DETAILED ACTION
Claims 1-14 and 16-21 were pending. Claims 1 and 12 have been amended; claim 17 has been canceled; and claim 41 is newly added via the Reply of 6/26/2026.
Claims 1-3, 5-14, 16, 18-21, and 41 are pending and the Subject of the Office Action below.
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.
Claim Rejections - 35 USC § 112
(New Rejection, required by an amendment)
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 5 and 16 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. Claims 5 and 16 both require, “wherein the CLA or formulation thereof comprises a mixture of CLA isoforms, optionally a 50:50 mixture of trans-10, cis-12 and trans9, cis-11 CLA isomers.” The claims they are dependent to require, “wherein at least 80% by weight of the CLA or formulation thereof consists of trans-10, cis-12 and cis-9, trans-11 CLA isomers in a 50:50 ratio.” Therefore the dependent claims do not further limit. 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
(New Rejection, required by an amendment)
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, 16, 18-21, and 41 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cho INNOBIO Gras submission 5/12/2014.
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, and wherein at least 80% by weight of the CLA or formulation thereof consists of trans-10, cis-12 and cis-9, trans-11 CLA isomers in a 50:50 ratio.
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.
Cho teaches CLA 95 FFA. Cho states, “with approximately 95% (93-97%) CLA in FFA form. It has a 1:1 ratio of the c9,t11 and t10,c12 isomers, derived from 100% pure, natural safflower seed oil with molecular distillation process.” Cho states, “consists of approximately 95% (93-97%) total CLA isomers and at least 88% of a 1:1 mixture of c9,t11 and t10,c12 CLA isomers. The remaining oil consists of other fatty acids, such as linoleic, oleic, palmitic, and stearic.”
Cho teaches the formulation in Table 1-6:
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468
700
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Greyscale
Cho teaches that CLA can be used in a variety of effective amounts. Claim 14 states, “wherein (a) the effective amount of CLA is at least 1,000 mg per day, optionally about 3,000 to about 5,000 mg per day, (b) the effective amount of CLA is about 3-10 g/kg body weight per day, optionally about 5 g/kg body weight per day, or (c) both (a) and (b).” This doesn’t require any changes to the product and is just a statement of informed dose of the intended use and is therefore anticipated by the product itself.
Claim 16 is not further limiting.
Claim 18 requires, “wherein the effective amount of CLA decreases body weight, decreases fat mass, increases lean body mass, improves hypogonadism or a symptom thereof, improves testicular morphology, modulates the a-diversity of the gut microbiome, modulates hypothalamic gene expression of one or more genes, decreases anxiety, increase sperm maturation, increase spermatogenesis, increase sperm differentiation, U.S. Patent Application No. 18/289,409 decrease testicular degeneration or any combination thereof in the subject in need thereof.” This again is a states property of the CLA when administered, given this is a product claim, this does not require any structural change and is anticipated by the product of Cho.
Claim 19 requires, “wherein the dietary supplement, feed, or foodstuff or beverage formulation is a liquid, solid, semi-solid, or an emulsion.” Cho states the product is a liquid.
Claim 20 requires, “wherein the dietary supplement, feed, or foodstuff or beverage formulation is adapted for daily, every other day, weekly, or monthly administration.” The oil/liquid could be used this way, and therefore anticipated the claim.
Claim 21 requires, “wherein the subject in need thereof is a mammal, optionally a human.” Cho teaches the use in animals and humans.
Claim 41 requires, “wherein at least 90% by weight of the CLA or formulation thereof consists of trans-10, cis-12 and cis-9, trans-11 CLA isomers in a 50:50 ratio.” Cho teaches that the CLA total is 93-97% and the two isomers is 88% min, resulting in the percentage of CLA to be 90.7% to 94.6% the two isomers. Thereby this claim is anticipated.
Claims 12-14, 16, 18-21, and 41 are anticipated.
Claim Rejections - 35 USC § 103
(New Rejection, required by an amendment)
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; Slim Down CLA 95 USP Information 2005; 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, and wherein at least 80% by weight of the CLA or formulation thereof consists of trans-10, cis-12 and cis-9, trans-11 CLA isomers in a 50:50 ratio.
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 CLA including Jamieson Slim Down CLA 95 (claim 76) and from about 2.0 g to about 4.0 g per day (claim 86). Moritz doesn’t teach what Jamieson Slim Down CLA 95 is or treating a symptom of Snord116 deficiency.
Slim Down CLA 95 USP contains 950 mg or a 50:50 mix of the two isomers, and 50 mg of other CLA. Meeting the limitations of the requires percentages.
The USP 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 development 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, 16, 18-21, and 41 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.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 nonprovisional extension fee (37 CFR 1.17(a)) 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.
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.
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/MICHAEL J SCHMITT/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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