DETAILED ACTION
Claims 1-14 and 16-21 are pending.
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 filed 11/3/2023 is a National Stage entry of PCT/US2022/027697, with an International Filing Date of 5/4/2022. PCT/US2022/027697 claims Priority from Provisional Application 63184001, filed 5/4/2021. PCT/US2022/027697 claims Priority from Provisional Application 63184029 , filed 5/4/2021.
Information Disclosure Statement
The Information Disclosure Statement (IDS) submitted on 11/3/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the Information Disclosure Statement being considered by the Examiner.
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.
Claims 12-14 and 16-21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Whigham et al. “Safety profile of conjugated linoleic acid in a 12-month trial in obese humans,” Food and Chemical Toxicology 42 (2004) 1701–1709.
Claim 12 is directed to a dietary supplement, feed, or foodstuff or beverage formulation effective for treating a Snord116 deficiency disease or a symptom thereof in a subject in need thereof or treating hypogonadism in a subject having a Nhlh2 deficiency, disease, or symptom thereof in a subject in need thereof, the dietary supplement comprising: an amount of conjugated linoleic acid (CLA) or a formulation thereof such that the dietary supplement delivers an effective amount of the CLA to the subject in need thereof in one or more doses, optionally 1-3 doses.
Instant claim 12 is directed towards an intended use, “for treating a Snord116 deficiency disease or a symptom thereof in a subject in need thereof or treating hypogonadism in a subject having a Nhlh2 deficiency, disease, or symptom thereof in a subject.” The intended use doesn’t have a structural requirement, and simply informs the public as to what the dietary supplement, feed, or foodstuff or beverage formulation is used for. Therefore if the supplement in the art has an amount of conjugated linoleic acid (CLA) or a formulation thereof such that the dietary supplement would deliver an effective amount of the CLA to the subject in need thereof in one or more doses, the art is anticipatory. Instant claim 13 is also the intended use.
Whigham teaches using Clarinol. Clarinol is
PNG
media_image1.png
238
446
media_image1.png
Greyscale
Whigham teaches giving 7.5 g/day Clarinol, which is 6 g/day of CLA mixed isomers. In six 1.25 g capsules per day containing either Clarinol. This is at least 1g/day, meeting instant claim 14. This is a supplement comprising a mixture of CLA isoforms, meeting instant claim 16 and 17. Instant claim 18 recites the result of a method step, after the intended use. Since instant claim 18 id directed to a composition of matter, this does not lend to the patentability of the claim and is anticipated by the structure of the supplement taught by Whigham. Instant 19 is met, as the oil in the capsule is a liquid. Claim 20 requires “adapted for daily use,” this is met as the capsules were used daily. 21 requires use in a mammal, this is the intended use and does not lend to patentability, though Whigham teaches giving the supplement to a human.
Claims 12-14 and 16-21 are anticipated.
Claim Rejections - 35 USC § 103
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 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 1-14 and 16-21 are rejected under 35 U.S.C. 103 as being unpatentable over Mortitz, WO 2018/085440 Al published 5/11/2018; in further view of Whigham et al. “Safety profile of conjugated linoleic acid in a 12-month trial in obese humans,” Food and Chemical Toxicology 42 (2004) 1701–1709; Muscatelli US 20130102528 A1 published 4/25/2013; and Kumar et al “Male hypogonadism: Symptoms and treatment,” J. Adv. Pharm. Tech. Res. 1:3 2010.
Claim 1 is directed towards a method of treating a Snord116 deficiency, disease, or a symptom thereof in a subject in need thereof or treating hypogonadism in a subject having a Nhlh2 deficiency, disease, or symptom thereof, the method comprising: administering an effective amount of conjugated linoleic acid (CLA) or a formulation thereof to the subject in need thereof, optionally wherein the effective amount is administered in one or more doses.
Moritz teaches the reduction and/or prevention of muscle loss by administration of conjugated linoleic acid (CLA) and vitamin D. Moritz states one cause for muscle is the decrease of testosterone [0041]. Moritz teaches giving Clarinol CLA (claim 76) and from about 2.0 g to about 4.0 g per day (claim 86). Moritz doesn’t teach what Clarinol CLA is, or treating a symptom of Snord116 deficiency.
Whigham teaches what Clarinol CLA is:
PNG
media_image1.png
238
446
media_image1.png
Greyscale
Whigham shows that Clarinol CLA is anticipatory to the required composition of matter required by the claims, see the 102 Rejection above. Whigham doesn’t teach treating a symptom of Snord116 deficiency.
Muscatelli teaches:
[0002] Prader-Willi syndrome is a rare genetic disease (PWS; OMIM 176270). PW patients present a complex and progressive phenotype with mainly two phases. From birth until 2-3 years old, patients present feeding impairment with poor suckling and failure to thrive, a severe hypotonia, which tends later to disappear. Paradoxally, from this period they develop hyperphagic obesity. Patients also present many other symptoms such as respiratory distress, growth retardation due to growth hormone deficiency, hypogonadism, sleep disturbances, cognitive difficulties, skin picking, high pain threshold (Bittel and Butler 2005; Muscatelli 2008; Cassidy and Driscoll 2009) behavioural problems and psychiatric troubles probably related with social dysfunctions.
[0003]To date, no comprehensive pathophysiological mechanisms have clearly been identified, however much of the phenotype of PWS, including feeding problems, may be consistent with a hypothalamic defect (Swaab 1997). Human studies have mainly focused on hormone and neuropeptide dysregulation that might contribute to the phenotype in adult PW patients, but these dosages have been performed on plasma issued from patients and controls. In parallel, few studies have been reported on histological analysis from Prader-Willi patients' hypothalamus.
[0004]Genetically PWS results from the lack of expression of at least two imprinted genes located in the 15q11-q13 region, the paternal copy of these genes being expressed and their maternal copy being always silenced. It is accepted that PWS is a multigenic syndrome, involving more than one mutated gene (Goldstone 2004). From human genetic studies it has been proposed a role of SNORD116 (encoding for Small Nucleolar Orphan RNAs), in the hyperphagia, obesity and hypogonadism described in PWS (Sahoo, del Gaudio et al. 2008; de Smith, Purmann et al. 2009).
Muscatelli teaches Prader-Willi syndrome is a rare genetic disease, and in humans SNORD116 (encoding for Small Nucleolar Orphan RNAs) plays a role in the hyperphagia, obesity and hypogonadism described in the condition. Muscatelli is generally directed to treating the eating disorder associated with PW, and doesn’t teach treating the symptoms of hypogonadism in the disorder.
Kumar teaches that one symptom of hypogonadism is muscle wasting. Kumar notes that hypogonadism results in low testosterone and results in many symptoms. Kumar states, “Signs of hypogonadism include absence or regression of secondary sex characteristics, anemia, muscle wasting, reduced bone mass or bone mineral density, oligospermia, and abdominal adiposity.”
Given that the art teaches the use of CLA for both muscle wasting and obesity, one would find it obvious to use CLA for its known properties (improving muscle mass and reducing obesity) in PW syndrome (SNORD116 deficiency) because the treatment of the symptoms of the disease would be beneficial to the patient by allowing better physical devolpment while reducing the unwanted outcomes of poor muscle development and the metabolic problems caused by obesity. As such claims 1-3, 5-11 are obvious, and claims 12-14 and 16-21 are anticipated.
In regards to instant claim 4 (see Kim et al. “Conjugated Linoleic Acid: Potential Health Benefits as a Functional Food Ingredient, “Annu. Rev. Food Sci. Technol. 2016. 7:221–44):
Instant claim 4 requires the method of claim 1, wherein the effective amount of the CLA is about 3-10 g/kg body weight per day, optionally about 5 g/kg body weight per day.
The Specification states, “In humans, studies achieving weight loss were dosing at a minimum of 2.8 g/day/kg body mass for at least 4 months. In this study, a Tonalin™ CLA dosing was calculated to be at an equivalent dose of 5.2 g CLA/kg body mass in free-feeding animals (0.13 g total per day). A study of 73 patients (age range 16-58 years), with either deletion of the locus (64%) or uniparental disomy (36%), the average body mass was 99.4 kg and 81.0 kg, respectively, and in the overweight-to-obese range for those individuals [51]. Thus, for an adult individual with PWS at ˜90 kg, a daily dosage of 468 g of CLA would be equivalent in grams CLA/kg body mass. Obviously, this is not achievable or within GRAS guidelines, so dosage of patients with PWS would have to be titrated to find the optimal range for body weight loss.”
Applicant’s statement, “a daily dosage of 468 g of CLA would be equivalent in grams CLA/kg body mass. Obviously, this is not achievable or within GRAS guidelines, so dosage of patients with PWS would have to be titrated to find the optimal range for body weight loss.”
The art of record would not render obvious this dose. As even the lowest end claimed in instant claim 4 is 3 g/kg body weight, in a small human child (50 kg) this would still be 150 grams of CLA.
Looking at review a review article, Kim teaches the highest dose given was 18.9 g/day. This is an order of magnitude lower than instant claim 4.
Given that the dose is not found in the art and the art would find this dose to be unsafe, in combination with the finding by Applicant that this large dose achieved actual weight reductions in this patient population, this dose would be allowable.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL J SCHMITT whose telephone number is (571)270-7047. The examiner can normally be reached M-F 8-6 MidDay Flex.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Lundgren can be reached at 571-272-5541. 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.
/MICHAEL J SCHMITT/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629