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 .
Request for Continued Examination
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant’s submission filed on 02/28/2022 has been entered.
DETAILED ACTION
Claims 21, 24-32 and 34-42 are pending in the Claim Set filed 2/4/2026
Claim 1 has been amended. Claims 40-42 are newly added.
Claims 1-20, 22 and 23 are cancelled.
Herein, claims 21 and 24-42 are for examination.
Notice Regarding Claims
Applicants’ attention is directed to MPEP 714 C (4) (i): No claim text shall be presented for any claim in the claim listing with the status of ‘canceled’.
Regarding canceled claim 33: The text of the claim must not be presented. Future claim amendments should not contain the text of canceled claims.
Withdrawn Rejections
The rejection of claim 33 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. Is withdrawn in view of the claim amendments.
The rejection of claims 21 and 24-39 are rejected under 35 U.S.C. 103 as being unpatentable over Kavey et al (USP 6211229, of record) [Kavey] in view of Rogowski et al (US 2007/0281990, of record) [Rogowski], Mulye (US 20040224017, of record) [Mulye] and Takeo et al (USP 4159345) [Takeo] is withdrawn in view of the claim amendments in favor the New Grounds of Rejection as shown below.
The rejection of Claims 21 and 24-39 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4-9 and 11-20 of U.S. Patent No. 11096920 (herein ‘920) in view of Mulye (US 20040224017, of record) and Takeo et al (USP 4159345) is withdrawn in view of the claim amendments in favor the New Grounds of Rejection as shown below.
The rejection of Claims 21 and 24-39 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10548871 (herein ‘871) in view of Mulye (US 20040224017, of record) and Takeo et al (USP 4159345) is withdrawn in view of the claim amendments in favor the New Grounds of Rejection as shown below.
The rejection of Claims 21 and 24-39 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4-13 and 14-20 of U.S. Patent No. 9907780 (herein ‘780) in view of Mulye (US 20040224017, of record) and Takeo et al (USP 4159345) is withdrawn in view of the claim amendments in favor the New Grounds of Rejection as shown below.
The rejection of Claims 21 and 24-39 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 9532971 (herein ‘971) in view of Mulye (US 20040224017, of record) and Takeo et al (USP 4159345) is withdrawn in view of the claim amendments in favor the New Grounds of Rejection as shown below.
Status of Canceled Claim 33
Claim 33 is noted as being canceled. However, per 37 C.F.R. 1.121, a claim being canceled must be indicated as canceled and the text of the claim must not be present (see MPEP 714). Therefore, the text of the claim should be deleted.
New Grounds of Rejection
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.
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 21, 24-39 and 41-42 are rejected under 35 U.S.C. 103 as being unpatentable over Kavey et al (USP 6211229, of record) [Kavey] in view of Rogowski et al (US 2007/0281990, of record) [Rogowski], Mulye (US 20040224017, of record) [Mulye], as evidenced by Specification.
Regarding claims 21, 25-29, 31-35, 41 and 42,
Kavey teaches a method for treating chronic and non-chronic forms of insomnia comprising administration of doxepin, or pharmaceutically acceptable forms of doxepin, in an amount ranging from about 0.5 to 20 mg. (Abstract; col.1, lns.51-53; Examples 1-26). In particular, Kavey teaches treatment comprising administration of doxepin in an amount is about 10 mg, 5 mg or less, and 2 mg (col.9, claims 1-516, 17-31; col.4, line 27). Further, Kavey teaches that doxepin is administered for the treatment of onset and/or maintenance insomnia (col.2, lns.58-63; Examples 1-13 (onset); Examples 14-26). Kavey teaches pharmaceutically acceptable forms of doxepin include injectable solutions, capsules and caplets (col.3, lns.31-40).
Accordingly, administration of doxepin in the range of about 2 mg to 10 mg in a method for a treating chronic and non-chronic forms of insomnia as taught by Kavey overlaps with the amounts in claims 21, 25, 26, 27, 28 and 29. Further, a method for treating chronic and non-chronic forms of insomnia (Instant Claims 31-33) and wherein a patient suffers from difficulties in sleep onset Instant Claim 34) and sleep maintenance (Instant Claim 35) is taught by Kavey.
Kavey differs from the claims in that the document does not teach that the administering the composition provides a plasma concentration of at least 0.1 ng/ml doxepin within a time frame of not more than about 60 minutes; wherein the amount of microcrystalline cellulose is about 50% to about 80% w/w.
However, Rogowski and Mulye, as a whole, as evidenced by Specification, cure the deficiencies.
Rogowski teaches methods of using low-dose doxepin for the improvement of sleep (Title). Rogowski teaches methods of preventing early awakenings, and improving sleep efficiency in hours 7 and 8 of a period of sleep, by administration of low doses of doxepin, for example, 1, 3 and 6 mg, e.g., 1-6 mg of doxepin (See Abstract; [0012]; [0037]: low dose is between 0.5 and 6 mg; [0073]; [0076-0080: tablets]; [0090: carrier material that facilitates formation into a tablet]; claims 1-22; See entire document). Particularly, Rogowski teaches a doxepin plasma concentration of at least 0.1 ng/mL within 60 minutes using a tablet or a capsule containing about 1-6 mg of doxepin (See Figure 2, shown below; [0015]).
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In accordance with the results displayed in Figure 2, it would have been obvious to one of ordinary skill in the art before the effective filing date of the invention that administration of about 1-6 mg of doxepin that doxepin plasma concentration would be equal to or greater than 0.1 ng/ml doxepin within a time frame of not more than about 60 minutes in a method of improving sleep efficiency in hours 7 and 8 of a period of sleep as taught by Rogowski. Moreover, Rogowski teaches the methods described herein can be used to treat individuals suffering from a sleep disorder, such as insomnia. The individual can suffer from a chronic insomnia or a non-chronic insonmia. For chronic (e.g., greater than 3-4weeks) or non-chronic insonmias, a patient may suffer from difficulties in sleep onset, sleep maintenance (interruption of sleep during the night by periods of wakefulness), sleep duration, sleep efficiency, premature early-morning awakening or a combination thereof [0075]. Rogowski teaches the compositions and formulations disclosed herein include one or more pharmaceutically acceptable carrier materials or excipients. The term carrier can mean any substance, not itself a therapeutic agent, used as a carrier and/or diluent and/or adjuvant, or vehicle for delivery of a therapeutic agent to a subject or added to a pharmaceutical composition to improve its handling or storage properties or to permit or facilitate formation of a dose unit of the composition into a discrete article such as a capsule or tablet suitable for oral administration [0090].
Kavey teaches (above) pharmaceutically acceptable forms of doxepin include capsules and caplets (col.3, lns.31-40), of which is the same or similar to the form of administering doxepin as shown in Figure 2.
Thus, it would necessarily follow that by administering of about 1-6 mg doxepin to a patient as taught by Kavey and Rogowski, as a whole, that the doxepin plasma concentration would be at 0.1 ng/ml doxepin within a time frame of not more than about 60 minutes.
Mulye teaches pharmaceutical unit dosage form for administration of medicinal compounds comprising doxepin and excipients comprising microcrystalline cellulose, wherein microcrystalline cellulose is present in formulations from about 5% to about 65% by weight ([0039]; [0045-0046; See entire document), of which the amounts of microcrystalline cellulose (MCC) of about 5-65% wt overlap with the claimed amount of MCC. 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. Mulye teaches microcrystalline cellulose (MCC) enhances the ability to form tablets [0045]. Instant claim 39 is directed to a composition that is a tablet.
One skilled in the art would have been motivated to include microcrystalline cellulose (MCC) in a method of treating insomnia as instantly claimed because MCC enhances the ability to form tablets and improves the physical properties of tablets, capsules, powders and microgranules as disclosed by the cited prior art references. Adjusting the amount of MCC would achieve the desired physical properties of the tablets. Thus, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to provide a method of treating insomnia as instantly claimed in view of the teachings of Kavey, Rogowski, and Mulye, as a whole.
The combination of prior art cited makes obvious all the structural limitations of the claims and the performance of the claimed method of treating insomnia, therefore, the dosage of doxepin and the dosage amounts of doxepin as taught by the cited prior art are expected to have the same properties, absent factual evidence to the contrary.
Accordingly, it would have been obvious for one of ordinary skill in the art to provide a method of treating chronic and non-chronic forms of insomnia and patients suffering from difficulties in sleep onset and sleep maintenance wherein doxepin plasma concentration is about 0.1 ng/ml doxepin within about 60 minutes by administering 1-6 mg of doxepin as taught by Kavey Rogowski and Mulye, as a whole, having a reasonable expectation of success.
Regarding claims 24 and 39,
The teachings of Kave, Rogowski, and Mulye, as a whole, are described above.
Further, Rogowski teaches the composition in the form of tablets contain a lubricate such as magnesium stearate [0079].
Thus, it would have been prima facie obvious to one of ordinary skill in the art to provide doxepin in a dosage form that is a tablet wherein the tablet comprises a lubricant that is magnesium stearate.
Regarding claim 30,
The teachings of Kavey, Rogowski and Mulye, as a whole, are described above.
The pharmaceutical composition comprising doxepin as taught by Kavey, Rogowski and Mulye, as a whole, would be indistinguishable from the claimed composition, where there is no unobvious distinction between the structural and functional characteristics of the claimed composition and the composition of the prior art, so that the composition as taught by the cited prior art would necessarily provide a composition that has a composition that provides at least an 85 percent release of doxepin within 30 minutes using U.S. Pharmacopeia (USP) Apparatus I at 100 rpm (or Apparatus II at 50 rpm) in 0.1 N HCI or Simulated Gastric Fluid USP without enzymes. This property or properties would be the natural result of the combination of the prior art elements. Inherency is appropriate in an obviousness analysis "when the limitation at issue is the 'natural result' of the combination of prior art elements." PAR Pharm., Inc. v.TWI Pharms., Inc., 773 F.3d 1186, 1195 (Fed. Cir. 2014) (quoting In re Oelrich, 666 F.2d 578,581 (CCPA 1981)). Lack of recognition of the inherency by those skilled in the art is thus not dispositive.
Regarding claims 36-38,
The teachings of Kavey, Rogowski and Mulye, as a whole, are described above. For instance, Kavey teaches a method for treating chronic and non-chronic forms of insomnia comprising administration of doxepin, or pharmaceutically acceptable forms of doxepin and Rogowski teaches the methods described herein can be used to treat individuals suffering from a sleep disorder, such as insomnia. The individual can suffer from a chronic insomnia or a non-chronic insonmia. For chronic (e.g., greater than 3-4weeks) or non-chronic insonmias, a patient may suffer from difficulties in sleep onset, sleep maintenance (interruption of sleep during the night by periods of wakefulness), sleep duration, sleep efficiency, premature early-morning awakening, short term insomnia or a transient insomnia or a combination thereof.
Regarding claim 41.
Mulye teaches the pharmaceutical composition of the present invention are compressed into a tablet, the hardness of the tablet is 5-25 kp and more preferably 8-20 Kp ([0045]; [0067]; [0071]) of which 5-25 Kp and 8-20 Kp overlap with the claimed amount of a hardness value of at least 2 Kp, as claimed in claim 41. 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).
Regarding claim 42.
Mulye teaches that the tablets prepared in accordance with the present invention are hard and dense, have low friability and provide controlled and sustained release over an extended period. Moreover, Mulye teaches that as a result of the process described herein, a tablet product is obtained which has the desired hardness and friability typically found for pharmaceutical tablets.
Thus, there is no unobvious distinction between the structural and functional characteristics of the claimed composition and the composition of the prior art, therefore, it would necessarily follow that the composition as taught Kavey, Rogowski and Mulye, as a whole, would provide a composition that comprises a friability value of 1% or less. This property or properties would be the natural result of the combination of the prior art elements. Inherency is appropriate in an obviousness analysis "when the limitation at issue is the 'natural result' of the combination of prior art elements." PAR Pharm. Moreover, as evidenced by the Specification at para. [0214]: Instant Specification states that formulations having low friability and a hardness values of at least 2 Kp, wherein, e.g., a low friability value is 1% or less.
Accordingly, it would have been prima facie obvious to provide a pharmaceutical composition comprising doxepin in accordance with the teachings of Kavey, Rogowski and Mulye, as a whole, in a method of treating insomnia, the method comprising treating a patient that suffers from difficulties in sleep duration, a patient that suffers from difficulties in sleep efficiency and a patient that suffers from difficulties in premature early-morning awakening, having a reasonable expectation of success.
All the claimed elements herein are known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
Thus, it would have been obvious for one of ordinary skill in the art to provide instantly claimed invention and one of ordinary skill would have had a reasonable expectation of success in producing the claimed invention. Therefore, in the absence of evidence to the contrary, the invention as a whole would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by Kavey, Rogowski and Mulye, and Instant Specification.
Response to Arguments
Applicants argue that claim 21 recites that the pharmaceutical composition comprises microcrystalline cellulose, and wherein the amount of microcrystalline cellulose is about 50% w/w to about 80% w/w. Applicant argue that neither Kavey, Rogowski, Mulye and Takeo, disclose such a pharmaceutical composition.
Applicants’ arguments directed to the reference: Takei, are moot because the teachings of Takeo are not provided in the above 103 rejection.
Applicant’s arguments have been fully considered but they are not persuasive, because the teachings of Mulye, as described above, cure the deficiencies regarding the amount of microcrystalline cellulose in the composition. Particularly, Mulye teaches pharmaceutical unit dosage form for administration of medicinal compounds comprising doxepin and excipients comprising microcrystalline cellulose, wherein microcrystalline cellulose is present in formulations from about 5% to about 65% by weight ([0039]; [0045-0046; See entire document), of which the amounts of microcrystalline cellulose (MCC) of about 5-65%wt overlap with the claimed amount of MCC of about 50% w/w to about 80% w/w. 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). Moreover, A prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art." In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003).
Claim 40 is rejected under AIA 35 U.S.C. 103 as being unpatentable over Kavey et al (USP 6211229, of record) [Kavey] in view of Rogowski et al (US 2007/0281990, of record) [Rogowski], Mulye (US 20040224017, of record) [Mulye], as evidenced by Specification as applied to Claims 21, 24-39 and 41-42 above and further in view of Sherwood et al (USP 5,585,115).
The teachings of Kavey, Rogowski and Mulye, and as evidenced by the Instant Specification are fully described above.
The cited prior art references fail to disclose that the composition comprises colloidal silicon dioxide in an amount ranging from about 0.1% to about 1.5% w/w.
However, Sherwood cures the deficiencies.
Sherwood teaches a microcrystalline cellulose-based excipient having improved compressibility, wherein the excipient is an agglomerate of microcrystalline cellulose particles and from about 0.1 % to about 20 % colloidal silicon dioxide particles (Abstract). Further, Sherwood teaches colloidal silicon dioxide particles may be present in about 0.5 % to about 10% w/w (these range amount of colloidal silicon dioxide particles overlap with claimed ranges) (col.5, lns.1-14; ciol.8, lns.21-43; col.10, lns.36-47; col.11, lns.34-46; See entire document). 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). Moreover, A prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art." In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003
Sherwood teaches that the novel excipient of the invention utilizes a colloidal silicon dioxide, it has been found that the resultant excipient product surprisingly provides a compressibility which is substantially improved (col.9, lns.1-8; See entire document).
It would have been well within the purview of one of ordinary skill in art to optimize the amount of colloidal silicon dioxide to best provide a formulation comprising improved compressibility, i.e., within the range as taught by Sherwood, having a reasonable expectation of success.
The optimization of known effective amounts of known excipients to be provided in composition to improve compressibility of a tablet thereof, is considered well in the competence level of an ordinary skilled artisan in pharmaceutical science, involving merely routine skill in the art. It has been held that it is within the skill in the art to select optimal parameters in a composition in order to achieve a beneficial effect. See In re Boesch, 205 USPQ 215 (CCPA 1980).
Optimization of parameters is a routine practice that would be obvious to a person of ordinary skill in the art to employ and reasonably expect success. See In re Aller, 220 F.2d 454, 456, 105 USPQ 233,235 (CCPA 1955) & MPEP 2144.05.
Thus, it would have been obvious to the modify the composition as taught by Kavey, Rogowski and Mulye in view of the teachings of Sherwood order to substantially improve the compressibility of the composition in the form of a tablet having a reasonable expectation of success.
New Grounds of Rejection
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 conflicting claims 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) 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 www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 21 and 24-42 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4-9 and 11-20 of U.S. Patent No. 11096920 (herein ‘920) in view of Mulye (US 20040224017, of record) and Sherwood et al (USP 5,585,115).
Although the claims at issue are not identical, they are not patentably distinct from each other because the subject matter claimed in the Instant Application would have been prima facie obvious to one of ordinary skill at the time of the invention.
Instant Claims are directed to a method of treating insomnia, the method comprising administering to a patient in need thereof a pharmaceutical composition comprising about 0.5 to about 7 mg of doxepin, or a pharmaceutically acceptable salt thereof, wherein administering the composition provides a plasma concentration of at least 0.1 ng/mL doxepin within a time frame of not more than about 60 minutes; wherein the pharmaceutical composition comprises microcrystalline cellulose, wherein the amount of microcrystalline cellulose is about 20% to about 80% w/w, wherein the composition further comprises magnesium stearate; wherein the insomnia is a chronic insomnia; a non-chronic insomnia, a non-chronic insomnia; wherein the patient suffers from difficulties in sleep onset, sleep maintenance, sleep duration, sleep efficiency and from difficulties in premature early-morning awakening; wherein the composition comprises a tablet.
‘920 claims are directed to a method of treating insomnia, the method comprises administering to a patient in need thereof a pharmaceutical composition comprising about 0.5 to about 7 mg of doxepin, or a pharmaceutically acceptable salt thereof, and about 80% (overlaps with Instant Claims ) to about 99.8% w/w silicified microcrystalline cellulose; wherein administering the composition provides a plasma concentration of at least 0.05 ng/mL doxepin within a time frame of not more than about 90 minutes (overlaps with Instant Claims), wherein the composition further comprises about 0.25 to about 1.5% w/w magnesium stearate; wherein the composition comprises about 6 mg of doxepin or a pharmaceutically acceptable salt thereof; wherein the insomnia is a chronic insomnia; a non-chronic insomnia, a non-chronic insomnia; wherein the patient suffers from difficulties in sleep onset, sleep maintenance, sleep duration, sleep efficiency and from difficulties in premature early-morning awakening; wherein the composition comprises a tablet; wherein administering the composition provides a plasma concentration of at least 0.1 ng/mL doxepin within a time frame of not more than about 60 minutes (over laps with Instant Claims). 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.
Instant Claims and ‘920 claims are both directed to a method of treating insomnia, wherein the insomnia that is a chronic insomnia; a non-chronic insomnia, a non-chronic insomnia; and, wherein the patient suffers from difficulties in sleep onset, sleep maintenance, sleep duration, sleep efficiency and from difficulties in premature early-morning awakening.
‘920 claims differ from Instant claims in that the ‘920 claims recited that the pharmaceutical composition comprises silicified microcrystalline cellulose and ‘920 claims do not recite the pharmaceutical composition comprises microcrystalline cellulose, wherein the amount of microcrystalline cellulose is about 50% to about 80%, and that the composition comprises colloidal silicon dioxide in an amount ranging from about 0.1 % to about 1.5% w/w (Instant claim 40); the composition comprises a hardness value of at least 2 Kp (Instant claim 41); and the composition comprises a friability value of 1 % or less. (Instant claim 42);
Respectfully, Instant Claims recite the transitional phrase ‘comprising’; the transitional term ‘comprising’ is open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004). Therefore, Instant Claims do not exclude silicified microcrystalline cellulose.
Mulye and Sherwood, as a whole, cure the deficiencies.
Mulye teaches pharmaceutical unit dosage form for administration of medicinal compounds comprising doxepin and excipients comprising microcrystalline cellulose and silicified microcrystalline cellulose. In particular, Mulye teaches that silicified microcrystalline cellulose is highly compressible co-processed combination of microcrystalline cellulose with colloidal silicon dioxide, which is used to solve tableting problems [0018]; [0029]; [0039]; [0045]; claims 2-4; 46-48). One skilled in the art would have been motivated to use silicified microcrystalline cellulose in Instant Claims in a tablet comprising doxepin because silicified microcrystalline cellulose has superior tableting characteristics, wherein silicified microcrystalline cellulose speeds the release of a medicament in a pharmaceutical composition as taught by Mulye [0018]. Furthermore, Mulye teaches pharmaceutical unit dosage form for administration of medicinal compounds comprising doxepin and excipients comprising microcrystalline cellulose, wherein microcrystalline cellulose is present in formulations from about 5% to about 65% by weight ([0039]; [0045-0046; See entire document), of which the amounts of microcrystalline cellulose (MCC) of about 5-65%wt overlap with the claimed amount of MCC. 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. Mulye teaches microcrystalline cellulose (MCC) enhances the ability to form tablets [0045]. Instant claim 39 is directed to a composition that is a tablet.
Regarding claim 41,
Mulye teaches the pharmaceutical composition of the present invention are compressed into a tablet, the hardness of the tablet is 5-25 kp and more preferably 8-20 Kp ([0045]; [0067]; [0071]) of which 5-25 Kp and 8-20 Kp overlap with the claimed amount of a hardness value of at least 2 Kp, as claimed in claim 41. 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).
Regarding claim 42,
Mulye teaches that the tablets prepared in accordance with the present invention are hard and dense, have low friability and provide controlled and sustained release over an extended period. Moreover, Mulye teaches that as a result of the process described herein, a tablet product is obtained which has the desired hardness and friability typically found for pharmaceutical tablets. Thus, there is no unobvious distinction between the structural and functional characteristics of the claimed composition and the composition of the prior art, therefore, it would necessarily follow that the composition as taught Kavey, Rogowski and Mulye, as a whole, would provide a composition that comprises a friability value of 1% or less. This property or properties would be the natural result of the combination of the prior art elements. Inherency is appropriate in an obviousness analysis "when the limitation at issue is the 'natural result' of the combination of prior art elements." PAR Pharm.
Regarding claim 40,
Sherwood teaches a microcrystalline cellulose-based excipient having improved compressibility, wherein the excipient is an agglomerate of microcrystalline cellulose particles and from about 0.1 % to about 20 % colloidal silicon dioxide particles (Abstract). Further, Sherwood teaches colloidal silicon dioxide particles may be present in about 0.5 % to about 10% w/w (these range amount of colloidal silicon dioxide particles overlap with claimed ranges) (col.5, lns.1-14; ciol.8, lns.21-43; col.10, lns.36-47; col.11, lns.34-46; See entire document). 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). Moreover, A prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art." In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003
Sherwood teaches that the novel excipient of the invention utilizes a colloidal silicon dioxide, it has been found that the resultant excipient product surprisingly provides a compressibility which is substantially improved (col.9, lns.1-8; See entire document).
Thus, it would have been obvious to the modify the composition as taught by Kavey, Rogowski and Mulye in view of the teachings of Sherwood order to substantially improve the compressibility of the composition in the form of a tablet having a reasonable expectation of success.
Regarding claim 41.
Mulye teaches the pharmaceutical composition of the present invention are compressed into a tablet, the hardness of the tablet is 5-25 kp and more preferably 8-20 Kp ([0045]; [0067]; [0071]) of which 5-25 Kp and 8-20 Kp overlap with the claimed amount of a hardness value of at least 2 Kp, as claimed in claim 41. 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).
Regarding claim 42.
Mulye teaches that the tablets prepared in accordance with the present invention are hard and dense, have low friability and provide controlled and sustained release over an extended period. Moreover, Mulye teaches that as a result of the process described herein, a tablet product is obtained which has the desired hardness and friability typically found for pharmaceutical tablets.
Thus, there is no unobvious distinction between the structural and functional characteristics of the claimed composition and the composition of the prior art, therefore, it would necessarily follow that the composition as taught Kavey, Rogowski and Mulye, as a whole, would provide a composition that comprises a friability value of 1% or less. This property or properties would be the natural result of the combination of the prior art elements. Inherency is appropriate in an obviousness analysis "when the limitation at issue is the 'natural result' of the combination of prior art elements." PAR Pharm.,
Thus, Instant claims and the ‘920 claims in view of Mulye and Sherwood, as a whole, are obviously directed to common subject matter; therefore, the subject matter in Instant Claims would have been prima facie obvious to provide before the effective date of at the time of invention, absence evidence to the contrary.
Claims 21 and 24-42 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10548871 (herein ‘871) in view of Mulye (US 20040224017, of record).
Although the claims at issue are not identical, they are not patentably distinct from each other because the subject matter claimed in the Instant Application would have been prima facie obvious to one of ordinary skill at the time of the invention.
Instant Claims are directed to a method of treating insomnia, the method comprising administering to a patient in need thereof a pharmaceutical composition comprising about 0.5 to about 7 mg of doxepin, or a pharmaceutically acceptable salt thereof, wherein administering the composition provides a plasma concentration of at least 0.1 ng/mL doxepin within a time frame of not more than about 60 minutes; wherein the pharmaceutical composition comprises microcrystalline cellulose, wherein the amount of microcrystalline cellulose is about 20% to about 80% w/w, wherein the composition further comprises magnesium stearate; wherein the insomnia is a chronic insomnia; a non-chronic insomnia, a non-chronic insomnia; wherein the patient suffers from difficulties in sleep onset, sleep maintenance, sleep duration, sleep efficiency and from difficulties in premature early-morning awakening; wherein the composition comprises a tablet.
‘871 claims are directed to a method of treating insomnia, the method comprises administering to a patient in need thereof a pharmaceutical composition comprising about 0.5 to about 7 mg of doxepin, or a pharmaceutically acceptable salt thereof, and about 80% (overlaps with Instant Claims ) to about 99.8% w/w silicified microcrystalline cellulose; wherein administering the composition provides a plasma concentration of at least 0.05 ng/mL doxepin within a time frame of not more than about 90 minutes (overlaps with Instant Claims), wherein the composition further comprises about 0.25 to about 1.5% w/w magnesium stearate; wherein the composition comprises about 6 mg of doxepin or a pharmaceutically acceptable salt thereof; wherein the insomnia is a chronic insomnia; a non-chronic insomnia, a non-chronic insomnia; wherein the patient suffers from difficulties in sleep onset, sleep maintenance, sleep duration, sleep efficiency and from difficulties in premature early-morning awakening; wherein the composition comprises a tablet; wherein administering the composition provides a plasma concentration of at least 0.1 ng/mL doxepin within a time frame of not more than about 60 minutes (over laps with Instant Claims).
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.
‘871 claims differ from Instant claims in that the ‘920 claims recited that the pharmaceutical composition comprises silicified microcrystalline cellulose and ‘920 claims do not recite the pharmaceutical composition comprises microcrystalline cellulose, wherein the amount of microcrystalline cellulose is about 50% to about 80%, and that the composition comprises colloidal silicon dioxide in an amount ranging from about 0.1 % to about 1.5% w/w (Instant claim 40); the composition comprises a hardness value of at least 2 Kp (Instant claim 41); and the composition comprises a friability value of 1 % or less. (Instant claim 42);
Respectfully, Instant Claims recite the transitional phrase ‘comprising’; the transitional term ‘comprising’ is open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004). Therefore, Instant Claims do not exclude silicified microcrystalline cellulose.
Mulye and Sherwood, as a whole, cure the deficiencies.
Mulye teaches pharmaceutical unit dosage form for administration of medicinal compounds comprising doxepin and excipients comprising microcrystalline cellulose and silicified microcrystalline cellulose. In particular, Mulye teaches that silicified microcrystalline cellulose is highly compressible co-processed combination of microcrystalline cellulose with colloidal silicon dioxide, which is used to solve tableting problems [0018]; [0029]; [0039]; [0045]; claims 2-4; 46-48). One skilled in the art would have been motivated to use silicified microcrystalline cellulose in Instant Claims in a tablet comprising doxepin because silicified microcrystalline cellulose has superior tableting characteristics, wherein silicified microcrystalline cellulose speeds the release of a medicament in a pharmaceutical composition as taught by Mulye [0018]. Furthermore, Mulye teaches pharmaceutical unit dosage form for administration of medicinal compounds comprising doxepin and excipients comprising microcrystalline cellulose, wherein microcrystalline cellulose is present in formulations from about 5% to about 65% by weight ([0039]; [0045-0046; See entire document), of which the amounts of microcrystalline cellulose (MCC) of about 5-65%wt overlap with the claimed amount of MCC. 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. Mulye teaches microcrystalline cellulose (MCC) enhances the ability to form tablets [0045]. Instant claim 39 is directed to a composition that is a tablet.
Regarding claim 41,
Mulye teaches the pharmaceutical composition of the present invention are compressed into a tablet, the hardness of the tablet is 5-25 kp and more preferably 8-20 Kp ([0045]; [0067]; [0071]) of which 5-25 Kp and 8-20 Kp overlap with the claimed amount of a hardness value of at least 2 Kp, as claimed in claim 41. 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).
Regarding claim 42,
Mulye teaches that the tablets prepared in accordance with the present invention are hard and dense, have low friability and provide controlled and sustained release over an extended period. Moreover, Mulye teaches that as a result of the process described herein, a tablet product is obtained which has the desired hardness and friability typically found for pharmaceutical tablets. Thus, there is no unobvious distinction between the structural and functional characteristics of the claimed composition and the composition of the prior art, therefore, it would necessarily follow that the composition as taught Kavey, Rogowski and Mulye, as a whole, would provide a composition that comprises a friability value of 1% or less. This property or properties would be the natural result of the combination of the prior art elements. Inherency is appropriate in an obviousness analysis "when the limitation at issue is the 'natural result' of the combination of prior art elements." PAR Pharm.
Regarding claim 40,
Sherwood teaches a microcrystalline cellulose-based excipient having improved compressibility, wherein the excipient is an agglomerate of microcrystalline cellulose particles and from about 0.1 % to about 20 % colloidal silicon dioxide particles (Abstract). Further, Sherwood teaches colloidal silicon dioxide particles may be present in about 0.5 % to about 10% w/w (these range amount of colloidal silicon dioxide particles overlap with claimed ranges) (col.5, lns.1-14; ciol.8, lns.21-43; col.10, lns.36-47; col.11, lns.34-46; See entire document). 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). Moreover, A prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art." In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003
Sherwood teaches that the novel excipient of the invention utilizes a colloidal silicon dioxide, it has been found that the resultant excipient product surprisingly provides a compressibility which is substantially improved (col.9, lns.1-8; See entire document).
Thus, it would have been obvious to the modify the composition as taught by Kavey, Rogowski and Mulye in view of the teachings of Sherwood order to substantially improve the compressibility of the composition in the form of a tablet having a reasonable expectation of success.
Regarding claim 41.
Mulye teaches the pharmaceutical composition of the present invention are compressed into a tablet, the hardness of the tablet is 5-25 kp and more preferably 8-20 Kp ([0045]; [0067]; [0071]) of which 5-25 Kp and 8-20 Kp overlap with the claimed amount of a hardness value of at least 2 Kp, as claimed in claim 41. 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).
Regarding claim 42.
Mulye teaches that the tablets prepared in accordance with the present invention are hard and dense, have low friability and provide controlled and sustained release over an extended period. Moreover, Mulye teaches that as a result of the process described herein, a tablet product is obtained which has the desired hardness and friability typically found for pharmaceutical tablets.
Thus, there is no unobvious distinction between the structural and functional characteristics of the claimed composition and the composition of the prior art, therefore, it would necessarily follow that the composition as taught Kavey, Rogowski and Mulye, as a whole, would provide a composition that comprises a friability value of 1% or less. This property or properties would be the natural result of the combination of the prior art elements. Inherency is appropriate in an obviousness analysis "when the limitation at issue is the 'natural result' of the combination of prior art elements." PAR Pharm.,
Thus, Instant claims and the ‘871 claims in view of Mulye and Sherwood, as a whole, are obviously directed to common subject matter; therefore, the subject matter in Instant Claims would have been prima facie obvious to provide before the effective date of at the time of invention, absence evidence to the contrary.
Claims 21 and 24-42 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4-13 and 14-20 of U.S. Patent No. 9907780 (herein ‘780) in view of Mulye (US 20040224017, of record) and Sherwood et al (USP 5,585,115).
Although the claims at issue are not identical, they are not patentably distinct from each other because the subject matter claimed in the Instant Application would have been prima facie obvious to one of ordinary skill at the time of the invention.
Instant Claims are directed to a method of treating insomnia, the method comprising administering to a patient in need thereof a pharmaceutical composition comprising about 0.5 to about 7 mg of doxepin, or a pharmaceutically acceptable salt thereof, wherein administering the composition provides a plasma concentration of at least 0.1 ng/mL doxepin within a time frame of not more than about 60 minutes; wherein the pharmaceutical composition comprises microcrystalline cellulose, wherein the amount of microcrystalline cellulose is about 20% to about 80% w/w, wherein the composition further comprises magnesium stearate; wherein the insomnia is a chronic insomnia; a non-chronic insomnia, a non-chronic insomnia; wherein the patient suffers from difficulties in sleep onset, sleep maintenance, sleep duration, sleep efficiency and from difficulties in premature early-morning awakening; wherein the composition comprises a tablet.
‘780 claims are directed to a pharmaceutical composition comprising about 0.5 to about 7 mg of doxepin (overlaps with Instant Claims), or a pharmaceutically acceptable salt thereof, and about 92% to about 99.8% w/w silicified microcrystalline cellulose; wherein the pharmaceutical composition has dissolution and bioavailability characteristics such that after administration to a 70 kg human, the composition provides a plasma concentration of at least 0.05 ng/mL doxepin within a time frame of not more than about 90 minutes (overlaps with Instant claims); wherein the composition further comprises about 0.25 to about 1.5% w/w magnesium stearate; A pharmaceutical composition comprising about 0.5 to about 7 mg of doxepin, or a pharmaceutically acceptable salt thereof, and about 92% to about 99.8% w/w silicified microcrystalline cellulose, wherein the pharmaceutical composition has dissolution and bioavailability characteristics such that after administration to a 70 kg human, the composition provides a plasma concentration of at least 0.1 ng/mL doxepin within a time frame of not more than about 60 minutes (overlaps with Instant claims); wherein the time frame to provide a plasma concentration of at least 0.1 ng/mL is not more than about 50 minutes; wherein the composition comprises about 94% to about 98.5% w/w silicified microcrystalline cellulose; A pharmaceutical composition comprising about 2.5 to about 7 mg of doxepin, or a pharmaceutically acceptable salt thereof, and about 94% to about 98.5% w/w silicified microcrystalline cellulose, wherein the pharmaceutical composition has dissolution and bioavailability characteristics such that after administration to a 70 kg human, the composition provides a plasma concentration of at least 0.1 ng/mL doxepin within a time frame of not more than about 60 minutes (overlaps with Instant claims).
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.
‘780 claims differ from Instant claims in that the ‘920 claims recited that the pharmaceutical composition comprises silicified microcrystalline cellulose and ‘920 claims do not recite the pharmaceutical composition comprises microcrystalline cellulose, wherein the amount of microcrystalline cellulose is about 50% to about 80%, and that the composition comprises colloidal silicon dioxide in an amount ranging from about 0.1 % to about 1.5% w/w (Instant claim 40); the composition comprises a hardness value of at least 2 Kp (Instant claim 41); and the composition comprises a friability value of 1 % or less. (Instant claim 42);
Respectfully, Instant Claims recite the transitional phrase ‘comprising’; the transitional term ‘comprising’ is open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004). Therefore, Instant Claims do not exclude silicified microcrystalline cellulose.
Mulye and Sherwood, as a whole, cure the deficiencies.
Mulye teaches pharmaceutical unit dosage form for administration of medicinal compounds comprising doxepin and excipients comprising microcrystalline cellulose and silicified microcrystalline cellulose. In particular, Mulye teaches that silicified microcrystalline cellulose is highly compressible co-processed combination of microcrystalline cellulose with colloidal silicon dioxide, which is used to solve tableting problems [0018]; [0029]; [0039]; [0045]; claims 2-4; 46-48). One skilled in the art would have been motivated to use silicified microcrystalline cellulose in Instant Claims in a tablet comprising doxepin because silicified microcrystalline cellulose has superior tableting characteristics, wherein silicified microcrystalline cellulose speeds the release of a medicament in a pharmaceutical composition as taught by Mulye [0018]. Furthermore, Mulye teaches pharmaceutical unit dosage form for administration of medicinal compounds comprising doxepin and excipients comprising microcrystalline cellulose, wherein microcrystalline cellulose is present in formulations from about 5% to about 65% by weight ([0039]; [0045-0046; See entire document), of which the amounts of microcrystalline cellulose (MCC) of about 5-65%wt overlap with the claimed amount of MCC. 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. Mulye teaches microcrystalline cellulose (MCC) enhances the ability to form tablets [0045]. Instant claim 39 is directed to a composition that is a tablet.
Regarding claim 41,
Mulye teaches the pharmaceutical composition of the present invention are compressed into a tablet, the hardness of the tablet is 5-25 kp and more preferably 8-20 Kp ([0045]; [0067]; [0071]) of which 5-25 Kp and 8-20 Kp overlap with the claimed amount of a hardness value of at least 2 Kp, as claimed in claim 41. 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).
Regarding claim 42,
Mulye teaches that the tablets prepared in accordance with the present invention are hard and dense, have low friability and provide controlled and sustained release over an extended period. Moreover, Mulye teaches that as a result of the process described herein, a tablet product is obtained which has the desired hardness and friability typically found for pharmaceutical tablets. Thus, there is no unobvious distinction between the structural and functional characteristics of the claimed composition and the composition of the prior art, therefore, it would necessarily follow that the composition as taught Kavey, Rogowski and Mulye, as a whole, would provide a composition that comprises a friability value of 1% or less. This property or properties would be the natural result of the combination of the prior art elements. Inherency is appropriate in an obviousness analysis "when the limitation at issue is the 'natural result' of the combination of prior art elements." PAR Pharm.
Regarding claim 40,
Sherwood teaches a microcrystalline cellulose-based excipient having improved compressibility, wherein the excipient is an agglomerate of microcrystalline cellulose particles and from about 0.1 % to about 20 % colloidal silicon dioxide particles (Abstract). Further, Sherwood teaches colloidal silicon dioxide particles may be present in about 0.5 % to about 10% w/w (these range amount of colloidal silicon dioxide particles overlap with claimed ranges) (col.5, lns.1-14; ciol.8, lns.21-43; col.10, lns.36-47; col.11, lns.34-46; See entire document). 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). Moreover, A prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art." In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003
Sherwood teaches that the novel excipient of the invention utilizes a colloidal silicon dioxide, it has been found that the resultant excipient product surprisingly provides a compressibility which is substantially improved (col.9, lns.1-8; See entire document).
Thus, it would have been obvious to the modify the composition as taught by Kavey, Rogowski and Mulye in view of the teachings of Sherwood order to substantially improve the compressibility of the composition in the form of a tablet having a reasonable expectation of success.
Regarding claim 41.
Mulye teaches the pharmaceutical composition of the present invention are compressed into a tablet, the hardness of the tablet is 5-25 kp and more preferably 8-20 Kp ([0045]; [0067]; [0071]) of which 5-25 Kp and 8-20 Kp overlap with the claimed amount of a hardness value of at least 2 Kp, as claimed in claim 41. 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).
Regarding claim 42.
Mulye teaches that the tablets prepared in accordance with the present invention are hard and dense, have low friability and provide controlled and sustained release over an extended period. Moreover, Mulye teaches that as a result of the process described herein, a tablet product is obtained which has the desired hardness and friability typically found for pharmaceutical tablets.
Thus, there is no unobvious distinction between the structural and functional characteristics of the claimed composition and the composition of the prior art, therefore, it would necessarily follow that the composition as taught Kavey, Rogowski and Mulye, as a whole, would provide a composition that comprises a friability value of 1% or less. This property or properties would be the natural result of the combination of the prior art elements. Inherency is appropriate in an obviousness analysis "when the limitation at issue is the 'natural result' of the combination of prior art elements." PAR Pharm.,
Thus, Instant claims and the ‘780 claims in view of Mulye and Sherwood, as a whole, are obviously directed to common subject matter; therefore, the subject matter in Instant Claims would have been prima facie obvious to provide before the effective date of at the time of invention, absence evidence to the contrary.
Claims 21 and 24-42 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 9532971 (herein ‘971) in view of Mulye (US 20040224017, of record) and Sherwood et al (USP 5,585,115).
Although the claims at issue are not identical, they are not patentably distinct from each other because the subject matter claimed in the Instant Application would have been prima facie obvious to one of ordinary skill at the time of the invention.
Instant Claims are directed to a method of treating insomnia, the method comprising administering to a patient in need thereof a pharmaceutical composition comprising about 0.5 to about 7 mg of doxepin, or a pharmaceutically acceptable salt thereof, wherein administering the composition provides a plasma concentration of at least 0.1 ng/mL doxepin within a time frame of not more than about 60 minutes; wherein the pharmaceutical composition comprises microcrystalline cellulose, wherein the amount of microcrystalline cellulose is about 20% to about 80% w/w, wherein the composition further comprises magnesium stearate; wherein the insomnia is a chronic insomnia; a non-chronic insomnia, a non-chronic insomnia; wherein the patient suffers from difficulties in sleep onset, sleep maintenance, sleep duration, sleep efficiency and from difficulties in premature early-morning awakening; wherein the composition comprises a tablet.
‘971 claims are directed to a pharmaceutical composition comprising from about 0.5 to about 7 mg of doxepin (overlaps with Instant claims), or a pharmaceutically acceptable salt thereof, and from about 92% to about 99.8% w/w silicified microcrystalline cellulose, the composition having one or more of the characteristics selected from the group consisting of: a hardness value of at least 2 Kp, a friability value of 1% or less, a disintegration time of about 1 minute as per USP protocols (, at least an 80% release of doxepin within 15 minutes using compendial method for measuring dissolution of doxepin, at least an 85 percent release of doxepin within 30 minutes using U.S. Pharmacopeia (USP) Apparatus I at 100 rpm (or Apparatus II at 50 rpm) in 0.1 N HCl or Simulated Gastric Fluid USP without enzymes, at least an 85 percent release of doxepin within 30 minutes using U.S. Pharmacopeia (USP) Apparatus I at 100 rpm (or Apparatus II at 50 rpm) in a pH 4.5 buffer, and at least an 85 percent release of doxepin within 30 minutes using U.S. Pharmacopeia (USP) Apparatus I at 100 rpm (or Apparatus II at 50 rpm) in a pH 6.8 buffer or Simulated Intestinal Fluid USP without enzymes; and wherein the pharmaceutical composition has dissolution and bioavailability characteristics such that after administration to a 70 kg human, the composition provides a plasma concentration of at least 0.05 ng/m doxepin within a time frame of not more than about 90 minutes (overlaps with Instant claims, where there is no unobvious distinction between the structural and functional characteristics of the claimed composition and the composition of the prior art); further comprising colloidal silicon dioxide and magnesium stearate; A pharmaceutical unit dosage form, comprising: doxepin or a pharmaceutically-acceptable salt thereof in an amount equivalent to about 3 or 6 mg doxepin hydrochloride (i.e., a pharmaceutically acceptable salt); one or more pharmaceutically-acceptable excipients; and optionally, a capsule or coating; wherein the excipients and any capsule or coating are selected to provide a swallowable unit dosage that is at least externally solid and that has dissolution and bioavailability characteristics such that after administration to a 70 kg human, the dosage form provides a plasma concentration of at least 0.1 ng/mL doxepin within a time frame of not more than about 60 minutes (overlaps with Instant claims); and wherein the unit dosage form comprises about 92% to about 99.8% w/w silicified microcrystalline cellulose; wherein the time frame to provide a plasma concentration of at least 0.1 ng/mL is not more than about 50 minutes; wherein the doxepin or the pharmaceutically-acceptable salt thereof is in an amount equivalent to about 3 mg doxepin hydrochloride; and wherein the doxepin or the pharmaceutically-acceptable salt thereof is in an amount equivalent to about 6 mg doxepin hydrochloride (overlaps with Instant Claims).
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.
‘971 claims differ from Instant claims in that the ‘920 claims recited that the pharmaceutical composition comprises silicified microcrystalline cellulose and ‘920 claims do not recite the pharmaceutical composition comprises microcrystalline cellulose, wherein the amount of microcrystalline cellulose is about 50% to about 80%, and that the composition comprises colloidal silicon dioxide in an amount ranging from about 0.1 % to about 1.5% w/w (Instant claim 40); the composition comprises a hardness value of at least 2 Kp (Instant claim 41); and the composition comprises a friability value of 1 % or less. (Instant claim 42);
Respectfully, Instant Claims recite the transitional phrase ‘comprising’; the transitional term ‘comprising’ is open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004). Therefore, Instant Claims do not exclude silicified microcrystalline cellulose.
Mulye and Sherwood, as a whole, cure the deficiencies.
Mulye teaches pharmaceutical unit dosage form for administration of medicinal compounds comprising doxepin and excipients comprising microcrystalline cellulose and silicified microcrystalline cellulose. In particular, Mulye teaches that silicified microcrystalline cellulose is highly compressible co-processed combination of microcrystalline cellulose with colloidal silicon dioxide, which is used to solve tableting problems [0018]; [0029]; [0039]; [0045]; claims 2-4; 46-48). One skilled in the art would have been motivated to use silicified microcrystalline cellulose in Instant Claims in a tablet comprising doxepin because silicified microcrystalline cellulose has superior tableting characteristics, wherein silicified microcrystalline cellulose speeds the release of a medicament in a pharmaceutical composition as taught by Mulye [0018]. Furthermore, Mulye teaches pharmaceutical unit dosage form for administration of medicinal compounds comprising doxepin and excipients comprising microcrystalline cellulose, wherein microcrystalline cellulose is present in formulations from about 5% to about 65% by weight ([0039]; [0045-0046; See entire document), of which the amounts of microcrystalline cellulose (MCC) of about 5-65%wt overlap with the claimed amount of MCC. 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. Mulye teaches microcrystalline cellulose (MCC) enhances the ability to form tablets [0045]. Instant claim 39 is directed to a composition that is a tablet.
Regarding claim 41,
Mulye teaches the pharmaceutical composition of the present invention are compressed into a tablet, the hardness of the tablet is 5-25 kp and more preferably 8-20 Kp ([0045]; [0067]; [0071]) of which 5-25 Kp and 8-20 Kp overlap with the claimed amount of a hardness value of at least 2 Kp, as claimed in claim 41. 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).
Regarding claim 42,
Mulye teaches that the tablets prepared in accordance with the present invention are hard and dense, have low friability and provide controlled and sustained release over an extended period. Moreover, Mulye teaches that as a result of the process described herein, a tablet product is obtained which has the desired hardness and friability typically found for pharmaceutical tablets. Thus, there is no unobvious distinction between the structural and functional characteristics of the claimed composition and the composition of the prior art, therefore, it would necessarily follow that the composition as taught Kavey, Rogowski and Mulye, as a whole, would provide a composition that comprises a friability value of 1% or less. This property or properties would be the natural result of the combination of the prior art elements. Inherency is appropriate in an obviousness analysis "when the limitation at issue is the 'natural result' of the combination of prior art elements." PAR Pharm.
Regarding claim 40,
Sherwood teaches a microcrystalline cellulose-based excipient having improved compressibility, wherein the excipient is an agglomerate of microcrystalline cellulose particles and from about 0.1 % to about 20 % colloidal silicon dioxide particles (Abstract). Further, Sherwood teaches colloidal silicon dioxide particles may be present in about 0.5 % to about 10% w/w (these range amount of colloidal silicon dioxide particles overlap with claimed ranges) (col.5, lns.1-14; ciol.8, lns.21-43; col.10, lns.36-47; col.11, lns.34-46; See entire document). 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). Moreover, A prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art." In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003
Sherwood teaches that the novel excipient of the invention utilizes a colloidal silicon dioxide, it has been found that the resultant excipient product surprisingly provides a compressibility which is substantially improved (col.9, lns.1-8; See entire document).
Thus, it would have been obvious to the modify the composition as taught by Kavey, Rogowski and Mulye in view of the teachings of Sherwood order to substantially improve the compressibility of the composition in the form of a tablet having a reasonable expectation of success.
Regarding claim 41.
Mulye teaches the pharmaceutical composition of the present invention are compressed into a tablet, the hardness of the tablet is 5-25 kp and more preferably 8-20 Kp ([0045]; [0067]; [0071]) of which 5-25 Kp and 8-20 Kp overlap with the claimed amount of a hardness value of at least 2 Kp, as claimed in claim 41. 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).
Regarding claim 42.
Mulye teaches that the tablets prepared in accordance with the present invention are hard and dense, have low friability and provide controlled and sustained release over an extended period. Moreover, Mulye teaches that as a result of the process described herein, a tablet product is obtained which has the desired hardness and friability typically found for pharmaceutical tablets.
Thus, there is no unobvious distinction between the structural and functional characteristics of the claimed composition and the composition of the prior art, therefore, it would necessarily follow that the composition as taught Kavey, Rogowski and Mulye, as a whole, would provide a composition that comprises a friability value of 1% or less. This property or properties would be the natural result of the combination of the prior art elements. Inherency is appropriate in an obviousness analysis "when the limitation at issue is the 'natural result' of the combination of prior art elements." PAR Pharm.,
Thus, Instant claims and the ‘971 claims in view of Mulye and Sherwood, as a whole, are obviously directed to common subject matter; therefore, the subject matter in Instant Claims would have been prima facie obvious to provide before the effective date of at the time of invention, absence evidence to the contrary.
Response to Arguments
Applicants argue that the claims of the reference patents do not recite the claimed amount of microcrystalline cellulose of about 50% w/w to about 80% w/w, and Mulye nor Takeo provide the claimed range.
Applicants arguments directed to the reference: Takei, are moot because the teachings of Takeo are not provided in the above 103 rejection.
Applicant’s arguments have been fully considered but they are not persuasive, because the teachings of Mulye, as described above cure the deficiencies regarding the amount of microcrystalline cellulose in the composition. Particularly, Mulye teaches pharmaceutical unit dosage form for administration of medicinal compounds comprising doxepin and excipients comprising microcrystalline cellulose, wherein microcrystalline cellulose is present in formulations from about 5% to about 65% by weight ([0039]; [0045-0046; See entire document), of which the amounts of microcrystalline cellulose (MCC) of about 5-65%wt overlap with the claimed amount of MCC of about 50% w/w to about 80% w/w. 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). Moreover, A prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art." In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003).
Applicant argue that the cited references fail to disclose, teach or suggest the features recited in new claims 40-42.
Applicant’s arguments have been fully considered but they are not persuasive, because, as described above:
Regarding claim 40,
Sherwood teaches a microcrystalline cellulose-based excipient having improved compressibility, wherein the excipient is an agglomerate of microcrystalline cellulose particles and from about 0.1 % to about 20 % colloidal silicon dioxide particles (Abstract). Further, Sherwood teaches colloidal silicon dioxide particles may be present in about 0.5 % to about 10% w/w (these range amount of colloidal silicon dioxide particles overlap with claimed ranges) (col.5, lns.1-14; ciol.8, lns.21-43; col.10, lns.36-47; col.11, lns.34-46; See entire document). 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). Moreover, A prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art." In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003
Sherwood teaches that the novel excipient of the invention utilizes a colloidal silicon dioxide, it has been found that the resultant excipient product surprisingly provides a compressibility which is substantially improved (col.9, lns.1-8; See entire document).
Thus, it would have been obvious to the modify the composition as taught by Kavey, Rogowski and Mulye in view of the teachings of Sherwood order to substantially improve the compressibility of the composition in the form of a tablet having a reasonable expectation of success.
Regarding claim 41.
Mulye teaches the pharmaceutical composition of the present invention are compressed into a tablet, the hardness of the tablet is 5-25 kp and more preferably 8-20 Kp ([0045]; [0067]; [0071]) of which 5-25 Kp and 8-20 Kp overlap with the claimed amount of a hardness value of at least 2 Kp, as claimed in claim 41. 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).
Regarding claim 42.
Mulye teaches that the tablets prepared in accordance with the present invention are hard and dense, have low friability and provide controlled and sustained release over an extended period. Moreover, Mulye teaches that as a result of the process described herein, a tablet product is obtained which has the desired hardness and friability typically found for pharmaceutical tablets.Thus, there is no unobvious distinction between the structural and functional characteristics of the claimed composition and the composition of the prior art, therefore, it would necessarily follow that the composition as taught Kavey, Rogowski and Mulye, as a whole, would provide a composition that comprises a friability value of 1% or less. This property or properties would be the natural result of the combination of the prior art elements. Inherency is appropriate in an obviousness analysis "when the limitation at issue is the 'natural result' of the combination of prior art elements." PAR Pharm.,
Therefore, Instant claims and the Patent Claims ‘920, ‘871, ‘780 and ‘971 in view of Mulye and Sherwood, as a whole, are obviously directed to common subject matter; therefore, the subject matter in Instant Claims would have been prima facie obvious to provide before the effective date of at the time of invention, absence evidence to the contrary.
Conclusions
No claim is allowed.
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/T.W./ Examiner, Art Unit 1619
/SARAH ALAWADI/ Primary Examiner, Art Unit 1619