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 .
Election/Restrictions
Applicant’s election without traverse of the species
Oxytocin receptor agonist: oxytocin
Genetic developmental disorder: Prader-Willi syndrome and Prader-Willi like syndromes
in the reply filed on June 17, 2026, is acknowledged.
Claim 27 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected genetic developmental disorder species, there being no allowable generic or linking claim.
Claim Objections
Claim 29 is objected to because of the following informalities: experimented, experiments, and experimenting should be experienced, experiences, and experiencing. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 19-26, 28-33, and 35-38 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating or delaying the onset of dysphagia in subjects with Prader-Willi syndrome with oxytocin, does not reasonably provide enablement for treating or delaying the onset of dysphagia in any other subjects or using any other oxytocin receptor agonist. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
To comply with the enablement requirements of 35 U.S.C. §112, first paragraph, a specification must adequately teach how to make and how to use a claimed invention throughout its scope, without undue experimentation. Plant Genetic Systems N.V. v. DeKalb Genetics Corp., 315 F.3d 1335, 1339, 65 USPQ2d 1452, 1455 (Fed. Cir. 2003). There are a variety of factors which may be considered in determining whether a disclosure would require undue experimentation. These factors include:
The Nature of the Invention
The invention pertains to the use of oxytocin receptor agonists to treat and delay the onset of dysphagia in patients with autonomic nervous system dysfunction and neurodevelopmental disorders.
The breadth of the claims
The breadth of the genus “oxytocin receptor agonist” includes any molecule of any structure capable of activating the oxytocin receptor in a manner sufficient to treat and delay the onset of dysphagia in patients with autonomic nervous system dysfunction and neurodevelopmental disorders.
The breadth of the patient population in claims 19 and 33 includes subjects with any type of autonomic nervous system dysfunction and neurodevelopmental disorder, respectively.
Only claim 34 is limited to single compound, oxytocin, and patient population, Prader-Willi syndrome or Prader-Willi like disorder.
The State of the Prior Art
The prior art discloses a limited embodiment of the invention. Tauber et al. (The Use of Oxytocin to Improve Feeding and Social Skills in Infants With Prader–Willi Syndrome. Pediatrics, 2017-02, Vol.139 (2): e20162976; hereafter “Tauber”) teaches that patients with Prader–Willi syndrome (PWS) display poor feeding (p 2 col 2). Tauber conducted a phase 2 escalating dose study of a short course (7 days) of intranasal oxytocin (OXT) administration in infants under 6 months old (p 2 col 3; Fig 1). The infants received 4 IU of OXT either every other day, daily, or twice daily (Fig 1). Sucking assessed by the Neonatal Oral-Motor Scale was abnormal in all infants at baseline and normalized in 88% after treatment (p 5 col 2). The scores of Neonatal Oral-Motor Scale and videofluoroscopy of swallowing significantly decreased from 16 to 9 (P < .001) and from 18 to 12.5 (P < .001), respectively (p 5 col 2). Tauber conclude that OXT is well tolerated in infants with PWS and improves feeding and social skills (p 6 col 3). The prior art does not teach other oxytocin receptor agonists for this purpose nor does it teach treating dysphagia associated with other conditions using oxytocin.
The Predictability or Unpredictability of the Art
The prior art pertaining to the treatment of dysphagia is highly unpredictable. In a blog post by the Foundation for Prader-Willi Research from 2019, the level of unpredictability associated with using oxytocin and its analog carbetocin in treating Prader-Willi Syndrome symptoms more broadly and not focused specifically on dysphagia:
Altogether, these studies add to the growing knowledge of oxytocin for PWS, they are also a reminder that there remain significant limitations in understanding how best to use oxytocin or carbetocin in PWS. For example, are the beneficial effects really confined to younger children, or is the lack of improvement seen in older children reflective of small sample size, or dosing and duration that isn’t appropriate for this age group? In addition, although there appears to be some benefits in the younger children, the response is still quite variable. Parents whose children responded positively to oxytocin therapy were enthusiastic about the improvement, but not all families report improvements.
It is still unclear what might separate those seeing benefit from those who don’t. Some possible explanations related to this:
Genetic reasons: Baseline oxytocin levels, oxytocin receptor variants (which are known to influence responsiveness in the normal population) and expression differences, or differences in overall hormone processing unique to PWS (see study below).
Metabolic or environmental factors: Are there certain medications that improve or interfere with beneficial effects of oxytocin? Do behavioral methods or certain environmental factors strengthen or diminish the biological effects of oxytocin?
Dosing: Dosing is challenging with oxytocin, and it's possible that administering too much oxytocin will negate a positive effect or cause a negative response in PWS.
Outcome measures: Are the assessments of changes in social interaction, anxiety and food behavior used in previous studies adequately capturing the changes so that they “show up” in rigorous statistical analyses? Looking ahead, it’s clear that additional, validated measures to capture anxiety, social and food behavior changes across age groups is a priority, as is the ability to accurately quantify the level of oxytocin (active form) in the blood.
Given the high degree of unpredictability in this art, it is incumbent on Applicant to provide description in the specification commensurate with the full scope of the claims.
The Level of Guidance in the Specification
The guidance provided in the specification with respect to administration and dosage is generic.
The level of guidance in the specification is insufficient to determine which of the countless species encompassed by the claim can be used in the claimed method. The specification does not describe a general correlation between structure and function for the claimed genus. The specification does not describe how the oxytocin receptor can be targeted effectively to treat dysphagia in patients other than those suffering from Prader-Willi Syndrome.
The Presence or Absence of Working Examples
The specification discloses the actual reduction to practice of oxytocin for treatment of dysphagia associated with Pradi-Willi syndrome. This embodiment is not representative of the full scope of the claims which include all other oxytocin agonists and all other neurodevelopmental disorders.
The Quantity of Experimentation Necessary
Considering the factors above, the skilled artisan would be burdened with undue experimentation in determining if one of the claimed oxytocin agonists would be effective at treating or delaying the onset of dysphagia in patients with neurodevelopmental disorders. The experimentation required represents years of inventive effort. When the above factors are weighed, it is the examiner's position that one skilled in the art could not practice the invention without undue experimentation.
Therefore, in view of the Wands factors, the claims appear to require undue experimentation to use the full scope of the claimed invention.
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 19-21, 24-26, 28-34, and 38 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tauber et al. (The Use of Oxytocin to Improve Feeding and Social Skills in Infants With Prader–Willi Syndrome. Pediatrics, 2017-02, Vol.139 (2): e20162976; hereafter “Tauber”).
Tauber teaches that patients with Prader–Willi syndrome (PWS) display poor feeding (p 2 col 2). Tauber conducted a phase 2 escalating dose study of a short course (7 days) of intranasal oxytocin (OXT) administration in infants under 6 months old (p 2 col 3; Fig 1). The infants received 4 IU of OXT either every other day, daily, or twice daily (Fig 1). Sucking assessed by the Neonatal Oral-Motor Scale was abnormal in all infants at baseline and normalized in 88% after treatment (p 5 col 2). The scores of Neonatal Oral-Motor Scale and videofluoroscopy of swallowing significantly decreased from 16 to 9 (P < .001) and from 18 to 12.5 (P < .001), respectively (p 5 col 2). Tauber conclude that OXT is well tolerated in infants with PWS and improves feeding and social skills (p 6 col 3).
Regarding claim 19, Tauber teaches a method for treating dysphagia in a subject suffering from an autonomic nervous system dysfunction, infants with Prader-Willi syndrome displaying poor feeding characterized by abnormal sucking and swallowing, comprising administering an oxytocin receptor agonist, oxytocin, to the subject (p 2 col 3; Fig 1). The administration of oxytocin was effective to improve swallowing (i.e. dysphagia) as shown by the decrease in scores of Neonatal Oral-Motor Scale and videofluoroscopy of swallowing (p 5 col 2).
Regarding claim 20, Tauber teaches that at baseline, 13 infants out of 16 displayed pharyngeal stasis that can drive inhalation, whereas only 2 infants displayed it after OXT treatment (p 5 col 2). Tauber teaches that OXT improves oral motor function of the face and head, including the larynx and pharynx (p 7 col 1).
Regarding claim 21, the infant is swallowing liquid (p 2 col 3).
Regarding claims 24-26, the subject has Prader-Willi syndrome (p 2 col 3; Fig 1).
Regarding claim 28, Tauber teaches that at baseline, 13 infants out of 16 displayed pharyngeal stasis that can drive inhalation, whereas only 2 infants displayed it after OXT treatment (p 5 col 2).
Regarding claim 29, Tauber teaches that the infants are at risk of life-threatening aspiration (p 2 col 3).
Regarding claim 30, the oxytocin receptor agonist is oxytocin (p 2 col 3; Fig 1).
Regarding claims 31-32, the infants received 4 IU of OXT either every other day, daily, or twice daily (p 2 col 3; Fig 1), which falls in the claimed range of a daily dosage of 2 IU to 50 IU. An oxytocin dose of 4 IU is 7 mg1, which falls within the claimed range of daily dose of less than 500 mg.
Regarding claim 33, Tauber teaches a method for treating dysphagia in a subject suffering from an autonomic nervous system dysfunction, infants with Prader-Willi syndrome displaying poor feeding characterized by abnormal sucking and swallowing, comprising administering an oxytocin receptor agonist, oxytocin, to the subject (p 2 col 3; Fig 1). The administration of oxytocin was effective to improve swallowing (i.e. dysphagia) as shown by the decrease in scores of Neonatal Oral-Motor Scale and videofluoroscopy of swallowing (p 5 col 2).
Regarding claims 34, the subject has Prader-Willi syndrome (p 2 col 3; Fig 1).
Regarding claim 38, the infants received 4 IU of OXT either every other day, daily, or twice daily, which falls in the claimed range of a daily dosage of 2 IU to 48 IU.
Claims 19, 21-26, and 28-28 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kuppens et al. (Promising effects of oxytocin on social and food-related behaviour in young children with Prader-Willi syndrome: a randomized, double-blind, controlled crossover trial. Clin Endocrinol (Oxf). 2016 Dec;85(6):979-987; hereafter “Kuppens”).
Claim Interpretation: BRI of “treating or delaying the onset of dysphagia” includes preventing, which further includes administering to subjects at risk of dysphagia. Because PWS patients are at risk of dysphagia, the claims include treating PWS patients with oxytocin.
Kuppens reports a clinical trial to evaluate the effects of intranasal oxytocin compared to placebo administration on social behavior and hyperphagia in children with PWS. The subjects, children with PWS (aged 6 to 14 years), received twice daily intranasal oxytocin (dose range 24-48 IU/day) for four weeks (p 980 col 2). Kuppens teaches that intranasal oxytocin administration has beneficial effects on social behavior and food-related behavior in children with PWS younger than 11 years of age, but not in those older than 11 years of age (p 985 col 1).
Regarding claim 19, Kuppens reports a clinical trial to evaluate the effects of intranasal oxytocin compared to placebo administration on social behavior and hyperphagia in children with PWS. The subjects, children with PWS (aged 6 to 14 years), received twice daily intranasal oxytocin (dose range 24-48 IU/day) for four weeks (p 980 col 2).
MPEP § 2112.02(II) states: [W]hen the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978)
In the instant case, the claim encompasses a method of administering oxytocin to a subject with PWS. The result of the claimed method, as expressed in the preamble of the claim is treating or delaying the onset of dysphagia. The prior art teaches a method of administering twice daily intranasal oxytocin (dose range 24-48 IU/day) to children with PWS (aged 6 to 14 years) but is silent as to the effect on delaying the onset of dysphagia. Because the prior art teaches all of the same active method steps as the claim, that is administering the same exact structure, to the same patients, in the same manner, the claimed effect of delaying the onset of dysphagia is inherent to the prior art method. The inventors have found a new property of oxytocin and such a discovery does not constitute a new use.
Therefore, Kuppens anticipates claim 19.
Regarding claim 21, children with PWS (aged 6 to 14 years) eat both solids and liquids.
Regarding claims 22-23, Kuppens teaches that the subjects are aged 6 to 14 years (p 980 col 2), which falls within the claimed ranges/categories.
Regarding claims 24-26, the subject has Prader-Willi syndrome (p 980 col 2).
Regarding claims 28-29, the claim encompasses a method of administering oxytocin to a subject with PWS. The result of the claimed method, as expressed in the preamble of the claim is treating or delaying the onset of dysphagia, wherein the dysphagia has certain features as outlined in claim 28 and wherein the patient is at risk of certain effects of dysphagia as outlined in claim 29. The prior art teaches a method of administering twice daily intranasal oxytocin (dose range 24-48 IU/day) to children with PWS (aged 6 to 14 years) but is silent as to the effect on delaying the onset of dysphagia. Because the prior art teaches all of the same active method steps as the claim, that is administering the same exact structure, to the same patients, in the same manner, the claimed effect of delaying the onset of dysphagia with the features and risks of claims 28-29 is inherent to the prior art method. The inventors have found a new property of oxytocin and such a discovery does not constitute a new use.
Regarding claim 30, the oxytocin receptor agonist is oxytocin (p 980 col 2).
Regarding claims 31-32, the subjects received 4 IU of OXT twice daily (p 980 col 2), which falls in the claimed range of a daily dosage of 2 IU to 50 IU. An oxytocin dose of 4 IU is 7 mg2, which falls within the claimed range of daily dose of less than 500 mg.
Regarding claim 33, Kuppens reports a clinical trial to evaluate the effects of intranasal oxytocin compared to placebo administration on social behavior and hyperphagia in children with PWS. The subjects, children with PWS (aged 6 to 14 years), received twice daily intranasal oxytocin (dose range 24-48 IU/day) for four weeks (p 980 col 2).
The claim encompasses a method of administering oxytocin to a subject with PWS. The result of the claimed method, as expressed in the preamble of the claim is treating or delaying the onset of dysphagia. The prior art teaches a method of administering twice daily intranasal oxytocin (dose range 24-48 IU/day) to children with PWS (aged 6 to 14 years) but is silent as to the effect on delaying the onset of dysphagia. Because the prior art teaches all of the same active method steps as the claim, that is administering the same exact structure, to the same patients, in the same manner, the claimed effect of delaying the onset of dysphagia is inherent to the prior art method. The inventors have found a new property of oxytocin and such a discovery does not constitute a new use.
Regarding claims 34, the subject has Prader-Willi syndrome (p 980 col 2).
Regarding claims 35-36, Kuppens teaches that the subjects are aged 6 to 14 years (p 980 col 2), which falls within the claimed ranges/categories.
Regarding claim 37, subjects with Prader-Willi syndrome are at risk of subclinical dysphagia, as evidenced by the specification at pp 9-10, bridging para.
Regarding claim 38, the subjects received 4 IU of OXT twice daily (p 980 col 2), which falls in the claimed range of a daily dosage of 2 IU to 48 IU.
Claims 19, 21-26, and 28-28 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Muscatelli et al. (U.S. Patent No. 9,125,862 B2, published September 8, 2015; hereafter “Muscatelli”).
Claim Interpretation: BRI of “treating or delaying the onset of dysphagia” includes preventing, which further includes administering to subjects at risk of dysphagia. Because PWS patients are at risk of dysphagia, the claims include treating PWS patients with oxytocin.
Muscatelli reports a clinical trial to evaluate the effects of intranasal oxytocin in adults with PWS. The subjects, adults with PWS, received 24 IU of intranasal oxytocin (Example 2).
Regarding claim 19, Muscatelli reports a clinical trial to evaluate the effects of intranasal oxytocin in adults with PWS. The subjects, adults with PWS, received 24 IU of intranasal oxytocin (Example 2).
MPEP § 2112.02(II) states: [W]hen the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978)
In the instant case, the claim encompasses a method of administering oxytocin to a subject with PWS. The result of the claimed method, as expressed in the preamble of the claim is treating or delaying the onset of dysphagia. The prior art teaches a method of administering24 IU intranasal oxytocin to adults with PWS but is silent as to the effect on delaying the onset of dysphagia. Because the prior art teaches all of the same active method steps as the claim, that is administering the same exact structure, to the same patients, in the same manner, the claimed effect of delaying the onset of dysphagia is inherent to the prior art method. The inventors have found a new property of oxytocin and such a discovery does not constitute a new use.
Therefore, Muscatelli anticipates claim 19.
Regarding claim 21, adults with PWS eat both solids and liquids.
Regarding claims 22-23, Muscatelli teaches that the subjects are adults (Example 2), which falls within the claimed ranges/categories.
Regarding claims 24-26, the subject has Prader-Willi syndrome (Example 2).
Regarding claims 28-29, the claim encompasses a method of administering oxytocin to a subject with PWS. The result of the claimed method, as expressed in the preamble of the claim is treating or delaying the onset of dysphagia, wherein the dysphagia has certain features as outlined in claim 28 and wherein the patient is at risk of certain effects of dysphagia as outlined in claim 29. The prior art teaches a method of administering 24 IU intranasal oxytocin to adults with PWS but is silent as to the effect on delaying the onset of dysphagia. Because the prior art teaches all of the same active method steps as the claim, that is administering the same exact structure, to the same patients, in the same manner, the claimed effect of delaying the onset of dysphagia with the features and risks of claims 28-29 is inherent to the prior art method. The inventors have found a new property of oxytocin and such a discovery does not constitute a new use.
Regarding claim 30, the oxytocin receptor agonist is oxytocin (Example 2).
Regarding claims 31-32, the subjects received 24 IU of oxytocin in one day (Example 2), which falls in the claimed range of a daily dosage of 2 IU to 50 IU. An oxytocin dose of 24 IU is 40 mg3, which falls within the claimed range of daily dose of less than 500 mg.
Regarding claim 33, Muscatelli reports a clinical trial to evaluate the effects of intranasal oxytocin in adults with PWS. The subjects, adults with PWS, received 24 IU of intranasal oxytocin (Example 2).
The claim encompasses a method of administering oxytocin to a subject with PWS. The result of the claimed method, as expressed in the preamble of the claim is treating or delaying the onset of dysphagia. The prior art teaches a method of administering 24 IU intranasal oxytocin to adults with PWS but is silent as to the effect on delaying the onset of dysphagia. Because the prior art teaches all of the same active method steps as the claim, that is administering the same exact structure, to the same patients, in the same manner, the claimed effect of delaying the onset of dysphagia is inherent to the prior art method. The inventors have found a new property of oxytocin and such a discovery does not constitute a new use.
Regarding claims 34, the subject has Prader-Willi syndrome (Example 2).
Regarding claims 35-36, Kuppens teaches that the subjects are adults (Example 2), which falls within the claimed ranges/categories.
Regarding claim 37, subjects with Prader-Willi syndrome are at risk of subclinical dysphagia, as evidenced by the specification at pp 9-10, bridging para.
Regarding claim 38, the subjects received 24 IU of oxytocin in one day (Example 2), which falls in the claimed range of a daily dosage of 2 IU to 48 IU.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA M MARCHETTI BRADLEY whose telephone number is (571)272-9044. The examiner can normally be reached Monday-Friday, 8:30 am - 5 pm.
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, Lianko G Garyu can be reached at (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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CHRISTINA M MARCHETTI BRADLEY
Primary Examiner
Art Unit 1654
/CHRISTINA M MARCHETTI BRADLEY/ Primary Examiner, Art Unit 1654
1 IU to mass conversion for oxytocin is reported at https://www.seekpeptides.com/blog/articles/oxytocin-peptide-dosage-chart
2 IU to mass conversion for oxytocin is reported at https://www.seekpeptides.com/blog/articles/oxytocin-peptide-dosage-chart
3 IU to mass conversion for oxytocin is reported at https://www.seekpeptides.com/blog/articles/oxytocin-peptide-dosage-chart
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