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 .
Change of Examiner
The examiner assigned to the instant application has changed. The new examiner is James D. Anderson. Contact information is provided at the end of this Office Action.
Formal Matters
Claims 1-34 were originally presented on 07/15/2022. The preliminary amendments to the claims, also filed on 07/15/2022, have been received and entered. Claims 5-8, 12-13, and 21-33 were cancelled. Claims 1-4, 9-11, 14-20, and 34 were then pending and were subject to a Requirement for Restriction/Election on 09/04/2025.
Applicant’s response and amendments to the claims, filed 10/22/2025, have been received and entered. Claims 1-4, 9-11, and 34 were cancelled and claims 35-41 newly added.
Claims 14-20 and 35-41 are pending.
Election/Restrictions
Applicant’s election of Group III (claims 14-20) and the species: Formula I (specific drug), a diazoxide Choline Controlled-Release (DCCR formulation) (additional drug), Prader-Willi Syndrome (disease), and oral administration (route of administration), in the reply filed on 10/22/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 14-20 and 35-41 read on the elected invention and species and are presently under examination.
Priority
This application is a national phase application claiming benefit of priority under 35 U.S.C. §371 to Patent Convention Treaty (PCT) International Application PCT/US2021/012869, filed January 10, 2021, which claims the benefit of priority under 35 U.S.C. § 119(e) of U.S. Provisional Application Nos. USSN 62/959,534, filed January 10, 2020; USSN 62/959,769, filed January 10, 2020; USSN 62/980,053, filed February 21, 2020; and, USSN 63/022,484, filed May 9, 2020.
Information Disclosure Statement
Applicant’s Information Disclosure Statements filed 7/15/2022, 6/5/2023, 3/12/2024, 4/16/2024, 3/13/2025, 3/30/2025, 6/6/2025, 10/19/2025, and 11/11/2025 have been received and entered into the present application. As reflected by the attached, completed copies of form PTO-1449, the Examiner has considered the cited references to the extent that they comply with the provisions of 37 C.F.R. §1.97, §1.98 and MPEP §609.
Claim Objections
Claims 40-41 are objected to because of the following informalities: the claims recite “…wherein the pharmaceutical composition or dosage form, wherein: the diazoxide…” in lines 1-2 of each respective claim, which is grammatically awkward. The phrase “wherein the pharmaceutical composition or dosage form,” should be removed from claims 40 and 41.
Appropriate correction is required.
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.
"The primary purpose of this requirement of definiteness of claim language is to ensure that the scope of the claims is clear so the public is informed of the boundaries of what constitutes infringement of the patent. A secondary purpose is to provide a clear measure of what applicants regard as the invention so that it can be determined whether the claimed invention meets all the criteria for patentability and whether the specification meets the criteria of 35 U.S.C. 112, first paragraph with respect to the claimed invention.", (see MPEP § 2173).
Claims 14-20 and 35-41 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.
The claims are drawn to a method for treating, ameliorating, slowing the progress of, reducing the symptoms of, reducing adverse events associated with, or preventing, a disease or condition comprising or associated with Prader-Willi Syndrome. See Claim 14.
Prader-Willi Syndrome is a genetic disorder caused by the loss of function of genes in a particular region of chromosome 15. In infancy, this condition is characterized by weak muscle tone (hypotonia), feeding difficulties, poor growth, and delayed development. Beginning in childhood, affected individuals develop an insatiable appetite, which leads to chronic overeating (hyperphagia) and obesity. Some people with Prader-Willi syndrome, particularly those with obesity, also develop type 2 diabetes. In some people with Prader-Willi syndrome, the loss of a gene called OCA2 is associated with unusually fair skin and light-colored hair.
The expression “…treating, ameliorating, slowing the progress of, reducing the symptoms of, reducing adverse events associated with, or preventing, a disease or condition comprising or associated with…Prader-Willi Syndrome…” does not clearly delimit the therapeutic indication(s) intended to be encompassed by the claims. Indeed, the words “…comprising or associated with…Prader-Willi Syndrome…” imply a link between the intended “disease or condition” and Prader-Willi Syndrome but neither the claims nor the specification define such diseases or conditions or how they are “associated with” Prader-Willi Syndrome. Additionally, “symptoms” and “adverse events” associated with Prader-Willi Syndrome are not defined in the claims or specification.
The metes and bounds of the claims are unclear because it is not apparent whether the claims are intended to be limited to administering the claimed compound to individuals actually diagnosed with Prader-Willi Syndrome. For example, as discussed above Type 2 diabetes is a disease “associated with” Prader-Willi Syndrome, i.e., some people Prader-Willi syndrome, particularly those with obesity, also develop type 2 diabetes. The claims could therefore be construed to encompass administering the claimed compound to any individual having Type 2 diabetes or obesity, even if they are not also diagnosed with Prader-Willi Syndrome.
The Examiner suggests amending the preamble of claim 14 to recite “[a] method for treating, ameliorating, slowing the progress of, or reducing the symptoms of…Prader-Willi Syndrome…” so as to clearly and unequivocally convey that the intended subject population of the claims are individuals with Prader-Willi Syndrome.
Claims 18-19 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 18 recites the limitations "the drug” and “therapeutic combination" in lines 3-4 and lines 5-6. Claim 19 recites the limitations “the drug” and “therapeutic combination” in line 5. There is insufficient antecedent basis for this limitation in the claims.
Claims 18 and 19 each depend from claim 16, which itself depends from claim 14. Nowhere does claim 14 or 16 recite a “drug” or “therapeutic combination”, rendering it unclear what drug and therapeutic combination are being referenced in claims 18 and 19.
Claim Rejections - 35 USC § 112(a) (Enablement)
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 14-20 and 35-41 are 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, ameliorating, slowing the progress of, or reducing the symptoms of Prader-Willi Syndrome, does not reasonably provide enablement for preventing a disease or condition associated with Prader-Willi Syndrome. 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 be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993). Explaining what is meant by “undue experimentation,” the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996).1
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1) the quantity of experimentation necessary,
2) the amount of direction or guidance provided,
3) the presence or absence of working examples,
4) the nature of the invention,
5) the state of the prior art,
6) the relative skill of those in the art,
7) the predictability of the art, and
8) the breadth of the claims.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The nature of the invention, and breadth of the claims
The claims are drawn to a method for treating, ameliorating, slowing the progress of, reducing the symptoms of, reducing adverse events associated with, or preventing, a disease or condition comprising or associated with Prader-Willi Syndrome. See Claim 14.
The claims thus broadly encompass treating, ameliorating, slowing the progress of, reducing the symptoms of, reducing adverse events associated with, or preventing, any disease or condition “comprising or associated with” Prader-Willi Syndrome.
Prader-Willi Syndrome is a genetic disorder caused by the loss of function of genes in a particular region of chromosome 15. In infancy, this condition is characterized by weak muscle tone (hypotonia), feeding difficulties, poor growth, and delayed development. Beginning in childhood, affected individuals develop an insatiable appetite, which leads to chronic overeating (hyperphagia) and obesity. Some people with Prader-Willi syndrome, particularly those with obesity, also develop type 2 diabetes. In some people with Prader-Willi syndrome, the loss of a gene called OCA2 is associated with unusually fair skin and light-colored hair.
Applicants disclose that the only therapy currently approved by the United States Food and Drug Administration (FDA) to treat Prader-Willi Syndrome (PWS) is human growth hormone, which is used to increase linear growth. There are no therapies approved to treat the hallmark features of PWS, specifically hyperphagia, anxiety, and obsessive and compulsive symptoms. There is no approved pharmaceutical treatment for hyperphagia or associated behavioral symptoms associated with PWS. Specification at p.2, l.13-18.
The state and predictability of the art, and relative skill of those in the art
As discussed above, while human growth hormone is approved to increase linear growth in subjects having Prader-Willi Syndrome, there are no therapies approved to treat the hallmark features of PWS, specifically hyperphagia, anxiety, and obsessive and compulsive symptoms. Being a genetic disorder, there is no known therapy effective to prevent Prader-Willi Syndrome, nor is there any known therapy effective to prevent symptoms and adverse events associated with Prader-Willi Syndrome, e.g., obesity, hyperphagia, anxiety, type 2 diabetes, etc.
The claimed compound of Formula I was known in the art (US 2010/0292243 A1) where it is disclosed as an “triple inhibitor” of the monoamines DAT, NET, and SERT and therefore useful in the treatment of various neurological and physiological disorders. US ‘243 describes animal behavioral assays (Mouse Tail Suspension Assay, Rat Forced Swim Assay, and Rat and Mouse Locomotor Activity) but the activity of the compound of Formula I in these assays is not provided other than a statement that the minimum effective dose of Example 1-(+)-enantiomer in the mouse tail suspension study was 10 mg/kg. No therapeutic activity of the compound of Formula I in any model of any disease or disorder is provided.
As illustrative of the state of the art, the examiner cites BUTLER ET AL. (Current Pediatric Reviews, 2019, 15, 207-244). Butler et al. teach that disorders “associated with” Prader-Willi syndrome include, inter alia, orthopedic problems (e.g., hip dysplasia, growth hormone deficiency, osteroporosis and osteopenia), hypothyroidism and central adrenal insufficiency, increased risk of seizures, temperature instability, dry mucosal membranes and decreased salivary flow, adenotonsillar hypertrophy, obesity, craniofacial abnormalities and neuromuscular weakness (p.212). They teach that there is no recognized approach to prevent the risk of lowering the chance of having a child with Prader-Willi syndrome (p.213, paragraph bridging left and right columns). They teach that there is a paucity of evidence-based data supporting the use of medical approaches documented for PWS (p.224, left column). Indeed, they teach that “[n]o single medication is available to treat or cure this genetic disorder” (Id.). Medications can be helpful to manage the obesity-related complications associated with PWS, but to date, there is no medication that has successfully managed the drive for food acquisition (p.224, right column). This article plainly demonstrates that the art of treating, let alone preventing, Prader-Willi syndrome is extremely unpredictable.
Thus, at the time the application was filed the claimed compound was known in the art as an “triple inhibitor” of DAT, NET, and SERT uptake but there was no evidence of its therapeutic activity in treating any disease or condition in any subject.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation’.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)” (emphasis added). The “make and use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” The principle was explicitly affirmed most recently in Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008). See also In re Cortright, 49 USPQ2d 1464, 1466 and Bristol-Myers Squibb Co. v. Rhone-Poulenc Rorer Inc., 49 USPQ2d 1370.
The relative skill of those in the art is high, generally that of an M.D. or Ph.D. That factor is outweighed, however, by the unpredictable nature of the art of treating Prader-Willi syndrome with a single medication as claimed.
It is well established that "the scope of enablement varies inversely with the degree of unpredictability of the factors involved” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 166 USPQ 18, at 24 (In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved.), Nationwide Chemical Corporation, et al. v. Wright, et al., 192 USPQ 95 (one skilled in chemical and biological arts cannot always reasonably predict how different chemical compounds and elements might behave under varying circumstances), Ex parte Sudilovsky 21 USPQ 2d 1702 (Appellant's invention concerns pharmaceutical activity. Because there is no evidence of record of analogous activity for similar compounds, the art is relatively unpredictable) In re Wright 27 USPQ2d 1510 (the physiological activity of RNA viruses was sufficiently unpredictable that success in developing specific avian recombinant virus vaccine was uncertain). As long as the Specification discloses at least one method of making and using the claimed invention that bears a reasonable correlation to the entire scope of the claim, then the enablement requirement of 35 U.S.C. 112, 1st Paragraph is satisfied. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). To that extent, if little is known in the prior art about the nature of the invention and the art is unpredictable, the Specification would need more detail as to how to make and use the invention in order to be enabling. See Chiron Corp v. Genetech, lnc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1326 (Fed. Cir. 2004) ("Nascent technology, however, must be enabled with a specific and useful teaching. The law requires an enabling disclosure for nascent technology because a person of ordinary skill in the art has little or no knowledge independent from the patentee's instruction. Thus, the public's end of the bargain struck by the patent system is a full enabling disclosure of the claimed technology.")
Here, there is no evidence in the art of analogous activity for similar compounds being effective in treating, let alone preventing, diseases or conditions “comprising or associated with” Prader-Willi syndrome. As will be discussed in more detail below, the Specification lacks any evidence of therapeutic activity of the claimed compound in treating, let alone preventing, a disease or condition comprising or associated with Prader-Willi syndrome.
These factors therefore weigh against enablement for the full scope of the claimed invention.
The amount of direction or guidance provided and the presence or absence of working examples
Example 1 of the disclosure describes a therapeutic protocol for treatment of Prader-Willi syndrome by administering Formula I or a deuterated analogue thereof comprising choosing patients with documented medical record history of PWS and administering a pharmaceutical composition comprising Formula I to achieve a target dose needed to achieve dopamine transporter (DAT occupancy of between 15% to 75%. No patients were actually treated and no evidence of therapeutic activity of a compound of Formula I is provided.
Indeed, there are no working examples demonstrating that the claimed compound of Formula I is therapeutically active in treating any disease or condition in any subject. Rather, the compound is shown to inhibit SERT, DAT, and NET at concentrations of 10 nM and 100 nM in vitro (Example 13) and pharmacokinetics are determined for the compound in healthy human subjects (Example 20).
The quantity of experimentation necessary
Because of the known unpredictability of the art (as discussed supra) and in the absence of experimental evidence commensurate in scope with the claims, the skilled artisan would not accept the assertion that the instantly claimed compound could be predictably used to prevent a disease or condition associated with Prader-Willi Syndrome as inferred in the claims and contemplated by the specification.
Genentech Inc. vs. Nova Nordisk states, "[A] patent is not a hunting license. It is not a reward for a search but a compensation for its successful conclusion and ‘patent protection’ is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable” (42 USPQ 2d 1001, Fed. Circuit 1997).
In the instant case, Applicants have presented a general idea that because the instantly claimed compound is a triple inhibitor of monoamine uptake it must therefore, a priori, be useful in the treatment and prevention of any disease or condition comprising or associated with Prader-Willi Syndrome. However, given the fact that there is no recognized approach to prevent the risk of lowering the chance of having a child with Prader-Willi syndrome and “[n]o single medication is available to treat or cure this genetic disorder” (Butler et al.), a person of ordinary skill in the art would have no expectation of success in preventing a disease or condition associated with Prader-Willi Syndrome by administering a compound of Formula I to an individual.
Accordingly, the instant claims do not comply with the enablement requirement of 35 U.S.C. § 112, first paragraph, since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
The Examiner suggests amending the preamble of claim 14 to recite “[a] method for treating, ameliorating, slowing the progress of, or reducing the symptoms of…Prader-Willi Syndrome…”.
Conclusion
Claims 14-20 and 35-41 are rejected.
Claims 40-41 are objected to.
No claims are allowed.
Applicant is requested to specifically point out the support for any amendments made to the disclosure in response to this Office action, including the claims (M.P.E.P. §§ 714.02 and 2163.06). In doing so, applicant is requested to refer to pages and line (or paragraph) numbers (if available) in the as-filed specification, not the published application. Due to the procedure outlined in M.P.E.P. § 2163.06 for interpreting claims, other art may be applicable under 35 U.S.C. § 102 or 35 U.S.C. § 103(a) once the aforementioned issue(s) is/are addressed.
Applicant is reminded that MPEP §2001.06(b) clearly states that “[t]he individuals covered by 37 C.F.R. 1.56 have a duty to bring to the attention of the examiner, or other Office official involved with the examination of a particular application, information within their knowledge as to other copending United States applications which are "material to patentability" of the application in question." See Armour & Co. v. Swift & Co., 466 F.2d 767, 779, 175 USPQ 70, 79 (7th Cir. 1972). MPEP §2001.06(b) clearly indicates that “if a particular inventor has different applications pending in which similar subject matter but patentably indistinct claims are present that fact must be disclosed to the examiner of each of the involved applications.” See Dayco Prod. Inc. v. Total Containment, Inc., 329 F.3d 1358, 1365-69, 66 USPQ2d 1801, 1806-08 (Fed. Cir. 2003).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAMES D ANDERSON whose telephone number is (571)272-9038. The examiner can normally be reached on Monday-Friday, 7:30 am - 4:00 pm PST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Lundgren can be reached on 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 an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/James D. Anderson/Primary Examiner, Art Unit 1629
UNITED STATES PATENT AND TRADEMARK OFFICE
500 Dulany Street
Alexandria, VA 22314-5774
Tel. No.: (571) 272-9038
1 As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is “undue”, not “experimentation”.