DETAILED ACTION
Claims 15-29 are pending in the instant application.
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 .
Priority
The instant application claims priority to 371 of PCT/EP2022/057006 filed 03/17/2022 which claims priority to EPO 21163104.9 filed 03/17/2021.
Information Disclosure Statement
The information disclosure statement (IDS) is in compliance with the provisions of 37 CFR 1.97, except where noted. Accordingly, the information disclosure statement was considered by the examiner. Please see attached initialed Forms 1449.
Claim Objections
Claim 18 is objected to because of the following informalities: ‘have diameter’ should be corrected to ‘have a diameter’.
Claim 19 is objected to because of the following informalities: ‘wherein it’ should be corrected to ‘wherein the formulation’.
Claim 25 is objected to because of the following informalities: ‘the second’ in step (d) should be corrected to ‘the second mixture’.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 15-17 and 26 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 15 includes transitional phrases ‘comprising’, ‘consisting essentially of’, and/or ‘consisting of’. The transitional phrases define the scope of a claim with respect to what unrecited additional components or steps, if any, are excluded from the scope of the claim. The presence of more than one transitional phrase makes it impossible to determine the scope of the claim. For examination purposes the transitional phrase, “comprising” is being used.
Regarding claim 15, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 16 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. Claim 16 blur the metes and bounds of the claims due to wording “and/or”.
Claim 17 recites the limitation "adjusted". There is insufficient antecedent basis for this limitation in the claim. The specification does not define what “adjusted” means.
Claim 25 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. Claim 25 blur the metes and bounds of the claims due to wording “in particular”. The examiner cannot determine if the words proceeding are exemplary or limited to these terms. Regarding claim 25, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 112(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.
Claims 21-24 are 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 formulation “for use as a medicament in the treatment of a Vitamin D deficiency” does not further limit the makeup of formulation. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 15 and 18-19 are rejected under 35 U.S.C. 102(a)(1)(a)(2) as being anticipated by Male et al. (WO 2019/175830 A1) hereinafter referred to as Male.
Male discloses stable oral nanoemulsion formulations comprising cholecalciferol and tocophersolon (Vit E TPGS or Vitamin E with polyethylene glycol) (Abstract). The invention was aimed to develop a nanoemulsion comprising an aqueous dispersion and dispersed phase. The nanoemulsion containing a pharmaceutically active ingredient. The stabilization of nanoemulsion is achieved by using D-a-tocopherol polyethylene glycol succinate (TPGS) (pg 6, lines 10-15). Because of TPGS’ amphiphilic nature, it forms micelles and stabilizes the nanoemulsion at a concentration as low as 0.02% (pg 3, lines 1-5). Male discloses a stable cholecalciferol nanoemulsion comprising tocopherol polyethylene glycol succinate (TPGS) (claims 1-3); such a nanoemulsion would have micelles entrapping cholecalciferol. The particle size ranges from 15 to 1000 nm (pg 6, lines 19-20). The chelating agents used in the invention are selected from the group including citric acid (pages 7-8). Example 1 includes 60,000 IU of cholecalciferol (Vitamin D3) (40,000 IU/mg X 1.5 mg = 60,000 IU) (pg 10).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 15-24 and 26-29 are rejected under 35 U.S.C. 103 as being unpatentable over Male et al. (WO 2019/175830 A1), Buck et al. (US 2011/0052707 A1), and Neutze et al. (Pharmacologic Therapy for Vitamin D Deficiency, FPIN’s Clinical Inquiries, 2013).
Male discloses stable oral nanoemulsion formulations comprising cholecalciferol and tocophersolon (Vit E TPGS or Vitamin E with polyethylene glycol) (Abstract). The invention was aimed to develop a nanodispersion comprising an aqueous dispersion and dispersed phase. The nanodispersion containing a pharmaceutically active ingredient. The stabilization of nanodispersion is achieved by using D-a-tocopherol polyethylene glycol succinate (TPGS) (pg 6, lines 10-15). Because of TPGS’ amphiphilic nature, it forms micelles and stabilizes the nanodispersion at a concentration as low as 0.02% (pg 3, lines 1-5). The particle size ranges from 15 to 1000 nm (pg 6, lines 19-20). The chelating agents used in the invention are selected from the group including citric acid (pages 7-8). Example 1 includes 60,000 IU of cholecalciferol (Vitamin D3) (40,000 IU/mg X 1.5 mg = 60,000 IU) (pg 10).
Nanoemulsion-based delivery systems have been found to be suitable for improving the oral administration of oil-soluble vitamins. Nanoemulsions are transparent or slightly turbid liquids (pg 2, lines 1-3).
Male does not explicitly mention 25(OH)D levels.
Buck discloses compositions comprising Vitamin D (cholecalciferol and/or ergocalciferol) and 25(OH)D3 (calcifediol), and use of those compositions to affect at least concentration, bioavailability, metabolism, or efficacy of Vitamin D in a human (Abstract). Buck teaches that the increase of plasma 25(OH)D increases synergistically when a person is administered a combination of Vitamin D and 25(OH)D3 ([0014]). The peak concentration of 25(OH)D achieved by such administration may be from 30 nmol/L to 375 nmol/L ([0037]).
Male discloses compositions comprising Vitamin D and TPGS. Buck discloses that Vitamin D increases 25(OH)D levels. Therefore, it would have been obvious to one of ordinary person in the art before the effective filing date of the claimed invention to have combined teachings of above to create a formulation comprising Vitamin D and TPGS that increases 25(OH)D level in blood. This is taking some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Neutze discloses dosing regimen for Vitamin D deficiency. There is no consensus on an adequate vitamin D level, but most experts recommend a level of greater than 30 ng/mL (74.88 nmol/L) (pg 1). A review of two RCTs on vitamin D repletion concluded that daily oral dosages of 1,160 to 2,200 IU (depending on the degree of deficiency) are needed to reach and maintain serum levels greater than 30 ng/mL. An RCT of 48 women 73-89 years of age compared daily (1,500 IU), weekly (10,500 IU), and monthly (45,000 IU) cholecalciferol repletion therapy with the same cumulative dose of 90,000 IU over two months. At two months, there was no significant difference among groups in the final vitamin D level (pg 2). The Endocrine Society recommends that adults who are deficient in vitamin D receive 50,000 IU of ergocalciferol or cholecalciferol weekly for eight weeks (pg 2). Furthermore, one of ordinary skill in the art would modify dosing regimen for treating vitamin D deficiency based on the patient characteristic, organ functions, deficiency severity and many other factors. One of ordinary skill in the art would routinely experiment with different dosing regimen to alleviate vitamin D deficiency.
Therefore, it would have been obvious to one of ordinary person in the art before the effective filing date of the claimed invention to have combined teachings of above to create a formulation comprising Vitamin D, tocopherol polyalkylene glycol that will increase blood serum concentration of 25(OH)D. This is taking some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Regarding claim 16, liquid form is discussed above.
Regarding claim 17, blood concentration of 25(OH)D is discussed above.
Regarding claim 18, particle size is discussed above.
Regarding claim 19, Vitamin D dose is discussed above
Regarding claim 20, Male discloses an example comprising 150 mg of TPGS and 1.5 mg Vitamin D. The ranges overlap with what is claimed.
Regarding claim 21, Buck discloses the use of 25(OH)D3 and Vitamin D to alleviate symptoms of Vitamin D deficiency ([0040]).
Regarding claims 22-24 and 28, dosing regimen is discussed above. One of ordinary skill in the art would routinely experiment with different dosing regimen to determine therapeutic efficacy as well as individual patient safety.
Regarding claims 26-27, Buck discloses that a kit is provided which comprises of multiple, separate dosages of Vitamin D or Vitamin D3 along with a dosage of 25(OH)D3. They may be enclosed in a container. Further, instructions for administering the composition as a dosage to a human are provided within the kit ([0033]). A kit may be comprised of one, two, three, four, five, six, seven, eight, nine, ten, eleven, or twelve weekly or monthly dosages ([0061]). One of ordinary skill in the art would create a kit comprising many different loading/maintenance doses that is convenient for patients.
Regarding claim 28, weight percent of vitamin D is discussed above.
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Male et al. (WO 2019/175830 A1), Buck et al. (US 2011/0052707 A1), and Neutze et al. (Pharmacologic Therapy for Vitamin D Deficiency, FPIN’s Clinical Inquiries, 2013) as applied to claims 15-24 and 26-29 above, and further in view of Patil et al. (Nanostructured lipid carriers as a potential vehicle for Carvedilol delivery: Application of factorial design approach. Artificial Cells, Nanomedicine, and Biotechnology, 2016).
Patil discloses nanostructured lipid carriers (NLC) to augment oral bioavailability of an active drug such as carvedilol (CAR) (Abstract). Preparation of CAR-loaded NLC is disclosed – CAR-NLCs were formulated using high pressure homogenization method. Initially, glyceryl monostearate (GMS) was melted followed by oleic acid and CAR. Poloxamer 188 and Tween 80 were dissolved in 80 mL hot distilled water (aqueous phase). The lipid phase was mixed with aqueous phase. After stirring, it resulted into formation of a pre-emulsion (Preparation of CAR-loaded NLC section).
Patil discloses a process for producing an emulsion comprising a lipid and an active ingredient similar to claim 25. Therefore, it would have been obvious to one of ordinary person in the art before the effective filing date of the claimed invention to have produced a formulation comprising a lipid vehicle encapsulating an active ingredient such as carvedilol and/or vitamin D. This is taking some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN SEUNGJAI KWON whose telephone number is (571)272-7737. The examiner can normally be reached Mon - Fri 8:00 - 5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert A. Wax can be reached at 571-272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JOHN SEUNGJAI KWON/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615