DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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.
This office action is a response to applicant’s communication submitted August 4, 2023. This application is a continuation of 17/675,170 filed February 18, 2022 and claims the benefit of provisional US application 63/150,908 filed February 18, 2021.
Claims 1-45 and 47-50 are pending in this application.
Information Disclosure Statement
The information disclosure statement (IDS) dated 9/13/2023 comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, the IDS documents have been placed in the application file and the information therein has been considered as to the merits.
Specification
The disclosure is objected to because of the following informalities: the phrase “derivates” appears throughout the specification, which should read “derivatives” (pg. 1, para. 0004, pg. 2, top of page and middle of page (three times total), pg. 3, middle of page (twice), pg. 9, para. 0028, pg. 15, top of page).
Appropriate correction is required.
The use of trade names or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 4-6, 10-23, 27-34, and 38-45 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claim. See MPEP § 608.01(n). Accordingly, the claims 4-6, 10-23, 26-34, and 38-46 not been further treated on the merits.
Claims 1, 3, 25-26 are objected to because of the following informalities:
In claims 1, 3, and 26 The phrase “derivates” should read “derivatives”. The Examiner notes to see 112(b) rejections below regarding the phrase.
Claim 25 recites the phrase “increased risk on progressive” which should read “increased risk of progressive”.
Claims 48 objected to under 37 CFR 1.75 as being a substantial duplicate of claim 47. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Appropriate correction is required.
Claim Interpretation
Regarding claims 47 and 48 which are drawn a pharmaceutical composition and recite the phrases “effective to alleviate or reduce” and “effective to treat” respectively. The Examiner notes that it is well settled that “intended use” of a composition or product, e.g., “effective to treat”, will not further limit claims drawn to a composition, so long as the prior art discloses the same composition comprising the same ingredients in an effective amount, as the instantly claimed (See MPEP 2111.02 (II)).
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 1-3, 7-9, 24-26, 35-37, and 47-50 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.
Regarding claims 1-3, 7-9, 24-26, 35-37, and 47-50: The recitation “a derivative thereof", “derivative thereof”, or “derivatives” in claims 1-3, 7-9, 24, 26, 35-36, 47-48 renders the claims and their dependent claims herein indefinite. Applicants recite “derivative” in multiple paragraphs in the specification (pages 1-2, para. 0004, pg. 2, para. 0005). On page 6, applicants describe “derivative thereof (e.g., 2-hydroxypropyl-beta-cyclodextrin)” (para. 0014). On pages 14-15 applicant’s describe “cholesterol (and/or cholesterol derivatives)” (para. 0042). However, exemplification is not an explicit definition. Thus, there is no clear definition of “derivative" provided in the specification, and therefore it does not set forth the metes and bounds of the term “derivative”.
According to the Merriam-Webster’s Online Dictionary, “derivative” is defined as “a chemical substance related structurally to another substance and theoretically derivable from it.” (Merriam-Webster, 2023, cited on PTO-892). Hence, one of ordinary skill in the art could not ascertain and interpret the metes and bounds of the patent protection desired as to “a derivative thereof” herein. One of ordinary skill in the art would clearly recognize that a "derivative" would read on those compounds having any widely varying groups that could be used to substitute the compound. Any significant structural variation to a compound would be reasonably expected to alter its properties; e.g. physical, chemical, physiological effects and functions. Thus, it is unclear and indefinite as to how the “derivative” herein is encompassed thereby.
Regarding claims 1-3, 8, 25-26, and 47: A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance:
Claim 1 recites the broad recitation “amount”, and the claim also recites “e.g., concentration” which is the narrower statement of the range/limitation. Additionally the phrase "e.g." renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). The Examiner notes that each use of parenthesis within the claim renders the claim indefinite for the same reason as described above.
Claim 2 recites the broad recitation “size”, and the claim also recites “e.g., average size, maximum size” which is the narrower statement of the range/limitation. Additionally the phrase "e.g." renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). The Examiner notes that each use of parenthesis within the claim renders the claim indefinite for the same reason as described above.
Claim 3 recites the broad recitation “amount”, and the claim also recites “e.g., concentration” which is the narrower statement of the range/limitation. Additionally the phrase "e.g." renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). The Examiner notes that each use of parenthesis within the claim renders the claim indefinite for the same reason as described above.
Claim 8 recites the broad recitation “size”, and the claim also recites “e.g., average size, maximum size” which is the narrower statement of the range/limitation. The Examiner notes that each use of parenthesis within the claim renders the claim indefinite for the same reason as described above.
Claim 25 recites the broad recitation “progressive atherosclerotic heart disease”, and the claim also recites “accelerated or early onset” which is the narrower statement of the range/limitation. Additionally the phrase "including" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 26 recites the broad recitation “circulating cholesterol crystals”, and the claim also recites “e.g., blood, serum, plasma” and “and/or clots comprising cholesterol crystals which are the narrower statements of the range/limitation. Additionally the phrase "e.g." renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). The Examiner notes that each use of parenthesis within the claim renders the claim indefinite for the same reason as described above.
Claim 47 recites the broad recitation “circulating cholesterol crystals”, and the claim also recites “e.g., blood, serum, plasma” and “and/or clots comprising cholesterol crystals which are the narrower statements of the range/limitation. Additionally the phrase "e.g." renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). The Examiner notes that each use of parenthesis within the claim renders the claim indefinite for the same reason as described above.
The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Regarding claim 49: Claim 49 recites inter alia, “formulated for single dose or repeated administration.”. It is unclear whether the claim is merely reciting an intended use or method limitation, wherein the composition is intended to be administered in multiple single doses. It is unclear how a single pharmaceutical composition can be administered repeatedly. In short, the claim can be interpreted as if the pharmaceutical composition is administered, recycled and administered again or wherein the dosage is modified in such a way to facilitate long term treatment. It is unclear what structure is encompassed by limiting a composition to be administered repeatedly. The instant specification merely states with respect to this limitation, “….the pharmaceutical composition is formulated for single dose or repeated administration (pg. 7, para. 0016). The multiple interpretations that arise from the claim render the claim indefinite.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3, 7-9, 24-26, 35-37, 47-49 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhang (CN 107854448, cited on PTO-892) as evidenced by PubChem (2-hydroxypropyl-beta-cyclodextrin, 2026, cited on PTO-892) and Zimmer (Sci. Trans. Med., 2016, cited on PTO-892). The English Translation of Zhang relied upon has been provided by the Examiner.
Regarding claims 1-3, 7-9, 24-26, 35-37, 47-49: Zhang teaches a nicotinic acid tablet comprising nicotinic acid, coatings made of Lovastatin, and hydroxypropyl beta cyclodextrin (English translation, abstract, pg. 2, para. 6). According to PubChem 2-hydroxypropyl-beta-cyclodextrin and hydroxypropyl beta cyclodextrin are synonymous (pgs. 5-6, section 2.4 Synonyms). Zhang teaches that Lovastatin has been listed in China’s national essential drugs that is mainly used to treat heterozygous familial hypercholesterolemia, serious primary property hypercholesterolemia, light-duty primary hypercholesterolemia (English translation, pg. 2, para. 6). Zhang teaches lovastatin reduces low-density lipoprotein (i.e. LDL) in blood (English translation, pg. 2, para. 6). Zhang teaches the preparation offers clinical benefit over the individual groups of medicines alone (English translation, pg. 2, paras. 6-7). According to the instant specification, the effective amount is from about 4g to about 250 g (pg. 5, para. 0009). Zhang teaches formulations comprising 6 g hydroxypropyl-beta-cyclodextrin (English translation, embodiment 2, middle of page). Although Zhang does not explicitly teach a method of administering for the treatment of heterozygous familial hypercholesterolemia, given that Zhang explicitly describes such a disease is typically treated with medications containing Lovastatin, a person of ordinary skill in the art upon reading the reference would at once envisage the claimed application of treating familial hypercholesterolemia with the composition of Zhang (See MPEP 2131.02 (III)). Additionally Zimmer discloses that 2-hydroxypropyl-beta-cyclodextrin is effective at increasing cholesterol crystal dissolution and demonstrates a reduction in crystal size (abstract, pg. 25, figure 3F). Wherein the specific disease is treated with an effective amount of hydroxypropyl beta cyclodextrin, the resulting properties (i.e. reducing size of cholesterol crystals, promoting clearance of cholesterol, reducing a complication, reducing treatment recited by instant claims 2-3, 8, and 24-26, and 35-36 are inherent properties of practicing the method and treating the underlying condition. There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference (See MPEP 2112 (II)).
Claims 47-50 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Fornoni (WO 2013/155485, cited on PTO-892) as evidenced by PubChem (2-hydroxypropyl-beta-cyclodextrin, 2026, cited on PTO-892).
Regarding claims 47-50: Fornoni teaches compositions comprising hydroxypropyl B cyclodextrin an a pharmaceutically acceptable vehicle for injectable administration (pgs. 5-6, para. 0021, pg. 30, para. 00107). According to PubChem 2-hydroxypropyl-beta-cyclodextrin and hydroxypropyl beta cyclodextrin are synonymous (pgs. 5-6, section 2.4 Synonyms). Fornoni also notes that,
“2-Hydroxypropyl-/3-cyclodextrin (2-HP~CD), a strong cholesterol
acceptor, is an effective way to sequester cholesterol and to protect any cell
affected by diabetes, prediabetes, metabolic syndrome and obesity from
cholesterol dependent damage in vivo and in vitro.”
(pg. 30, para. 00107). Fornoni teaches doses comprise about 2-20 mg/kg/day to about 4000 mg/kg three to five times per week, totaling up to about 20,000 mg/kg/week (pg. 6, para. 0025). Wherein Fornoni teaches injections weekly (pg. 9, para. 0037), the limitation with respect to formulation for single dose or repeated dose is met. According to the instant specification, the effective amount is 50 mg/kg to about 8,000 mg/kg. Thus, the compositions of Fornoni are in an effective amount comparable to the instantly claimed composition and are thus anticipated.
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.
Claims 1-3, 7-9, 24-26, and 35-37 are rejected under 35 U.S.C. 103 as being unpatentable over Fornoni (WO 2013/155485, cited on PTO-892) and PubChem (2-hydroxypropyl-beta-cyclodextrin, 2026, cited on PTO-892) as applied to claims 47-50 above in view of Zhang (CN 107854448, cited on PTO-892) and Zimmer (Sci. Trans. Med., 2016, cited on PTO-892).
Regarding claims 1-3, 7-9, 24-26, and 35-37: As discussed above, Fornoni teaches a composition of claims 47-50 comprising an effective amount of 2-Hydroxypropyl-/3-cyclodextrin (2-HP~CD) as an effective way to sequester cholesterol and to protect any cell affected by diabetes, prediabetes, metabolic syndrome and obesity from cholesterol dependent damage in vivo and in vitro. Fornoni further teaches the method includes cyclodextrin or derivatives thereof (pg. 1, para. 001). Fornoni suggests that therapeutic control of systemic hypercholesterolemia is critically important in the clinical management and treatment of obesity, metabolic syndrome, pre-diabetes and diabetes (pg. 1, para. 001). Fornoni teaches that current treatments to lower cholesterol levels in patients rely on using statins to lower plasma LDL, but do not lower plasma membrane or cellular cholesterol (pg. 10, para. 0041). Fornoni teaches the method is effective at reducing cholesterol levels in calls of the body (pg. 15, paras. 0062-0063). Fornoni teaches the cyclodextrin can be in combination with lovastatin (pg. 16, para. 0068). Fornoni teaches treatment with cyclodextrin resulted in a significant reduction of cholesterol in the kidney cortex (i.e. renal cholesterol clearance, pg. 25, para. 0098).
Fornoni does not teach wherein the method is applied to the treatment of familial hypercholesterolemia as instantly claimed.
However, Zhang teaches that Lovastatin has been listed in China’s national essential drugs that is mainly used to treat heterozygous familial hypercholesterolemia, serious primary property hypercholesterolemia, light-duty primary hypercholesterolemia (English translation, pg. 2, para. 6). Zhang teaches lovastatin reduces low-density lipoprotein (i.e. LDL) in blood (English translation, pg. 2, para. 6). Additionally Zimmer discloses that 2-hydroxypropyl-beta-cyclodextrin is effective at increasing cholesterol crystal dissolution and demonstrates a reduction in crystal size (abstract, pg. 25, figure 3F).
Taken together, it would have been prima facie obvious to a person of ordinary skill in the art to modify the method of Fornoni by applying it to the treatment of heterozygous familial hypercholesterolemia as taught by Zhang. A person of ordinary skill in the art would have had the motivation to do so as 2-Hydroxypropyl-/3-cyclodextrin is a known therapeutic for sequestering cholesterol which is a known pathway for control of systemic hypercholesterolemia and patients with familial hypercholesterolemia are known in the art and are in need of treatment. Wherein the specific disease is treated with an effective amount of hydroxypropyl beta cyclodextrin, the resulting properties (i.e. reducing size of cholesterol crystals, promoting clearance of cholesterol, reducing a complication, reducing treatment) recited by instant claims 2-3, 8, and 24-26, and 35-36 naturally flow as a result off practicing the method and treating the underlying condition. Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention (See MPEP 2145 (II)).
Conclusion
No claims are allowed in this action.
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/S.L.G./Examiner, Art Unit 1693
/ANDREA OLSON/Primary Examiner, Art Unit 1693