DETAILED ACTION
Status of the Application
Receipt is acknowledged of Applicants’ Amendments and Remarks, filed 24 October 2025, in the matter of Application N° 18/005,946. Said documents have been entered on the record. The Examiner further acknowledges the following:
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The amendment filed 14 August 2023 canceled claims 4, 12-16, 18, 21, 22, 24-26, and 42-44. No additional claims have been canceled with the present filing. Claims 46-48 are newly added and supported by the originally filed disclosure. See e.g., ¶[0067].
Claims 1, 7, 17, 23, 29, and 30 have been amended. Of particular note is that claim 1 has been amended to incorporate the dosage range of 30-1,800 µg of 25-hydroxyvitamin D from claim 29. The claim has also been amended to recite a new limitation whereby the dosage form releases ≤30% of the 25-hydroxyvitamin D in the formulation within the first two hours of a two-stage dissolution test at pH 1.2. Support for the newly presented property is found, for instance, at ¶[0092].
The lower limit of the range of BHT in the claimed formulation is broadened to 0.01%. Support for the amendment is found in ¶[0076] of the originally-filed disclosure.
The release amount property in claim 23 has been amended such that the dosage releases no more than (NMT) about 7% of the 25-hydroxyvitamin D in the first of the two-stage release property.
Claim 29 has been amended to newly recite that the hard-shell capsule is sealed with a hypromellose (HPMC) sealing solution. Support for the limitation is found in ¶[0031] of the originally-filed disclosure.
No new matter has been added.
Thus, claims 1-3, 5-11, 17, 19, 20, 23, 27-41, and 45-48 now represent all claims currently under consideration.
Information Disclosure Statement
Three new Information Disclosure Statements (IDS), all filed 9 June 2025, are acknowledged and have been considered.
Withdrawn Rejections
Rejection under Statutory Double Patenting
Applicants’ amendment to claim 1 sufficiently overcomes the previously raised rejection. Said rejection is withdrawn.
Rejection under Nonstatutory Double Patenting
Applicants’ amendment to claim 1 overcomes the previously raised rejection. Said rejection is withdrawn and is remade below in view of said amendment (see New Rejections).
Rejection under 35 USC 103
Applicants’ amendments to the previously rejected claims have been fully considered as have been the remarks. Of particular note are Applicants’ addition of newly presented limitations in claims 1 and 29, neither of which were addressed in the previously raised obviousness rejection.
Applicants additionally point out that the rejection appears to be incomplete as neither of the contributions Yamamoto nor Nagahara are discussed and that it includes a claim that was previously canceled (claim 4).
In order to clearly address the most recently presented amendments, the rejection is hereby withdrawn.
New Rejections
Applicants’ amendments and newly filed IDS’s have necessitated the following grounds of rejection:
Nonstatutory 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 1-3, 5-11, 17, 19, 20, 23, 27, 28, 30-41, and 45-48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12, 18, 20-23 and 26-30 of copending Application No. 18/199,117 (reference application) in view of Petkovich et al. (US Pre-Grant Publication Nº 2019/0142747 A1; new IDS reference).
As amended, claim 1 recites a hard shell controlled release dosage form comprising a hard shell capsule containing a solid or semi-solid composition comprising a 25-hydroxyvitamin D compound, the hard shell is a gelatinized hard shell capsule comprising a cellulose ether and a gelatinizing agent; wherein the 25-hydroxyvitamin D compound is provided in an amount in a range of 30 µg to 1800 µg, and the dosage form releases ≤30% of the 25-hydroxyvitamin D in the formulation within the first two hours of a two-stage dissolution test at pH 1.2.
Reference claim 1 discloses the compositional merits of amended claim 1. Reference claim 18 further defines the composition disclosing that the practiced dosage form contains about 0.01% to about 0.03%, or 0.0194% calcifediol. Reference claim 19 discloses that the amount of 25-hydroxyvitamin D compound contained within the hard-shell capsule is less than 170 mg. Reference claim 26 discloses that the release in acidic medium is measured in pH 1.2 medium at 37 °C for two hours, followed by measuring dissolution in pH 6.8 buffered medium, and the dosage form releases up to 30% of the 25-hydroxyvitamin D in the formulation at the 2-hour time point.
Where the reference claims appear to be deficient is with respect to the amount of calcifediol contained within the hard-shell capsule. However, the instant specification further defines the recited amounts in ¶[0118] in terms of the microgram amounts that are considered to embody the reference composition.
Additionally, the teachings of Petkovich disclose the composition of the instant invention as well and defines the amount of 25-hydroxyvitamin D compound contained therein as ranging from about 1-1,000 mcg (microgram(s)) and more narrowly from about 1-100 mcg within the capsule dosage form (see e.g., claims 21 and 22).
Thus, in view of the combined teachings, the Examiner submits that were the reference application available as prior art, it would present a person of ordinary skill in the art with a reasonable expectation of achieving the instantly claimed composition.
Reference claim 2 discloses the limitations of instant claim 2.
Reference claim 3 discloses the limitations of instant claim 3.
Reference claim 5 discloses the limitations of instant claim 5.
Reference claim 6 discloses the limitations of instant claim 6.
Reference claim 7 discloses the limitations of instant claim 7.
Reference claim 8 discloses the limitations of instant claim 8.
Reference claims 9 and 10 encompass and overlap the instantly recited range of gelatinizing agent present in the hard-shell capsule, thereby disclosing the limitations of instant claim 9.
Reference claim 11 discloses the limitations of instant claim 10.
Reference claim 12 discloses the limitations of instant claim 11.
Reference claim 18 discloses the limitations of instant claim 17.
Reference claim 20 discloses the limitations of instant claim 19.
Reference claim 21 discloses the limitations of instant claim 20.
Reference claim 23 discloses the limitations of instant claim 23.
The method disclosed by reference claim 30 is directed to providing increased recovery and/or reduced degradation of 25-hydroxyvitamin D or calcifediol in a dosage form comprising 25-hydroxyvitamin D or calcifediol after exposure of the dosage form to acidic conditions. The method is considered to disclose the recited property of instant claim 27.
The reference claims do not expressly disclose the recited property of instant claim 28. However, the composition is disclosed and in view of MPEP §2112.01(I), the Examiner submits that a person of ordinary skill in the art would reasonably expect to achieve the recited rise in total serum in the 24-hour period following the intended use of the claimed composition. Support for this can be found in Petkovich which discloses administering the instantly recited range of 25-hydroxyvitamin D compounds from a capsule formulations in order to effect controlled or substantially constant release of the 25-hydroxyvitamin D compound which is taught further as achieving substantially constant blood levels of 25-hydroxyvitamin D during the 24-hour post-dosing period. See ¶[0047] and ¶[0082].
The foregoing reference teachings in view of Petkovich (i.e., claims 21 and 22) are also considered to encompass and therefore teach the limitations recited by instant claim 30.
The recited properties of instant claims 31-37 are not expressly disclosed by the reference claims. However, the composition is disclosed in view of the teachings of Petkovich, and in further view of MPEP §2112.01(I), the Examiner submits that a person of ordinary skill in the art would reasonably expect to achieve the recited steady-state serum concentrations since the daily amounts that are recited (i.e., 30-µg and 60-µg doses) are also taught by the combination of references.
Reference claim 27 discloses the limitations of instant claim 38.
Reference claim 28 discloses the limitations of instant claim 39.
The recited properties of instant claims 40 and 41 are not expressly disclosed by the reference claims. However, the method administering the claimed composition is disclosed in view of the teachings of Petkovich, and in further view of MPEP §2112.01(I), the Examiner submits that a person of ordinary skill in the art would reasonably expect to achieve the recited baseline-adjusted steady-state Cmax.
The limitations of instant claim 45 are read on by teachings provided above with respect to reference claims 1-5, 7, and 8, further defined by the amounts disclosed by claims 21 and 22 of Petkovich.
Lastly, the limitations recited by new claims 46-48 are considered to be met by the teachings of the reference claims (e.g., claim 1) whereby the disclosed capsule contains a solid (i.e., mass or slug) or semi-solid (i.e., flowable material) composition within the hard shell.
Thus, were the reference application available as prior art, the cited claims in further view of Petkovich, would raise to the level of a prima facie case of obviousness, where they failed to anticipate the instantly claimed invention.
This is a provisional nonstatutory double patenting rejection.
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 7 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 7, the parenthetical recitation “(including kappa- carrageenan and/or iota-carrageenan)” renders the claim indefinite because it is unclear whether the limitations that follow the generic “including” term are part of the claimed invention. See MPEP §2173.05(d).
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 48 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. The limitations of amended claim 1 are discussed above. Claim 47 depends directly from claim 1 and recites that the composition is a mass or slug (i.e., solid), and that the mass or slug fills the hard capsule shell.
Claim 48 depends directly from claim 47 and recites wherein the hard-shell capsule is a coating, and whereby the coating enrobes the mass or slug of the composition.
The Examiner submits that claim 48 fails to further limit claim 47 since claim 47 already narrows the capsule contents to a solid mass or slug and fills it into the hard capsule shell. Claim 48 does not narrow this; it only rebrands the hard capsule shell as a “coating” and describes what the coating/shell does.
Applicants may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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. Applicants are 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 1-3, 5-11, 23, 27, 28, 30-39, and 46-48 are rejected under 35 U.S.C. 103 as being unpatentable over Petkovich et al. (US Pre-Grant Publication Nº 2019/0142847 A1; newly cited IDS reference) in view of Son et al. (US Pre-Grant Publication Nº 2016/0208125 A1; of record).
As amended, claim 1 recites a hard shell controlled release dosage form comprising a hard shell capsule containing a solid or semi-solid composition comprising a 25-hydroxyvitamin D compound, the hard shell is a gelatinized hard shell capsule comprising a cellulose ether and a gelatinizing agent; wherein the 25-hydroxyvitamin D compound is provided in an amount in a range of 30 µg to 1800 µg, and the dosage form releases ≤30% of the 25-hydroxyvitamin D in the formulation within the first two hours of a two-stage dissolution test at pH 1.2.
Petkovich discloses a pharmaceutical composition or oral administration comprising a 25-hydroxyvitamin D compound that is within a matrix that controllably releases the compound (see e.g., claims 1-3). Claims 19 and 20 further limit the 25-hydroxyvitamin D compound to 25-hydroxyvitamin D3 (aka calcifediol). Claim 21 discloses that the 25-hydroxyvitamin D compound is present in an amount ranging from about 1-1,000 µg (mcg), while claim 22 narrows the range to about 1-100 mcg.
Claim 9 discloses that the compound is formulated in a hard capsule shell.
The reference additionally provides compositional disclosure for the capsule, albeit in terms of materials used in the soft capsule format. Nevertheless, compounds such as gelatin, starch, carrageenan are disclosed in ¶[0104] as embodying gel-forming (i.e., gelatinizing) agents. Though Petkovich discloses formulating the instant composition in a hard capsule shell, the reference is deficient with respect to the compositional definition of the shell.
Despite disclosing the instantly claimed gelatinizing agent (e.g., carrageenan), the practiced shells of Petkovich do not expressly teach that the hard-shell capsules comprise HPMC (aka hypromellose).
Son remedies this definition disclosing hard capsules comprising a water-soluble cellulose ether and a gelation agent. The gelation agent is disclosed as representing about 0.5 parts by weight (aka percent) by weight based on 100 wt% of the water-soluble cellulose ether (see e.g., claim 1). The claim also discloses that the capsule will optionally contain up to about 0.3 wt% of a gelation aid. Claim 3 discloses that the water-soluble cellulose ether comprises HPMC. Claim 4 discloses that the gelation agent comprises carrageenan, gellan gum, xanthan gum, pectin, or a mixture thereof. Claim 5 discloses that the gelation aid comprises potassium chloride, potassium acetate, calcium chloride, or a mixture thereof.
Based on the combined teachings of the Petkovich and Son, the Examiner submits that a person of ordinary skill in the art would have had a reasonable expectation of success at producing the not only instantly claimed composition, but also the recited release property. MPEP §2112.01(I) states that “[w]here the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established” and that “[w]hen the PTO shows a sound basis for believing that the products of the Applicant and the prior art are the same, the Applicant has the burden of showing that they are not.”
In the instant case, the Examiner has provided a showing whereby the capsule formulation (e.g., hard capsule shell) possesses the newly presented release profile. However, where the reference is deficient is with respect to the compositional definition of that hard shell capsule. Son bridges this gap in teaching by disclosing hard capsule shells and their composition. As the disclosure of Son meets the compositional definition that is instantly recited for the shell, the Examiner advances that the composition of the shell would be expected to provide the release profile already disclosed by Petkovich, absent a clear showing of evidence to the contrary. Furthermore, Petkovich defines that doses termed as being “controlled release” or “sustained release” are those that are expected to release the 25-hydroxyvitamin D compound over an extended period of time, such as 4-24 hours or longer. See ¶[0048].
The foregoing disclosure is considered to teach the limitations recited by instant claims 1-3, 5-11, 30, 38, and 39. The limitations of independent claim 39 are considered to be met as the claim simply requires administration of the claimed dosage for to a subject in need of calcifediol, which Petkovich discloses (see claims 47, 49, 50, etc.).
The limitations of newly presented claims 46-48 are also taught by Petkovich. The 25-hydroxyvitamin D compound is disclosed as being formulated within a matrix that is then encapsulated, for instance, in a hard capsule shell (see e.g., claims 1, 4-6, and 9). The matrix is further taught as being formulated into a solid or semi-solid. See ¶[0101]. The solid form is considered to teach and suggest the mass/slug recitations while the semi-solid form is considered to teach the flowable form.
MPEP §2173.05(g) states that “[a] claim term is functional when it recites a feature ‘by what it does rather than by what it is’ (e.g., as evidenced by its specific structure or specific ingredients),” “[t]here is nothing inherently wrong with defining some part of an invention in functional terms,” and that “[f]unctional language does not, in and of itself, render a claim improper.” Of note with respect to the instantly claimed composition, the passage also states that “Functional language may also be employed to limit the claims without using the means-plus-function format.” However, “[u]nlike means-plus-function claim language that applies only to purely functional limitations, functional claiming often involves the recitation of some structure followed by its function.” [emphasis added]
Lastly, “[a] functional limitation is often used in association with an element, ingredient, or step of a process to define a particular capability or purpose that is served by the recited element, ingredient or step.”
In the instant case, the limitations of claims 23, 27, and 28, all depend from claim 1 and the composition and structure recited therein and add no further limitations. To this end, the Examiner considers the disclosure of Petkovich and Son to meet the compositional and structural limitations as discussed above, and thus also to meet the recited functional limitations. MPEP §2112.01(I) supports this position stating that where the structure recited in the art is substantially identical to that of the claims, claimed properties and functions are presumed to be taught as well.
The limitations of claims 31-37 are given similar consideration noting the added condition that the functional limitation is achieved when a dose amount is provided to achieve the recited function (e.g., provide a rise in serum total 25-hydroxyvitamin D in an adult male human of less than 3 ng/mL in the first 24 hours after dosing).
In the case of instant claim 31, the “amount” is broadly and reasonably considered to fall within the range of 25-hydroxyvitamin D within the capsule in claim 1 (i.e., 30-1,800 µg).
Claims 32-34 and 37 recite functional limitations that occur when a patient receives a daily dose of 60 µg. Claims 35 and 36 recite functional limitations which align with a daily dosing of 30 µg.
As discussed above, Petkovich teaches and suggests capsule which contain amounts of 25-hydroxyvitamin D compound in amounts ranging from 1-100 µg (see e.g., claim 22). Paragraphs [0082], [0083], and [0116] each disclose narrower ranges of the 25-hydroxyvitamin D compound administered which falls within the range of 1-100 µg, such as 1-50 mcg, 10-40 mcg, and 30-90 mcg. Paragraph [0113] additionally discloses that preferred formulation doses include 30 and 60 mcg of 25-hydroxyvitamin D or D3).
Thus, as claims 31-37 are directed to compositions and not methods of achieving the recited functions, the Examiner submits that Petkovich’s disclosures of the 25-hydroxyvitamin D capsule formulations containing the aforementioned doses, teach and suggest the compositional merits of the claims.
Based on the foregoing teachings of Petkovich and Son, the Examiner advances that a person of ordinary skill in the art would have had a reasonable expectation of success in producing the instantly claimed composition, and further, arriving at the recited method of delivering the composition to a patient in need thereof. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, and absent a clear showing of evidence to the contrary.
Claims 17 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Petkovich et al. (US Pre-Grant Publication Nº 2019/0142847 A1; newly cited IDS reference) and Son et al. (US Pre-Grant Publication Nº 2016/0208125 A1; of record), as applied to claim 1, further in view of Melnick et al. (US Pre-Grant Publication Nº 2019/0083513 A1; of record).
The amended limitations of claim 1 are discussed above.
The teachings of Petkovich and Son are discussed above with respect to the compositional and structural merits of the hard-shell capsule comprising 25-hydroxyvitamin D or calcifediol (25-hydroxyvitamin D3).
Of particular note is that Petkovich further defines the matrix fill of the capsule as comprising: hard paraffin (about 20 wt%), liquid paraffin or mineral oil (about 35 wt%), hydroxypropyl methylcellulose (about 10 wt%), lauroyl polyoxylglycerides (about 10 wt%), anhydrous ethanol (about 2 wt%), glycerol monostearate (a monoglyceride; about 20-25 wt%), and optionally “a small amount” of butylated hydroxytoluene (BHT) (see e.g., claim 6 and ¶[0113]).
Petkovich, which is relied upon here for its disclosure of the matrix formulation, does not teach the matrix formulation as instantly claimed. Son, which is only relied upon to further define Petkovich’s hard capsule shell formulation, also does not teach the recited matrix formulations.
Melnick discloses the composition that is contained within the recited capsule. Like Petkovich, Melnick teaches and suggests extended release calcifediol capsules (e.g., hard capsules) containing solid or semi-solid matrices that deliver calcifediol. See e.g., ¶[0064].
Paragraph [0084] discloses a particular formulation of 25-hydroxyvitamin D3 (aka calcifediol) in an extended-release, oral formulation. The dosage contains the following:
about 30-900 µg calcifediol;
about 2 wt% anhydrous/dehydrated ethanol;
about 19 wt% lauroyl polyoxyglycerides;
about 20 wt% hard paraffin;
about 23 wt% mono- and di-glycerides;
about 35 wt% liquid paraffin (i.e., mineral oil);
about 10 wt% hypromellose; and
about 0.02 wt% butylated hydroxytoluene (BHT).
Based on the combined teachings of the references, the Examiner submits that a person of ordinary skill in the art would have had a reasonable expectation of success at producing the instantly claimed composition.
As discussed above, Petkovich discloses almost all of the limitations of the compositional lists recited by claims 17 and 19, with the exception of calcifediol in terms of the weight percentage and the disclosure of the specific amounts of the mono- and di-glycerides and BHT. Melnick is already on record as providing the specific disclosure which is considered to meet the claimed limitations.
Owing to both Petkovich and Melnick as teaching the oral administration of calcifediol from a solid or semi-solid matrix within a hard capsule, the Examiner submits that the ordinarily skilled artisan would reasonably expect to achieve the instantly claimed composition by modifying the matrix composition of Petkovich with the matrix disclosed by Melnick.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, and absent a clear showing of evidence to the contrary.
Claims 20, 29, and 45 are rejected under 35 U.S.C. 103 as being unpatentable over Petkovich et al. (US Pre-Grant Publication Nº 2019/0142847 A1; newly cited IDS reference) and Son et al. (US Pre-Grant Publication Nº 2016/0208125 A1; of record), as applied to claims 1-3 and 5-11, further in view of Yamamoto et al. (USPN 5,756,123 A; of record) and as evidenced by Nagahara et al. (EP 1 607 088 B1; of record).
As amended, claim 1 recites a hard shell controlled release dosage form comprising a hard shell capsule containing a solid or semi-solid composition comprising a 25-hydroxyvitamin D compound, the hard shell is a gelatinized hard shell capsule comprising a cellulose ether and a gelatinizing agent; wherein the 25-hydroxyvitamin D compound is provided in an amount in a range of 30 µg to 1800 µg, and the dosage form releases ≤30% of the 25-hydroxyvitamin D in the formulation within the first two hours of a two-stage dissolution test at pH 1.2.
Claim 29 newly recites that the hard-shell capsule of claim 1 is sealed with a hypromellose (HPMC) sealing solution.
Petkovich discloses a pharmaceutical composition or oral administration comprising a 25-hydroxyvitamin D compound that is within a matrix that controllably releases the compound (see e.g., claims 1-3). Claims 19 and 20 further limit the 25-hydroxyvitamin D compound to 25-hydroxyvitamin D3 (aka calcifediol). Claim 21 discloses that the 25-hydroxyvitamin D compound is present in an amount ranging from about 1-1,000 µg (mcg), while claim 22 narrows the range to about 1-100 mcg.
Claim 9 discloses that the compound is formulated in a hard capsule shell.
The reference additionally provides compositional disclosure for the capsule, albeit in terms of materials used in the soft capsule format. Nevertheless, compounds such as gelatin, starch, carrageenan are disclosed in ¶[0104] as embodying gel-forming (i.e., gelatinizing) agents. Though Petkovich discloses formulating the instant composition in a hard capsule shell, the reference is deficient with respect to the compositional definition of the shell.
Despite disclosing the instantly claimed gelatinizing agent (e.g., carrageenan), the practiced shells of Petkovich do not expressly teach that the hard-shell capsules comprise HPMC (aka hypromellose).
Son remedies this definition disclosing hard capsules comprising a water-soluble cellulose ether and a gelation agent. The gelation agent is disclosed as representing about 0.5 parts by weight (aka percent) by weight based on 100 wt% of the water-soluble cellulose ether (see e.g., claim 1). The claim also discloses that the capsule will optionally contain up to about 0.3 wt% of a gelation aid. Claim 3 discloses that the water-soluble cellulose ether comprises HPMC. Claim 4 discloses that the gelation agent comprises carrageenan, gellan gum, xanthan gum, pectin, or a mixture thereof. Claim 5 discloses that the gelation aid comprises potassium chloride, potassium acetate, calcium chloride, or a mixture thereof.
Neither the teachings of Petkovich nor Son expressly disclose their respective hard capsule shells in terms of the compositional limitations of claims 20, 29, and 45.
Yamamoto cures these deficiencies.
Yamamoto discloses a water-soluble cellulose derivative-based hard-shell capsules that encapsulates and delivers active pharmaceutical drugs (see e.g., Abstract). Like, Son, Yamamoto discloses shells comprising HPMC, a gelatinizing agent, and a gelling promoter. Example 1, Table 1 (shown below):
PNG
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479
539
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The practiced capsule shell expressly meets the capsule limitations of claims 1-3 and 5-11. Regarding the limitations of claim 45, the above Example further discloses that the HPMC that is used in preparing the capsule shell, possesses the same viscosity as a 1/1 mixture of TC-5MW and TC-5EW blends of HPMC. When measured as 2% aqueous solutions at 20ºC, the two blends have viscosities measuring 4.5 and 3.0 centistokes (see col. 7, lines 19-25). The former TC-5MW HPMC blend’s viscosity when measured at the same conditions is about 4 mPa·s (cPs). The state of the art supports this (see Nagahara; pg. 7, lines 55-57). The disclosure of HPMC thus meets the limitations of claim 45.
Regarding the limitations of claim 20, the Examiner acknowledges that the relied upon example does not disclose using gellan gum, but instead uses carrageenan. The remaining limitations of the claim are met regarding the amount of titanium dioxide and HPMC.
Son discloses the gelation agent of its practiced hard-shell capsules may include carrageenan, gellan gum, xanthan gum, pectin, or mixtures thereof, thereby teaching and suggesting that they are functionally equivalent gelling agents for forming hard capsule shells. See ¶[0116] of Son. MPEP §2144.06(II) states that “[i]n order to rely on equivalence as a rationale supporting an obviousness rejection, the equivalency must be recognized in the prior art, and cannot be based on Applicant’s disclosure or the mere fact that the components at issue are functional or mechanical equivalents.” In the instant case, Son provides the requisite disclosure demonstrating that the two agents are functionally interchangeable for preparing hard capsule shells.
Lastly, regarding claim 29, the Examiner notes that Table I additionally discloses an HPMC immersion solution which is further disclosed as being applied to hard capsule shells by means of a simple dipping technique (see e.g., col. 3, lines 38-45).
Based on the combined teachings of the references, the Examiner submits that a person of ordinary skill in the art would have had a reasonable expectation of success at producing the instantly claimed hard-shell compositional limitations.
The Examiner acknowledges that Petkovich teaches and suggests gelling agent compositions that form the basis of the hard shell, but relies on the teachings of Son to meet the more specific limitations such as the combination of the gelling agent (e.g., gellan gum, carrageenan, or mixtures thereof) with gelling aids/promoters and cellulose ethers (e.g., HPMC).
The more specific limitations (e.g., claims 20 and 45) are not expressly met by Son, but are taught and suggested by Yamamoto. Yamamoto additionally discloses the newly presented limitations of adding an HPMC coating solution to the hard-shell capsules via dipping technique. Yamamoto discloses that doing so improves the shapability and disintegration ability of the HPMC hard shell capsules.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, and absent a clear showing of evidence to the contrary.
Claims 40 and 41 are rejected under 35 U.S.C. 103 as being unpatentable over Petkovich et al. (US Pre-Grant Publication Nº 2019/0142847 A1; newly cited IDS reference) and Son et al. (US Pre-Grant Publication Nº 2016/0208125 A1; of record), as applied to claims 1 and 39, further in view of DeLuca et al. (USPN 8,759,328 B2) and further evidenced by Boone (The K-Zone: Biophysical data tables: standard man; 2006).
The limitations of claims 1 and 39 are discussed above.
The teachings of Petkovich and Son are also discussed above as teaching the instantly claimed composition of claim 1, specifically noting that a hard-shell capsule oral formulation comprising calcifediol (25-hydroxyvitamin D3) in an amount ranging from 30-1,800 µg of the composition is in a solid or semi-solid matrix, encapsulated further in a shell comprising a cellulose ether (HPMC) and a gelling agent. Claim 39 is additionally considered to be met, particularly as it simply requires the administration of the composition to a patient in need of such a dosage form.
Neither reference, however, expressly discloses that the method results in the recited baseline-adjusted steady state Cmax of serum calcifediol ranging from about 25-98 ng/mL (claim 40) or from about 12.5-104.9 ng/mL (claim 41).
DeLuca is considered to provide disclosure supportive of this result.
DeLuca discloses oral dosage forms in the form capsules that comprise a solid oral dosage form consisting of a shell and a filling, whereby the shell is composed of a single sealed enclosure which may be made from gelatin, starch, or cellulose, or other suitable materials, and may be hard (see e.g., col. 8, lines 4-10). The practiced oral dosage forms disclose administering repeated, single-day doses of 25-hydroxyvitamin D3 in order to elevate the serum level in a human to a concentration of 25-hydroxyvitamin D3 to be in the range of 30-200 ng/mL (see e.g., Abstract; claims). The oral dosage form is further defined as having a single dose that is in the range of 10-100 µg/kg body weight, and more narrowly, a range of 30-50 µg/kg body weight of 25-hydroxyvitamin D3 (see e.g., claims 7 and 8). As further evidenced by Boone, the “standard man” is considered to have a mass of 70 kg. A daily dose of about 10-25.5 µg/kg body weight results in a 25-hydroxyvitamin D3 dose ranging from about 700-1,800 µg per day, thereby meeting the claimed composition, the recited method of claim 39, and lastly the limitations of claims 40 and 41 which require a dose that results in the establishment of the serum levels of 25-hydroxyvitamin D3.
Based on the combined teachings of the references, the Examiner submits that a person of ordinary skill in the art would have had a reasonable expectation of success at producing the instantly claimed composition and arriving at the results achieved by the recited method of treatment. As further evidenced by the teachings of DeLuca and Boone, the Examiner submits that the ordinarily skilled artisan would have expected an administered dose according to the instant invention to produce the recited serum levels of 25-hydroxyvitamin D3.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, and absent a clear showing of evidence to the contrary.
All claims have been rejected; no claims are allowed.
Conclusion
Applicants’ submission of an information disclosure statement under 37 CFR 1.97(c) with the fee set forth in 37 CFR 1.17(p) on 9 June 2025 prompted the new grounds of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP §609.04(b). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Correspondence
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Jeffrey T. Palenik whose telephone number is (571) 270-1966. The Examiner can normally be reached on 9:30 am - 7:00 pm; M-F (EST).
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Robert A. Wax can be reached on (571) 272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Jeffrey T. Palenik/
Primary Examiner, Art Unit 1615
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