DETAILED ACTION
Status of the Application
Receipt is acknowledged of Applicant’s Amendments and Remarks, filed 5 December 2025, in the matter of Application N° 18/252,873. Said documents have been entered on the record. The Examiner further acknowledges the following:
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-4 and 17 has been canceled.
Claims 5, 11, 16, 18, 20, 21, and 27 have been amended. Claims 16 and 27 have been amended to change their dependencies to claim 5. Claims 18, 20, and 21 have been editorially amended. Claim 5 has been amended to add the limitations of canceled claim 1 and 17 to the composition as well as the Cmax >4-hr release property. The property is supported by the previously rejected claims (see claim 26(ii)).
Claim 11 has been amended to replace the tradenames Eudragit RL and Eudragit RS with their generic, IUPAC names.
Claim 28 has been added.
No new matter has been added.
Thus, claims 5-16, 18, and 20-28 now represent all claims currently under consideration.
Information Disclosure Statement
One new Information Disclosure Statement (IDS) filed 5 December 2025 is acknowledged and has been considered.
Withdrawn Rejections
Rejection under 35 USC 112
Applicant’s amendment to claim 11 is sufficient in overcoming the previously raised indefiniteness rejection. Said rejection is withdrawn.
Maintained Rejections
The following rejections are maintained from the previous Office Correspondence dated 5 June 2025 since the art that was previously cited continues to read on the amended and previously recited limitations.
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 5-9, 11, 12, 16, and 22-28 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Dohil (WO 2018/093364 A1). [emphasis added to reflect canceled/added claims]
The instantly claimed invention is directed to an oral composition comprising cystamine or a pharmaceutically acceptable salt (i.e., cystamine dihydrochloride) and one or more pharmaceutically acceptable carriers, diluents, or carriers.
Dohil discloses a pharmaceutical dosage form comprising a tablet wherein said tablet comprises a core of a cystamine salt, such as cystamine dihydrochloride, and has an enteric coating (see e.g., claims 1 and 12). The core is further taught as comprising a binder (see e.g., claim 10). Disclosure of the enteric coating is considered to read on the instantly recited limitation of “one or more time-release coatings,” as well as the limitation of “one or more functional coatings.” Claim 44 of the reference discloses that the enteric coating is Eudragit, which is further defined as including both the “RL” and “RS” blends (see ¶[0043]).
Paragraphs [0022] and [0028] add to the definition of a “tablet” stating that it refers to a mixture of active substances and excipients, wherein the excipients can include, in addition to a binder, fillers, disintegrants, lubricants, glidants, and combinations thereof.
The foregoing is considered to read on the limitations of claims 5-9, 11, 12, 26, and 27.
Regarding the limitations of claims 5, 12, and 26, the Examiner acknowledges that the “large intestine release (LIR)” designation of the claimed composition means that it is intended that the formulation releases in the large intestine. However, the positively recited limitations are expressly met by the disclosure of Dohil. Such defining limitations include: “time-release coating,” “functional coating,” and “Eudragit® RL,” or “RS” coatings, all of which are recited as and disclosed as surrounding a cystamine tablet core.
Regarding the limitations presented in claims 22 and 23, the Examiner acknowledges that the limitations are directed to properties that are associated with administering the composition of claim 1, as recited by claim 16. Since the limitations of the administered composition are expressly disclosed, the Examiner advances, absent a showing of evidence to the contrary, that the recited properties are similarly met.
MPEP §2112.01(I) states that “[w]here the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not.”
In the instant case, the Examiner has provided Applicants with an express showing of the claimed compositions.
Regarding the “kit” recited by claim 27, the Examiner submits that the compositional merits which would be considered to contribute to any patentability of the claim are directed to the composition, and not the instructions component of the claim. The compositional elements of the claim are indistinct from those recited by claim 1, thereby rendering the claim anticipated. See MPEP §2112.01(III) regarding nonfunctional printed matter.
The limitations of claims 16, 17, 24, and 25 are disclosed as well (see e.g., Abstract; claims; ¶[0061]).
The reference is thus considered to anticipate the claimed inventions.
Response to Arguments
Applicant’s amendments and arguments with regard to the rejection of claims 5-9, 11, 12, 16, and 22-28 under pre-AIA 35 USC 102(a)(1)/(a)(2) as being anticipated by Dohil have been fully considered, but are not persuasive.
Applicant’s remarks acknowledges that the reference discloses coating the practiced formulations with enteric coatings and that the definition of said coating(s) includes both Eudragit® RL and RS polymers. Applicant also argues that the practiced compositions are directed to formulations that are completely different than the formulations that are instantly claimed.
Applicant emphasizes that the instantly claimed compositions are intended to provide large intestinal release (LIR) and provide a definition for enteric coatings noting, per the cited reference, that such a coating is defined as an outer coating applied to oral pharmaceutical dosage forms that prevent drug release in the stomach but allows it in the small intestine using polymers that are insoluble at acidic pH but soluble at intestinal pH.
Applicant next contends that Dohil’s inclusion of Eudragit® RL and RS polymers as part of the enteric coating materials definition is in error, as it is asserted that neither the Eudragit® RL nor RS polymers are enteric coating materials.
The Examiner, in response, respectfully disagrees and maintains the rejection for the reasons already of record. It is respectfully acknowledged that the inclusion of the polymers at issue could be in error. However, there is nothing of record to substantiate this assertion. As it stands, Dohil discloses both Eudragit® RL and RS polymers as species defining the enteric coating of the practiced inventions.
As to the assertion that these polymers are not enteric coating materials, the Examiner also respectfully disagrees and submits that the state-of-the-art teaches that they are known for such a use. Patra et al. (FJPS; 2017) is submitted here as evidence supporting this position. Eudragit RS polymers, dosage/delivery systems, and their applications are disclosed in Table 5, while Eudragit RL polymers, dosage/delivery systems, and their applications are disclosed in Table 7.
Thus, disclosure of these polymers as enteric materials is considered to meet the amended property limitations (e.g., >4 hr Cmax) as well as the newly presented dosing limitations of claim 28. Furthermore, ¶[0065] discloses that the cystamine composition is administered at a total daily dose of from approximately 0.25 g/m2 to 4.0 g/m2 body surface area, thereby expressly meeting the newly presented limitation.
Thus, for these reasons, Applicant’s arguments are found unpersuasive. The above rejection is hereby maintained.
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
This application currently names joint inventors. In considering patentability of the claims the Examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the Examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 5-9, 11-13, 16, and 21-28 are rejected under 35 U.S.C. 103 as being unpatentable over Dohil (WO 2018/093364 A1). [emphasis added to reflect added/canceled claims]
The limitations of claims 5-9, 11, 12, 16, and 22-28 are discussed above.
The teachings of Dohil are presented above and are noted as disclosing an oral dosage form, such as an enterically-coated tablet core comprising cystamine dihydrochloride and a binder (e.g., claims 1, 3, 4, and 12). Paragraph [0039] additionally discloses that “the enteric coating material can be designed to rapidly dissolve at a specific pH (i.e., a pH between 4.5 and 6.5).” Such is considered to teach and suggest an immediate release dosage form.
The limitations of claims 21 and 13 are disclosed by ¶[0065]. Therein, the recited total daily dose of the administered composition of 1.35 g/m2 is taught (claim 21), as is a daily dose amount that is 40% of the total (about 0.54 g/m2).
Based on the teachings of the reference, the Examiner submits that a person of ordinary skill in the art would have had a reasonable expectation of success at producing the instantly claimed composition and arriving at the recited method of treatment. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, and absent a clear showing of evidence to the contrary.
Response to Arguments
Applicant’s arguments with regard to the rejection of claims 5-9, 11-13, 16, and 21-28 under 35 USC 103(a) as being unpatentable over the combined teachings of Dohil have been fully considered, but they are not persuasive.
Applicant traverses the rejection on the same grounds as discussed above, namely that Dohil is directed to pH-dependent release through the use of its disclosed enteric polymers, while the instantly claimed composition is time-release and pH-independent driven.
The Examiner, in response, again respectfully acknowledges this, but maintains the rejection for the reasons of record. Dohil discloses the instantly claimed Eudragit® blends RL and RS as species defining the practiced enteric polymer materials and with those polymers, so too are their properties disclosed. See MPEP §2112.01(I) and (II). Though not presented as an argument in response to this rejection, it is implied; the disclosure of Eudragit® blends RL and RS as defining species of the practiced enteric polymer materials is in error within the reference. The Examiner again maintains that no evidence has been provided to support this assertion.
Applicant’s arguments, for the above reasons, are found unpersuasive. Said rejection is therefore maintained.
Claims 5-16, 18, and 20-28 are rejected under 35 U.S.C. 103 as being unpatentable over Dohil (USPN 8,026,284 B2; herein “Dohil (‘284)”), further in view of Dohil (WO 2019/010024 A1; herein “Dohil (‘024)”). [emphasis added to reflect added/canceled claims]
The limitations of claims 5-9, 11-13, 16, and 21-28 are discussed above.
Dohil (‘284) discloses oral, controlled-release compositions comprising pharmaceutically acceptable salts of cystamine for the treatment of cystinosis (see e.g., Abstract; claim 1). The practiced dosage form is taught as being an enterically coated form, such as an enterically coated tablet (see e.g., col. 6, lines 5-8; col. 9, lines 1-21). Polymers disclosed by Dohil as being representative of the enteric polymers that may be used to coat said tablets include both Eudragit RL and Eudragit RS (see col. 7, lines 14-27; specifically, lines 25-27; claim 25). Tablets are disclosed as being produced by combining the drug with excipients such as binders, diluents, disintegrants, lubricants, fillers, carriers and the like (see e.g., col. 8, lines 8-14).
The practiced dosage forms are disclosed as being administered “twice per day” to “less than four times daily” (see e.g., claims 1 and 10). The total dosage of cystamine per day is disclosed as being 1.35 g/m2/day (see e.g., claim 12). The limitations of instant claim 13 additionally recite that the dosage form of claim 12 comprises in total about 40% of a daily dose of cystamine. Given the above daily dose of 1.35 g/m2/day, 40% of this dose calculates to be about 0.54 g/m2/day. Claim 2 discloses that each dose of cystamine will be about 0.5-1.0 1.35 g/m2, thereby meeting the claim.
The foregoing is considered to teach the limitations of claims 5-9, 11-13, 16, and 20-28.
The teachings of Dohil (‘284) are deficient with respect to the instant claims.
Dohil (‘024) supplements the teachings of Dohil (‘284) disclosing in ¶[0034] that “[c]ystamine is generally handled as the dihydrochloride” and that “cystamine in the body is reduced to cysteamine and RS-cysteamine mixed disulphide.” Based on this definition in the art, the Examiner broadly and reasonably interprets the salt of Dohil (‘284) as being synonymous with cystamine dihydrochloride, and in the alternative, minimally presenting a person of ordinary skill in the art with a reasonable expectation of the ‘284 reference as teaching the dihydrochloride salt.
Similarly, with respect to claims 12, 14, and 15, where it pertains to defining the unit dosage form as being a combination of immediate release and “large intestine release (LIR)” (i.e., delayed or sustained release), the Examiner again concedes that Dohil (‘284) does not disclose this particular form of biphasic release.
Dohil (‘024) remedies this deficiency disclosing that different formulations of cystamine salt are known, such as immediate release, delayed release, extended release, delayed and extended release, immediate and extended release, etc. See ¶[0047]. This is considered to teach and suggest that biphasic release of cystamine dihydrochloride would have been well within the purview of the skilled artisan.
Regarding the recited percent combinations of the total daily dose, Dohil (‘024), like the ‘284 reference, discloses that total daily dose of cystamine is about 1.35 g/m2/day and that other dose amounts encompassed by the reference include broader ranges such as from approximately 0.25 g/m2 (i.e., about 16.6% of the total daily dose) to 4.0 g/m2, and include more specific amounts such as about 0.3 g/m2 (i.e., about 23.4% of the total daily dose). See ¶[0083].
Lastly, regarding the limitations of claim 18, the Examiner notes that both references teach and suggest that the cystamine dosage forms are administered multiple times per day, with the ‘284 reference disclosing that the dosage form is taken less than four times per day. The ‘284 reference additionally discloses that the patients with cystinosis are required to ingest oral cysteamine every 6 hours and that when taken regularly, cysteamine can deplete intracellular cystine by up to 90% (as measured in circulating white blood cells) (see col. 13, lines 40-44).
The Examiner concedes that the Cystagon® dosage form is not expressly the dosage form that reads on the instantly administered composition. However, it is considered to convey to the ordinarily skilled artisan the importance of providing and maintaining constant therapeutic levels of cysteamine or cystamine to the patient in need thereof. Such is additionally considered to be taught and suggested by the disclosures of administering the doses over frequencies of 2-4 times per day as discussed above.
Based on the combined teachings of the references, the Examiner submits that a person of ordinary skill in the art would have had a reasonable expectation of success at producing the instantly claimed composition and arriving at the recited method of treatment. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, and absent a clear showing of evidence to the contrary.
Response to Arguments
Applicants’ arguments with regard to the rejection of claims 5-16, 18, and 20-28 under 35 USC 103(a) as being unpatentable over the combined teachings of Dohil (‘284) and Dohil (‘024) have been fully considered, but they are not persuasive.
Applicant traverses the rejection on the same grounds as discussed above, namely that Dohil is directed to pH-dependent release through the use of its disclosed enteric polymers, while the instantly claimed composition is time-release and pH-independent driven.
The Examiner, in response, again respectfully acknowledges this, but maintains the rejection for the reasons of record. Dohil discloses the instantly claimed Eudragit® blends RL and RS as species defining the practiced enteric polymer materials and with those polymers, so too are their properties disclosed. See MPEP §2112.01(I) and (II). Though not presented as an argument in response to this rejection, it is implied; the disclosure of Eudragit® blends RL and RS as defining species of the practiced enteric polymer materials is in error within the reference. The Examiner again maintains that no evidence has been provided to support this assertion.
Applicant’s arguments, for the above reasons, are found unpersuasive. Said rejection is therefore maintained.
All claims under consideration remain rejected; no claims are allowed.
Conclusion
THIS ACTION IS MADE FINAL. 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 extension fee 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.
Correspondence
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Jeffrey T. Palenik whose telephone number is (571) 270-1966. The Examiner can normally be reached on 9:30 am - 7:00 pm; M-F (EST).
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Robert A. Wax can be reached on (571) 272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Jeffrey T. Palenik/
Primary Examiner, Art Unit 1615