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 .
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.
Claim 17 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The claim recites “wherein the unit dose is administered with the help of an autoinjector,” and it is unclear in what way the autoinjector is to “help” administer the unit dose. For purposes of examination, the claim will be interpreted as simply administered with an autoinjector.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-7, 9, 16, 18 and 19, are rejected under 35 U.S.C. 102(a)(1) as being anticipated by APOKYN (APOKYN apomorphine hydrochloride injection, 2010, pp. 1-45), as evidenced by El-Rashidy et al (US 20030073715 A1) and Dey et al (US 20140128422 A1).
The reference discloses APOKYN is a subcutaneous apomorphine hydrochloride injection comprising 10 mg/mL apomorphine HCl, sodium metabisulfite, water for injection, and may also contain benzyl alcohol (pg. 1, 45). The injection is present as a unit dose in a dosing pen (pg. 19, 32). As evidenced by El-Rashidy et al, sodium metabisulfite is a stabilizer and antioxidant (¶ 42). As evidenced by Dey et al, APOKYN has a pH range of 3.0-4.0 (¶ 3).
Regarding claim 1, APOKYN comprises apomorphine hydrochloride and water (pharmaceutically acceptable carrier), and is present as a unit dose in a device.
Regarding claim 2, APOKYN is present as a unit dose in a pen injector.
Regarding claim 3, where APOKYN is an injectable solution, it appears the composition would be capable of being present in any device suitable for injection, such as an autoinjector, thereby meeting the intended use limitation.
Regarding claims 4 and 5, apomorphine hydrochloride is present in a concentration of 10 mg/mL, falling within the claimed ranges.
Regarding claim 6, the reference teaches APOKYN is suitable for subcutaneous administration.
Regarding claims 7 and 9, APOKYN comprises sodium metabisulfite (stabilizer and antioxidant).
Regarding claim 16, APOKYN has a pH range of 3.0-4.0, as evidenced by Dey et al.
Regarding claims 18 and 19, where the pharmaceutical composition as instantly claimed is anticipated above, and is present in a unit dose device, it appears the composition would be capable of being packaged in a blister packaging or aluminum pouch under vacuum, thereby meeting the intended use limitation.
Claims 1-3, 7, 9, 10, 15, 18, and 19, are rejected under 35 U.S.C. 102(a)(1) or (a)(2) as being anticipated by El-Rashidy et al (US 20030073715 A1).
El-Rashidy et al disclose a liquid apomorphine-containing dosage form comprising apomorphine, sodium metabisulfite (antioxidant), and ethylenediamine tetraacetic acid (EDTA), that can be administered via sublingual route (abs, ¶ 76).
Regarding claim 1, El-Rashidy et al disclose a liquid composition comprising apomorphine.
Regarding the pharmaceutically acceptable carrier of claim 1, where the dosage form is in the form of a liquid, and can be administered sublingually, it appears the liquid reads on a pharmaceutically acceptable carrier.
Regarding the device of claims 1 and 2, where the composition is anticipated above and is disclosed as a liquid formulation suitable for administration sublingually, it appears the liquid composition would be capable of being present as a unit does in a device, such as a prefilled syringe, etc., thereby meeting the intended use limitation.
Regarding claim 3, where the composition disclosed by El-Rashidy et al is in liquid form, it appears the composition would be capable of being present in any device suitable for liquids, such as an autoinjector, thereby meeting the intended use limitation.
Regarding claim 7, the composition of El-Rashidy et al above comprises sodium metabisulfite (antioxidant).
Regarding claims 9 and 10, the composition of El-Rashidy et al above comprises EDTA, thereby meeting the claim limitations.
Regarding claim 15, there appears to be no preservatives in the liquid dosage form of El-Rashidy et al, and therefore meets the limitation of being substantially free of preservatives.
Regarding claim 18 and 19, where the pharmaceutical composition as instantly claimed is anticipated above, it appears the composition would be capable of being packaged in a blister packaging or aluminum pouch under vacuum, thereby meeting the intended use limitation.
Claims 1-7, 9, 11-16, and 18-20, are rejected under 35 U.S.C. 102(a)(1) or (a)(2) as being anticipated by Schnait et al (US 20180280465 A1).
Schnait et al disclose aqueous compositions comprising apomorphine and a carrier for subcutaneous administration (abs, ¶ 62, table 12, claim 1). The aqueous composition can be directly administered as a ready to use composition via subcutaneous injection using a prefilled injection pen (¶ 46). In embodiments, the apomorphine composition is injected (¶¶ 72, 102). In embodiments, the aqueous composition comprises about 5 mg/ml of apomorphine or a pharmaceutically acceptable salt thereof (¶ 46, table 12). In embodiments, the composition further comprises reduced glutathione (antioxidant), ascorbic acid, sodium chloride, etc., with a pH of 4 (table 12). The compositions have high stability to oxidative degradation, due to the antioxidative behavior of the combination of reduced glutathione and ascorbate (¶ 208). Ascorbic acid is disclosed as both an antioxidant and a buffer (¶ 58). In embodiments, apomorphine is used in combination with citrate, mannitol, etc. (table 9). Table 13 discloses embodiments wherein the impurities as high as 0.08 wt% and as low as 0.06 wt% (table 13). Comparative data on apomorphine assay was determined by an HPLC method (¶ 235). The composition may optionally further comprise preservatives, etc. (¶ 65).
Regarding the composition claim 1, Schnait et al teach embodiment comprising apomorphine and a pharmaceutically acceptable carrier (i.e., water).
Regarding the device of claims 1 and 2, where the composition is anticipated above and is disclosed as suitable for administration via subcutaneous injection using a prefilled injection pen, the composition is capable of meeting the intended use limitation of being present as a unit dose in a device. Nevertheless, where Schnait et al disclose embodiments as instantly claimed that are injected, the compositions necessarily were present as a unit dose in a device, where a device is required for injecting aqueous compositions.
Regarding claim 3, where the claim is directed to a composition comprising apomorphine and a pharmaceutically acceptable carrier, it appears the limitation of the composition being present as a unit dose in an autoinjector is simply an intended use limitation. As such, where the composition of Schnait et al are disclose as suitable for injection, it appears that the composition of Schnait et al would be capable of being present as a unit dose in an autoinjector, thereby meeting the intended use limitation.
Regarding claims 4 and 5, Schnait et al discloses embodiments as instantly claimed comprising 5 mg/ml apomorphine.
Regarding claim 6, where the compositions of Schnait et al are disclosed as suitable for subcutaneous administration, the limitation is met.
Regarding claim 7, Schnait et al discloses embodiments as instantly claimed comprising antioxidants.
Regarding claim 9, where the instant specification defines the term “stabilizer” as a compound which inhibits or prevent the degradation of apomorphine, it appears that the antioxidants disclosed by Schnait et al read on a stabilizer, where the antioxidants are disclosed as reducing oxidative degradation to produce highly stable compositions (see pg. 4 of the instant specification).
Regarding claim 11, where Schnait et al discloses an embodiment as instantly claimed comprising ascorbic acid, a buffer, as taught by Schnait et al, the limitation of further comprising one or more buffering agents is met.
Regarding claim 12, Schnait et al discloses embodiments as instantly claimed comprising citrate buffer.
Regarding claims 13 and 14, Schnait et al discloses embodiments as instantly claimed comprising sodium chloride and mannitol.
Regarding claim 15, the working embodiments from table 12 of Schnait et al do not appear to comprise a preservative, thereby meeting the claim limitation.
Regarding claim 16, table 12 of Schnait et al discloses an embodiment as instantly claimed with a pH of 4, falling within the claimed range.
Regarding claims 18 and 19, where the claim is directed to a composition comprising apomorphine and a pharmaceutically acceptable carrier, it appears the limitation of being packed in a blister package or aluminum pouch as instantly claimed is simply an intended use limitation of the composition. As such, while Schnait et al do not specifically disclose the packaging of claims 18 and 19, it would be reasonably expected that the composition would be capable of being packed under vacuum in a blister packaging comprising an oxygen absorber or packaged in an aluminum pouch under vacuum, as instantly claimed.
Regarding claim 20, where Schnait et al discloses embodiments as instantly claimed comprising apomorphine impurities of 0.08 and 0.07 wt%, the limitation of comprising no more than 0.5 wt% morphine impurity is met. Further, Schnait et al discuss the comparative data for apomorphine was measured by using an HPLC method.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 2, 4-7, 9, 11-16, and 18-20, are rejected under 35 U.S.C. 103 as being unpatentable over Schnait et al (US 20180280465 A1).
Schnait et al are discussed above, and purely en arguendo, if the limitation of being present in a unit does in a device is a required structural limitation, and not simply intended use, and the composition is not necessarily present in a unit dose device, the following applies. Further, purely en arguendo, if one of the components in the embodiments from table 12 of Schnait et al were to also read on a preservative, the following also applies.
Regarding claim 1, Schnait et al teach embodiment comprising apomorphine and a pharmaceutically acceptable carrier (i.e., water).
Regarding the device of claims 1 and 2, purely en arguendo, if the limitation of being present in a unit dose in a device is not simply intended use and the composition is not necessarily present in a unit dose device, then it would have been obvious to include the composition as a unit dose in a device, such as a prefilled pen, as taught by Schnait et al.
Regarding claim 15, purely en arguendo, if one the components in the embodiments from table 12 of Schnait et al were to also read on a preservative, it would have been obvious to formulate the composition substantially free of a preservative, where the inclusion of a preservative is taught to be optional.
Regarding claims 4-7, 9, 11-14, 16, and 18-20, the claims are rejected in view of Schnait et al for the same reasons above and of record as applied to each claim limitation.
Claims 3 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Schnait et al (US 20180280465 A1), as applied to claims 1, 2, 4-7, 9, 11-16, and 18-20 above, and further in view of Prestrelski et al (US 20180369255 A1).
Schnait et al are discussed above and further teach the subject to be treated may be a mammal (¶ 79).
Schnait et al are discussed above, and purely en arguendo, if the autoinjector is not simply an intended use of the composition of claim 1, the following applies. The reference does not disclose a method of administering the composition to a mammal via an autoinjector as instantly claimed.
Prestrelski et al teach injectable formulations of small molecule drugs, such as apomorphine, where it was known to include apomorphine in an autoinjector (abs, ¶¶ 14, 17, 48, 51, 64, claim 7).
Regarding claim 3, even if purely en arguendo, the prior art does not anticipate the claims, it would have been obvious to include the apomorphine composition in an autoinjector, where autoinjectors were known to be suitable for injectable compositions comprising apomorphine, as taught by Prestrelski et al.
Regarding claim 17, it would have been obvious to administer the apomorphine composition of Schnait et al to a mammal via an autoinjector, for the same reasons discussed above by Prestrelski et al, thereby meeting the intended use limitation of the composition of claim 1.
Claims 8 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Schnait et al (US 20180280465 A1), as applied to claims 1-7, 9, 11-16, and 18-20 above, and further in view of Gupta et al (US 20020002176 A1) and Ang et al (Drug Design, Dev. And Ther., 2016, 10, pp. 3253-3265).
Schnait et al are discussed above but do not teach the antioxidants of claim 8, nor embodiments comprising EDTA of claim 10.
Gupta et al teach pharmaceutical compositions comprising apomorphine and a pharmaceutically acceptable carrier, where it was known to include antioxidants including sodium formaldehyde sulfoxylate (abs, ¶¶ 19, 46). Further, it was known to further include chelating agents, such as ethylene diamine tetraacetic acid (¶ 47).
Ang et al teach stable apomorphine HCl solutions comprising an antioxidant and EDTA solution (abs). The compositions comprising EDTA remained stable for at least 72 hours, which was longer than those without EDTA (conclusion). All samples changed color except for the sodium metabisulfite + ascorbic acid, the sodium metabisulfite + EDTA solutions, and the ascorbic acid + EDTA solutions (table 2).
Regarding claim 8, where Schnait et al disclose compositions comprising apomorphine and antioxidants, it would have been obvious to use other known antioxidants suitable for pharmaceutical compositions comprising apomorphine, such as sodium formaldehyde sulfoxylate, as taught by Gupta et al.
Regarding claim 10, it would have been obvious to modify the composition of Schnait et al by including known chelating agents suitable for pharmaceutical compositions comprising apomorphine, such as ethylene diamine tetraacetic acid (EDTA), as taught by Gupta et al. Additional motivation for including EDTA is provided by Ang et al, where it was known to include EDTA as a stabilizer for compositions comprising apomorphine, where EDTA used in combination with an antioxidant appears to result in increased stability of the apomorphine compositions, as taught by Ang et al.
Claims 18 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Schnait et al (US 20180280465 A1), as applied to claims 1-7, 9, 11-16, and 20 above, and further in view of Devouassoux et al (US 20140262883 A1).
Schnait et al are discussed above, and purely en arguendo, if the packaging is not simply an intended use of the composition of claim 1, the following applies.
Devouassoux et al teach pharmaceutical packaging systems which prevent oxygen degradation of oxygen-sensitive drugs, such as morphine, wherein the packaging comprises an oxygen absorber (abs). The packing may be a bag or blister packaging (¶¶ 5, 10, 12). The bag or blister packaging comprises an oxygen barrier material, such as aluminum foil (¶ 5). The packaging may undergo vacuumization (¶¶ 47, 64, 96).
Regarding claim 18, even if purely en arguendo, the prior art does not anticipate the claims, it would have been obvious to include the composition of Schnait et al in a blister packaging comprising an oxygen absorber, wherein the packaging is under vacuum, as taught by Devouassoux et al, in order to prevent oxidative degradation of apomorphine.
Regarding claim 19, even if purely en arguendo, the prior art does not anticipate the claims, it would have been obvious to include the composition of Schnait et al in an aluminum pouch under vacuum, as taught by Devouassoux et al, in order to prevent oxidative degradation of apomorphine.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSHUA A ATKINSON whose telephone number is (571)270-0877. The examiner can normally be reached M-F: 9:00 AM - 5:00 PM + Flex.
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, Frederick Krass can be reached at 571-272-0580. 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.
/JOSHUA A ATKINSON/Examiner, Art Unit 1612