes meet the instantly claimed volumes explicitly or due to the approximate nature of the claim limitations. The range and exemplified dosing levels and injection times yield a collection of dosing amounts and times that overlap with those instantly claimed (see MPEP 2144.05; instant claims 2, 15, and 18-19). Implementing the syringe loading technique of Hickey et al. also would have been obvious since it was known to be suitable for a similar composition. Therefore claims 1-2, 4-8, 12-13, and 15-20 are obvious over Wieckhusen et al. in view of Andreef et al., Fuchs et al., and Hickey et al.
Conclusion
No claim is allowed.
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/CARALYNNE E HELM/ Examiner, Art Unit 1615