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 .
Benefit of Earlier Filing Date
The instant application, filed 26 June 2024, is a national stage application of PCT/US2022/054144, filed 28 December 2022, which claims the benefit of an earlier filing date to U.S. Provisional Patent Application Serial No. 63/294,335, filed 28 December 2021. Acknowledgment is made of Applicant’s claim.
Restriction/Election
Requirement for Restriction/Election was mailed 01 July 2026.
Applicant’s Response to Requirement for Restriction/Election was received 01 September 2026. Because Applicant did not distinctly and specifically point out any supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
Applicant’s election of Group I (Claims 1-2, 6-24, and 28) and, “…the species of Formula I, wherein at least one of Y1-Y4 is D; R2 is
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; at least one of Y5-Y8 is D, and R1 is H,” indicating claims 1-2, 6-11, and 28 read on the elected species, in the Response filed 01 September 2026 is acknowledged.
The claims in Groups II and III and the claims drawn to a non-elected species (i.e., Claims 12-27, 33, 36, and 43-47) are withdrawn.
In accordance with MPEP § 803.02, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species, the search of the Markush-type claim will be extended. If prior art is then found that anticipates or renders obvious the non-elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be reexamined. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during reexamination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
As per MPEP § 803.02, the Examiner will determine whether the entire scope of the claims is patentable
Status of the Claims
The listing of claims filed 01 September 2026 has been examined.
Claims 1-2, 6-28, 33, 36, and 43-47 pending.
Claim 1 is amended.
Claims 12-27, 33, 36, and 43-47 are withdrawn from further consideration pursuant to 37 CFR § 1.142(b), as being drawn to a non-elected invention and species.
Claims 3-5, 29-32, 34-35, and 37-42 cancelled.
Claims 1-2, 6-11, and 28 are examined on the merits.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) filed on 07 June 2026, 13 July 2024, and 26 June 2024 are acknowledged and have been considered. Any lined-through references have not been considered and must be submitted or resubmitted in proper format for consideration.
Drawings
The drawings (i.e., Figs. 12A and 14-16) are objected to because on some drawings the axis labels, particularly the axis labels on the bar graphs in Fig. 12A and the axis labels in Figs. 14-16, are either partially or wholly unreadable. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112(a)
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.
Claim 8 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The courts have stated that, “To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated that, “A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials.” Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) (“In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus …”) Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed genus is sufficient. See MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
Claim 8 recites, “The compound of claim 1… or a pharmaceutically acceptable salt, solvate, or prodrug thereof.” Particularly, the term “prodrug” invokes the 35 U.S.C. 112(a) rejection. Even a cursory calculation of the number of compounds embraced in the instant claims would result in thousands of compounds.
Level of Skill & Knowledge in the Art
The level of skill and knowledge in the art is high.
Physical and/or Chemical Properties/Functional Characteristics
The Specification states, “The term ‘prodrug’ refers to a compound as disclosed herein that is readily convertible into the parent compound in vivo… A prodrug may be converted into the parent drug by various mechanisms, including enzymatic processes and metabolic hydrolysis.” (p. 23, ¶ [0047]). Although the art recognizes generally accepted definitions, the Specification lacks a structural prodrug description which would demonstrate that the inventor had possession of prodrugs of the compound recited by claim 8.
A review of the prior art identifies Najjar (Anas Najjar & Rafik Karaman (2019) Successes, failures, and future prospects of prodrugs and their clinical impact, Expert Opinion on Drug Discovery, 14:3, 199-220), which discloses successes and failures of prodrugs of known pharmaceuticals (p. 212, 3. Previous failed prodrugs). Najjar teaches hetacillin, an ester prodrug of ampicillin, which was withdrawn since it did not have a superior advantage when compared to ampicillin. In light of Najjar, it is unknown which of the prodrugs of the compound recited by Applicant in claim 8 will be active or inactive. Further, one of ordinary skill in the art would not be able to predict which compounds, of the vast number that are claimed, will be active or inactive absent evidence. There is no structure/function correlation in the Specification showing which prodrugs of the compound recited by claim 8 would or would not be active.
Since Applicant has not set forth compounds or substituents on Formula I in the Specification, it is not clear which other compounds are encompassed by claim 8. There is no structure/function correlation and no representative number of specific examples of prodrugs of the compound recited by claim 8 to demonstrate which prodrug compounds retain activity. Further, one of ordinary skill in the art would not be able to predict the biological activity of the claimed prodrugs of the compound recited by claim 8.
Predictability of the Art
Medicinal chemistry is an experimental science with a low predictability level. Small changes in the structure of a compound can lead to large differences in their pharmacological activity. Regarding prodrugs, predicting if a certain claimed compound retains the activity and function of the original drug is filled with experimental uncertainty because prodrugs contain variation by chemical and physical properties of the molecules.
Method of Making the Claimed Invention
While the claimed invention is directed towards cysteamine prodrugs (p. 1, ¶ [0002]), claim 8, as written, embraces prodrugs of the recited compound. Although the Specification provides methods for making a compound having the structure of Formula I (p. 75, ¶ [00175]), no method for making all of the compounds, including prodrugs of the compound recited by claim 8, has been disclosed. Methods of synthesizing compounds are, in general, known to a person of ordinary skill; however, methods of making the myriad of compounds encompassed by the instant claims is beyond the skill of the artisan, particularly when certain elements, such as prodrugs of the compound recited by claim 8, are merely described partially.
As such, the instant Specification and instant claim 8 do not provide sufficient description such that one could anticipate what additional elements may be present in the prodrugs of the compound recited by claim 8 because the examples illustrated in the experimental section are limited to only compounds of Formula I.
Written Description Conclusion
Substantial and undue experimentation would be needed to practice Applicant’s invention because the Specification lacks sufficient detail to show how to use the prodrugs of the compound recited by claim 8. Further, there is no guarantee that all of the prodrugs embraced by the scope of instant claim 8 would be useful in treating cysteamine sensitive disorders.
Even without the undue burden of experimentation, there is no guarantee that one would obtain the product of a desired prodrug of the compound recited by claim 8. Although some functional characteristics are disclosed or would be known to a person of ordinary skill in the art, in the absence of a disclosed structure, there can be no correlation between the function and structure of the claimed prodrugs of the compound recited by claim 8.
The MPEP states that written description for a genus can be achieved by a representative number of species within a broad genus. It is unquestionable that the claim(s) are broad and generic with respect to all possible compounds encompassed by the claims. In other words, the possible structural variations are limitless to any prodrugs of the genus. In the instant case, however, the Specification does not disclose a sufficient variety of species to reflect this variance in the genus. The Specification does not provide sufficient descriptive support for the myriad of compounds embraced by the claims, specifically prodrugs of the compound recited by claim 8.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”) Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention. This rejection would be overcome by amending claim 8 to remove the term “prodrug”.
Claim Rejections - 35 USC § 112(d)
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.
Claim 8 is 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.
Claim 8, which depends on claim 1, recites, “…or a pharmaceutically acceptable salt, solvate, or prodrug thereof.” [Emphasis added.] Claim 1 lacks any mention of a prodrug. Accordingly, claim 8 improperly broadens the scope of claim 1 to include prodrugs of the compound recited by claim 8.
Applicant may cancel claim 8, amend the claim to place it in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that claim 8 complies with the statutory requirements.
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 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 1-2 and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Stanton (WO 2019/060634 A1; IDS dated 26 June 2024, Cite No. 1) in view of Kushner (Kushner et al., (1999), Canadian Journal of Physiology and Pharmacology, 77(2), p. 79-88).
Regarding claims 1-2 and 28, Stanton teaches compounds for treating cysteamine sensitive symptoms, syndromes, and diseases (p. 1, Lines 4-5). One such compound is CAS Registry Number: 83851-17-6 (Drawings, p. 18/43, Fig. 18, Disulfide Table 1A, Row “1 + 16”; Drawings, p. 17/43, Fig. 17, Row #1 and #16; p. 23, Lines 21-23), shown below.
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In CAS Registry Number: 83851-17-6, R1 is an acetyl group, R2 is
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, R3 is C2alkyl, and Y1-Y4 are H.
Stanton teaches compositions comprising one or more pharmaceutically acceptable excipients, including binders, diluents, and carriers (p. 17, Lines 21-40).
Stanton does not explicitly teach a deuterated compound having the structure of Formula I.
Kushner discusses deuterium isotope effects (DIE), stating, “The C-D bond is about 10 times as strong as the C-H bond and more resistant to chemical or enzyme cleavage. Compounds with C-D bonds tend to remain stable in H2O indefinitely, and such compounds have been widely used for isotopic studies” (p. 80, Col. 2). Furthermore, with respect to the “ratio of the rates of cleavage of a C-protonated and -deuterated compound… tenfold differences in rates are common” (p. 80, Col. 2, Bottom Paragraph). Kushner states, “The existence of a DIE in comparing protonated and deuterated compounds has been widely used to show whether metabolic reactions involve cleavage of C-H bonds” (p. 80, Col. 2, Bottom Paragraph).
Additionally, Kushner writes, “…the C-D bond is more stable than the C-H bond, and such D in organic compounds is not readily exchangeable in H2O. Deuterated organic compounds can be detected with great sensitivity by mass spectrometry and other methods. Because of these considerations, and the very low toxicity of deuterated compounds (especially compared with radioactive ones) such drugs, as well as D2O are very widely used in studies of metabolism and movement of drugs and toxic substances in humans and other animals” (p. 83, Col. 1, Paragraph 3).
Kushner goes on to cite various examples of deuterium-enriched drugs, synthesized to study their metabolic activities. For instance, “Drugs of special interest are those whose deuterated forms have different pharmacological effects than the fully hydrogenated forms… Sometimes changed properties are due to different transport penetration of the drug itself… More often, changes in pharmacological action seem due to changes in drug metabolism… One of the key steps in all such reactions is the breaking of a C-H bond, and compounds that have C-D structures at the site of enzymatic attack are more resistant to P450 change” (p. 83, Col. 2, Paragraph 2). Furthermore, “Resistance to P450-induced changes may lead to an increase in duration of pharmacological action… Sometimes, however, oxidation leads not to the destruction of a drug but to the formation of the active compound. In such a case, deuteration can reduce the drug’s activity… Deuteration can also cause “metabolic switching,” whereby the paths of metabolism of a drug are quantitatively changed” (p. 83, Col. 2, Paragraphs 2-5).
Kushner states, “The metabolic products of many drugs are toxic, and deuteration can lower such toxicity by reducing metabolism… Van Langenhove (1986) pointed out that the ability of deuterium labeling to change drug metabolism must be kept in mind in using such drugs in pharmacokinetic studies and studies of drug and enzyme metabolism” (p. 84, Col. 2, Paragraphs 1-2). In addition, “Certain deuterated antimicrobial compounds are less susceptible to breakdown by their target microorganisms and hence are more effective” (p. 84, Col. 2, Paragraph 5).
Finally, Kushner concludes, “Action of deuterated drugs, a less complex subject, has been more easily understood, although with few practical therapeutic consequences” (p. 85, Col. 1, Paragraph 4). Kushner quotes other reviewers, saying, “At present time there are no drugs on the market that contain deuterium in the molecule” (p. 85, Col. 1, Paragraph 5). However, “Their use in studies of drug metabolism is very well established, as is their contribution to studies of other biochemical pathways. D was one of the very first isotopes to be used in such studies and it is a key element in many biochemical and structural studies… The continuing need for this compound and for deuterated compounds in general, in physiological, pharmacological, and biochemical studies, cannot be questioned” (Citations Omitted; p. 85, Col. 2, Paragraph 3).
Kushner does not explicitly teach a compound having the structure of Formula I.
Prior to the filing of the instant application, a person having ordinary skill in the art (PHOSITA) following the teachings of Stanton would have found it prima facie obvious to synthesize a deuterated analog of a compound having the structure of Formula I based on the teachings of Kushner. The examiner provided an extensive recitation of Kushner in order to establish the prevalence of deuterium-enriched drugs in the art. Furthermore, as suggested by Kushner, deuteration can confer advantageous properties such as lessening toxicity by reducing metabolism. Accordingly, a PHOSITA would have been motivated to try deuterating compounds disclosed by Stanton while searching for other compounds useful in treating cysteamine sensitive disorders. Additionally, Stanton discloses compositions comprising various pharmaceutically acceptable excipients, so a PHOSITA would have been motivated to include the aforementioned deuterated compounds in a pharmaceutical composition.
Allowable Subject Matter
Claims 6-7 and 9-11 contain allowable subject matter. None of the prior art of record nor a search in the pertinent art area teaches a compound having a structural formula of Formula II(a) (Claim 6), shown below.
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The following is a statement of reasons for the indicated of allowable subject matter:
The closest prior art is Stanton (WO 2019/060634 A1; IDS dated 26 June 2024, Cite No. 1). Shown below is a compound disclosed by Stanton (Drawings, p. 18/43, Fig. 18, Disulfide Table 1A, Row “1 + 16”; Drawings, p. 17/43, Fig. 17, Row #1 and #16; p. 23, Lines 21-23), which shares some structural similarities to the instantly claimed compounds:
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The instantly claimed compounds differ from Stanton in the following respects:
In the instantly claimed compounds, the group corresponding to R2 in Formula I is
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. However, in the compound disclosed by Stanton, the S atom is instead O and the structure is missing the additional NH2 substitution in R2.
Thus, while Stanton’s compound shares some structural similarities with the instantly claimed compounds having a structure of Formula II(a), a skilled artisan would not have been motivated to make the aforementioned changes as a whole to the structures which would have predictably resulted in compounds having a structure of Formula II(a).
Conclusion
Claims 1-2, 8, and 28 are rejected.
Claims 6-7 and 9-11 are objected to as being dependent upon a rejected base claim.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIANNA L BAUER whose telephone number is (571)272-5752. The examiner can normally be reached 8am-5pm.
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, ADAM C MILLIGAN can be reached at (571)270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/B.L.B./Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
