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 .
Application Status
2. Applicant's amendment and response, submitted November 25, 2025 has been reviewed by the examiner and entered of record in the file.
3. Claims 10 and 17 are amended; and claims 3 and 4 are canceled. Claims 28 and 29 are newly added. Claims 10, 11, 17-26, 28 and 29 are present in the application.
4. Claims 20-26 (Group II, drawn to methods) remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to an invention nonelected without traverse, there being no allowable generic or linking claim.
5. Claims 10, 11, 17-19, 28 and 29 are under examination and are the subject of this office action.
Information Disclosure Statement
6. The information disclosure statement (IDS) submitted on November 25, 2025, is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner, please refer to the initialed and signed copy of Applicant’s PTO-1449 form, attached herewith.
Previous Claim Rejections - 35 USC § 112(a)
7. 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.
8. Claims 10, 17 and 19, as amended, remain rejected and claim 28 is newly 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 claims contain 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, at the time the application was filed, had possession of the claimed invention. In particular, support cannot be found for the entire scope of compounds of Formula (IV) or Formula (V), as instantly claimed.
This rejection has been modified as a result of Applicant’s amendatory changes to claims 10 and 17.
9. Applicant amended independent claims 10 and 17 to limit the genus of compounds of Formula (IV) or Formula (V), in particular the definitions of R1 and R3 have been amended such that R1 and R3 are limited to C1-10aliphatic-C6-14aryl, C1-10aliphatic-pyridinyl, C6-14 aryl, and pyridinyl; and R5 is limited to hydrogen, C1-10 aliphatic, or pyridinyl; and has narrowed the definition of R2 to embrace the fluorophore moieties: 4-methyl-2H-chromen-2-one, coumarin, fluorescein, rhodamine, eosin, rhodol, or a methylrhodol fluorophore. However, the full scope of fluorophores presently embraced by R2 still lacks sufficient description in the Specification.
10. The MPEP §2163 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 by him. In the case of chemical entities, Applicant's attention is further directed to Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559 (Fed. Cir. 1997), cert. denied, 523 U.S. 1089, 118 S. Ct. 1548 (1998), which notes that an adequate written description requires a precise definition, such as by structure, formula, chemical name, or physical properties, “not a mere wish or plan for obtaining the claimed chemical invention.” While the court recognizes that, “[i]n claims involving chemical materials, generic formulae usually indicate with specificity what the generic claims encompass” (Id.), it is also recognized that for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim and/or the genus must be sufficiently detailed to show that applicant was in possession of the claimed invention as a whole (see Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555 (Fed. Cir. 1991)). If a genus has substantial variance, the disclosure must present a sufficient number of representative species that encompass the genus in order to adequately describe the genus (i.e., the disclosure must describe a sufficient variety of species to reflect the variation within that genus). See MPEP § 2163. Otherwise, as stated by the court in Ariad Pharmaceuticals, Inc., v. Eli Lilly and Company (Fed. Cir. 2010), “a generic claim may define the boundaries of a vast genus of chemical compounds, and yet the question may still remain whether the specification, including original claim language, demonstrates that the Applicant has invented species sufficient to support a claim to a genus.
11. In the instant case, it is evident that the genus of compounds embraced by Formula (IV) or Formula (V) has substantial breadth and variance regarding the fluorophore moiety, i.e., the genus of Formula (IV) or Formula (V) embraces hundreds of thousands of potential compounds bearing no structural resemblance to one another what-so-ever, i.e., those containing a fluorophore moiety selected from methylrhodol, 2-(2-methoxyethyl)-1H-benzo[delisoquinoline-1,3(2H)-dione, 4- methyl-2H-chromen-2-one, coumarin, hydroxycoumarin, aminocoumarin, methoxycoumarin, naphthalimide, fluorescein, rhodamine, eosin, rhodol, Cy3, Cy5, indocarbocyanine, oxacarbocyanine, thiacarbocyanine, or merocyanine.
12. Yet, the instant Specification discloses only about a dozen compound species embraced by either Formula (IV) or (V), as recited, comprising only one fluorophore moiety, i.e., the moiety recited for R2 in claims 11, 18, and 29 (see pages 16-17).
13. While the MPEP does not define what constitutes a sufficient number of representative species, the courts have indicated what does not constitute a representative number of species to adequately describe a broad generic. For example, in In re Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872 F.2d 1008 (Fed. Cir. 1989). In the instant case, it is similarly determined that the disclosure of a few dozen structurally unrelated compound species according to different Formulae (IV) and (V) does not adequately describe a subgenus embracing hundreds of millions of additional compound species bearing no structural relationship with those few dozen disclosed compounds. That is, the Specification does not disclose a sufficient variety of species to reflect the extreme variance in the recited genus of claim 1.
14. 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.
As such, claims 10, 17, 19 and 28 are rejected.
Response to Arguments
15. Applicant traverses the previous rejection under written description, and argues the following points:
(i) Applicant has amended independent claims 10 and 17 to limit the scope of the genus of compounds of Formula (IV) and Formula (V), specifically, R1 and R3 have been amended such that R1 and R3 are limited to C1-10aliphatic-C6-14aryl, C1-10aliphatic-pyridinyl, C6-14 aryl, and pyridinyl; and R5 is limited to hydrogen, C1-10 aliphatic, or pyridinyl; and R2 is limited to the fluorophore moieties: 4-methyl-2H-chromen-2-one, coumarin, fluorescein, rhodamine, eosin, rhodol, or a methylrhodol fluorophore. Regarding the scope of fluorophore groups presently recited by claims 10 and 17, Applicant argues that the disclosure provides more than adequate written description support showing that the inventors were in possession of compounds comprising all fluorophore groups recited by claims 10 and 17, i.e., wherein R2 is "a 4-methyl-2H-chromen-2-one fluorophore, a coumarin fluorophore, a fluorescein fluorophore, a rhodamine fluorophore, an eosin fluorophore, a rhodol fluorophore, or a methylrhodol fluorophore."
Applicant argues that the instant specification provides an explicit definition of "fluorophore," which recites xanthene fluorophores as options and further identifies fluorescein, rhodamine, and eosin fluorophores as falling within this class of fluorophores. Specification, page 7. Applicant contends that the fluorophore definition also indicates that methylrhodol and rhodol fluorophores fall in a structural class of fluorophores that also includes rhodamine - the fluorone class of flurophores. Applicant argues that the specification specifically identifies fluorescein, rhodamine, rhodol, and methylrhodol fluorophores as exemplary fluorophores suitable for use as the R2 group (e.g., see page 13), and describes these particular fluorophores as being within similar generic classes (xanthene and fluorone fluorophores) and expressly identifies them by name. Applicant alleges that the specification's express inclusion of "rhodamine," "eosin," "rhodol," and methylrhodol as fluorophores directly evidences Applicant's possession of those embodiments.
(ii) Applicant argues that the specification also provides multiple reaction schemes - e.g., Schemes 1, 2A, and 2B, which describe how fluorophore-containing R2 groups, are incorporated into compounds according to Formulas IV and V. Applicant alleges that a person skilled in the art would readily understand that rhodamine, eosin, methylrhodol, and rhodol fluorophores, which possess the same or similar functional "coupling handles" as fluorescein (i.e., amines and hydroxyl groups), can be substituted in the disclosed schemes without modification of the synthesis, for example, amine and hydroxyl groups on aryl groups were recognized as bioisosteres at the time of Applicant's effective filing date (see Exhibit A, page 3150, Section 2) and thus successful incorporation of a fluorophore comprising an amine group at one (or both) of the positions that bear the hydroxyl groups in the fluorescein skeleton would have been expected. Applicant alleges that the specification not only provides definitions and general guidance of compounds comprising such fluorophore groups, but it also provides operative examples and generic synthesis information sufficient to demonstrate possession of additional species of fluorophores (e.g., rhodamine, eosin, methylrhodol, and rhodol fluorophores), particularly since such fluorophores are structurally similar to fluorescein (which is expressly described in the specification) and they comprise amine groups that would be expected to react the same as the hydroxyl groups of fluorescein to arrive at compounds comprising such fluorophores.
Applicant provides Exhibits B and C “as additional evidence of the above-stated position,” which confirm that rhodamine fluorophores are routinely coupled with other chemical entities using the same functional groups and reaction conditions described in Applicant's specification. Exhibits B and C were published in 2008 and 2011, respectively, and are articles from peer-reviewed scientific journals. Scheme 1 of Exhibit B demonstrates synthesis of a rhodamine fluorophore-containing compound using the same type of chemistry used in Applicant's disclosure for coupling fluorescein as shown in Scheme 2B. In Exhibit C, Figure 2 illustrates that a rhodamine fluorophore is coupled at the amine-bearing position using an acid chloride-containing coupling partner and conditions similar to that described by Applicant's specification in Schemes 1 and 2. Applicant argues that Exhibits B and C therefore serve as additional evidence that a POSITA would have understood the inventors to be in possession of compounds comprising rhodamine, eosin, rhodol, and methylrhodol fluorophores.
Applicant contends that the written description requirement must be applied in light of what POSITA would have understood at the time of filing, and as articulated in M.P.E.P. § 2163 and the cases cited therein, "what is conventional or well known to one of ordinary skill in the art need not be disclosed in detail" (citing Hybritech Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1384, (Fed. Cir. 1986)). Applicant alleges that under Vas-Cath and Martin v. Johnson, an inventor need not set forth "every nuance" or use "the same words" (ipsis verbis) to demonstrate possession of the invention, i.e., coupling rhodamine, rhodol, methylrhodol, and/or eosin fluorophores to another chemical moiety via their amine and/or hydroxyl handles was known in the art prior to Applicant's invention (taught in Exhibits B and C). And, hydroxyl and amine groups are "classical bioisosteres," as discussed above. Considering these facts in combination with the fact that Applicant's specification illustrates how to couple fluorescein (which comprises phenol handles) to its disulfide scaffold and the fact that Applicant's specification describes other fluorophores falling within the genus to which fluorescein belongs, no additional details need be provided to establish compliance with the written description requirement. A POSITA reading the specification's explicit listing of "rhodamine," "methylrhodol," "eosin," and "rhodol" as fluorophores, together with the provided synthetic schemes that are clearly applicable to these fluorophores, would have fully understood that Applicant possessed the recited rhodamine-, methylrhodol-, eosin-, and rhodol- containing compound embodiments at the time of filing. Therefore, the written description requirement is satisfied.
Applicant contends that a similar argument applies to the recited "coumarin fluorophore." Applicant submits Exhibit D, a journal article published by Dr. Mike Pluth, an inventor of the present invention, which was published in 2024, and teaches that coumarin fluorophores were incorporated into structures according to Formulas IV and V, as described Applicant's specification. Applicant argues that FIG. 2 of Exhibit D proves that coumarin fluorophores can be attached to disulfide-containing groups like those illustrated in Schemes 1, 2A, and 2B using the same conditions described in these schemes, and as confirmed by Exhibit D, the coumarin fluorophore is attached to the disulfide-containing moiety via a hydroxyl group, just like the fluorescein fluorophore illustrated in Schemes 2A and 2B. Applicant argues that the specification expressly lists a coumarin fluorophore as an exemplary R2 group and further describes coumarin fluorophores with different functional groups that can be used to attach the coumarin fluorophore (e.g., a hydroxyl functional group, like with hydroxycoumarin and which can be obtained from methoxycoumarin, both disclosed by Applicant's specification; and an amine, like with aminocoumarin, which also is disclosed by Applicant's specification). Applicant contends that a POSITA would have recognized that the inventors were in possession of compounds comprising a coumarin fluorophore as an R2 group.
16. Applicant's arguments have been fully considered but they are not persuasive. While Applicant’s amendment to the claims limits the groups embraced by the R1, R3 and R5 moieties, the scope of fluorophore compounds embraced by R2 still has substantial variance and is not supported by the instant Specification. The genus of compounds embraced by Formula (IV) or Formula (V) comprising a fluorophore moiety selected from 4- methyl-2H-chromen-2-one, coumarin, fluorescein, rhodamine, eosin, rhodol, and methylrhodol.
As stated previously, the instant Specification discloses only a dozen compound species embraced by either Formula (IV) or (V), as amended, which contain only one of the recited fluorophores, fluorescein:
PNG
media_image1.png
89
116
media_image1.png
Greyscale
(see pages 16-17).
17. As such, the Specification is lacking sufficient written description to identify the genus of the claim and/or sufficient detail to show that Applicant was in possession of the claimed invention as a whole (see Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555 (Fed. Cir. 1991)). If a genus has substantial variance, as in this case, the disclosure must present a sufficient number of representative species that encompass the genus in order to adequately describe the genus (i.e., the disclosure must describe a sufficient variety of species to reflect the variation within that genus). See MPEP § 2163.
Applicant alleges that under Vas-Cath and Martin v. Johnson, an inventor need not set forth "every nuance" or use "the same words" (ipsis verbis) to demonstrate possession of the invention, such that coupling rhodamine, rhodol, methylrhodol, and/or eosin fluorophores to another chemical moiety via their amine and/or hydroxyl handles was known in the art prior to the claimed invention. Applicant alleges that said coupling is confirmed by both Exhibits B and C. Even if the examiner agreed with Applicant’s allegation that one skilled in the art reading the specification's explicit listing of "rhodamine," "methylrhodol," "eosin," and "rhodol" fluorophores, together with the provided synthetic schemes, and the teachings of Exhibits B, C, and D, would have fully understood that Applicant possessed the full scope of recited fluorophore containing compounds at the time of filing, it is noted that Exhibits B and C are directed to the synthesis of rhodamine fluorophore-containing compounds only. While the examiner acknowledges that the fluorophores fluorescein, rhodamine, rhodol, and methyl-rhodol are structurally similar, it is noted that the other fluorophores, coumarin, eosin, and 4-methyl-2H-chromen-2-one, are not structurally similar to these, and would not be expected to behave similarly. Applicant further relies on Exhibit D for a teaching of coumarin fluorophore-containing compounds, yet Exhibit D is published well after the effective filing date of the claimed invention.
Therefore the written description rejection of claims, 10, 17, 19 and new claim 28 is maintained. It is suggested to narrow the scope of the claims such that they are commensurate in scope with the disclosure.
Previous Claim Rejections - 35 USC § 112(b)
18. Claim 3 was previously 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.
19. Claim 3 was previously rejected as lacking sufficient antecedent basis for the limitation of “heteroaryl” in the claim, because in claim 10, the definition of R2 fails to recite a “heteroaryl” moiety.
20. In view of the amendment canceling claim 3, the previous indefiniteness rejection is withdrawn.
Previous Claim Rejections - 35 USC § 112(d)
21. Claims 3 and 4 were previously 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.
22. In view of the amendment canceling claims 3 and 4, the previous rejection under 35 U.S.C. 112(d) is withdrawn.
Claim Objections
23. Claims 11, 18 and 29 are objected to as being dependent upon an independent claim that is rejected.
Conclusion
24. Claims 10, 11, 17-26, 28 and 29 are present in the application. Claims 20-26 remain withdrawn from consideration as directed to a non-elected invention. Claims 10, 17 and 19 are rejected. Claims 11, 18 and 29 are objected to. No claim is presently allowed.
25. 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 nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
26. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JANET L COPPINS whose telephone number is (571)272-0680. The examiner can normally be reached Monday-Friday 8:30AM-5PM EST.
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, Amy Clark can be reached on 571-272-13101310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JANET L COPPINS/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628