DETAILED ACTION
Notice of Pre-AIA or AIA Status
The inventor or joint inventor should note that the instant invention, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1-14, 17, 20 and 21 are pending in the instant invention. According to the Amendments to the Claims, filed August 20, 2026, claims 1-14 and 17 were amended and claims 15, 16, 18 and 19 were cancelled.
Status of Priority Objection - Priority Date
This invention was filed on December 20, 2023.
Similarly, the inventor or joint inventor should further note that this invention’s claim to priority under 35 U.S.C. § 119(e) to US Provisional Application No. 63/476,193, filed December 20, 2022, was objected to in the Non-Final Rejection, mailed on May 20, 2026. Consequently, the effective filing date, for examination and prosecution on the merits, is that of the instant invention, filed December 20, 2023.
Status of Restrictions / Election of Species
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The inventor’s or joint inventor’s affirmation of the following election, with traverse, in the reply filed on August 20, 2026, is acknowledged: a) Group I - claims 1-14 and 17; and b) substituted rhodamine - p. 15.
Similarly, the inventor or joint inventor should further note that the requirement was made FINAL in the Non-Final Rejection, mailed on May 20, 2026.
Likewise, the inventor or joint inventor should further note that this invention contains claims 20 and 21, drawn to nonelected inventions, with traverse, in the reply filed on August 20, 2026. A complete reply to the Final Rejection must include cancellation of nonelected claims or other appropriate action (37 CFR 1.144). See MPEP § 821.01.
Next, the inventor or joint inventor should further note that the sections of U.S.C. Title 35 that formed the basis of prior rejections formulated, as well as any references supporting said rejections, that are not included with this Office action, may be found in the Non-Final Rejection, mailed on May 20, 2026.
Moreover, the inventor or joint inventor should further note that any rejections and/or objections of record not explicitly addressed herein below, are hereby withdrawn, in light of the inventor’s or joint inventor’s arguments and/or the Amendments to the Claims, filed August 20, 2026.
Thus, a second Office action and prosecution on the merits of claims 1-14 and 17 is contained within.
Status of Claim Rejections - 35 U.S.C. § 112(a)
The inventor’s or joint inventor’s arguments, on pages 14-19 of the Remarks, filed August 20, 2026, with respect to claims 18 and 19, have been fully considered, but will not be discussed further, since, according to the Amendments to the Claims, filed August 20, 2026, claims 18 and 19 have been cancelled by the inventor or joint inventor.
The inventor’s or joint inventor’s arguments, on pages 14-19 of the Remarks, filed August 20, 2026, with respect to claims 1, 2, 4-7, 9 and 14-17, have been fully considered, but are not persuasive. Consequently, the rejection of claims 1, 2, 4-7, 9 and 14-17, made in the Non-Final Rejection, mailed on May 20, 2026, is hereby maintained for the reasons of record.
The inventor or joint inventor primarily argues that the specification teaches a person of ordinary skill in the art how to make and use the full scope of the claimed invention, without undue experimentation. Similarly, the inventor or joint inventor further argues that the instantly recited substituted rhodamines are fully enabled.
In response to the inventor’s or joint inventor’s argument that (1) the specification teaches a person of ordinary skill in the art how to make and use the full scope of the claimed invention, without undue experimentation, and that (2) the instantly recited substituted rhodamines are fully enabled, the Examiner respectfully disagrees, since [T]he specification must teach how to make and use the invention, not teach how to figure out for oneself how to make and use the invention. {See In re Gardner, 166 USPQ 138 (CCPA 1970)}.
Likewise, the inventor’s or joint inventor’s elected invention is directed to Group I, drawn to substituted rhodamines. Based on the guidance provided by the specification and, absent any evidence to the contrary, it is presently unclear whether a substituted rhodamine, where R1 and SLP are not as presented herein in the section below entitled New Claim Objections, is either synthetically feasible or possesses utility as a fluorophore.
The Examiner requires that the inventor or joint inventor: a) discretely indicate where the specification enables one of ordinary skill in the art to make the substituted rhodamines, where R1 and SLP are not as presented herein in the section below entitled New Claim Objections; and b) discretely identify enabling disclosure that will allow one of ordinary skill in the art to use the substituted rhodamines, where R1 and SLP are not as presented herein in the section below entitled New Claim Objections, as a fluorophore, to overcome this rejection.
The inventor or joint inventor should note that (a) [I]t is not the function of claims to specify impossible or inoperative species {See In re Anderson, 176 USPQ 33I (CCPA 1973); and In re Angstadt, 190 USPQ 214, 219 (CCPA 1976)}, and that (b) [A] rejection under 35 U.S.C. § 112(a) is proper if the claims contain a significant number of seemingly inoperative embodiments. {See In re Corkill, 771 F.2d 1496, 226 USPQ 1005 (Fed. Cir. 1985); In re Langer, 503 F. 2d 1380, 183 USPQ 288 (CCPA 1974); and Schering Corp. v. Gilbert, 153 F.2d 428, 68 USPQ 84 (2d Cir. 1946), mod’g, Schering Corp. v. Gilbert, 67 USPQ 42 (SDNY 1945)}.
Next, the inventor or joint inventor should further note that the enablement requirement refers to the requirement of 35 U.S.C. § 112(a) that the specification describe how to make and how to use the invention. The invention that one skilled in the art must be enabled to make and use is that defined by the claims of the particular invention or patent.
Then, the inventor or joint inventor should further note that the purpose of the requirement that the specification describe the invention in such terms that one skilled in the art can make and use the claimed invention is to ensure that the invention is communicated to the interested public in a meaningful way. The information contained in the disclosure of an invention must be sufficient to inform those skilled in the relevant art how to both make and use the claimed invention. A patent claim is invalid if it is not supported by an enabling disclosure.
Consequently, the inventor or joint inventor should further note that [T]he enablement requirement ensures that the public knowledge is enriched by the patent specification to a degree at least commensurate with the scope of the claims. {See National Recovery Technologies Inc. v. Magnetic Separation Systems Inc., 49 USPQ2d 1671 (Fed. Cir. 1999); and Sitrick v. Dreamworks LLC, 85 USPQ2d 1826 (Fed. Cir. 2008)}.
Moreover, the inventor or joint inventor should further note that any analysis of whether a particular claim is supported by the disclosure in an invention requires a determination of whether that disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention. The standard for determining whether the specification meets the enablement requirement was cast in the Supreme Court decision which postured the question: [I]s the experimentation needed to practice the invention undue or unreasonable? {See Minerals
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Separation
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, Ltd.,
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, 242 U.S. 261, 271 (1916). That standard is still the one to be applied. {See In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)}.
Accordingly, the inventor or joint inventor should further note that [T]he specification must provide sufficient teaching such that one skilled in the art could make and use the full scope of the invention, without undue experimentation. {See In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988); United States v. Telectronics, Inc., 857 F.2d 778, 785, 8 USPQ2d 1217, 1223 (Fed. Cir. 1988); and CFMT Inc. v. Yieldup International Corp., 68 USPQ2d 1940 (Fed. Cir. 2003)}.
Furthermore, the inventor or joint inventor should also note that [O]nce the Examiner has weighed all the evidence and establishes a prima facie case of lack of enablement for the claimed invention, the burden falls on the inventor or joint inventor to present persuasive arguments, supported by suitable proofs where necessary, that one skilled in the art would be able to make and/or use the claimed invention using the invention as a guide. {See In re Brandstadter, 484 F.2d 1395, 1406-07, 179 USPQ 286, 294 (CCPA 1973)}.
Also, the inventor or joint inventor should further note that [T]o establish enablement for the claimed invention, the inventor or joint inventor may submit factual affidavits or declarations under 37 CFR § 1.132 or cite references to show what one skilled in the art knew at the time of filing the invention. {See In re Buchner, 929 F.2d 660, 661, 18 USPQ2d 1331, 1332 (Fed. Cir. 1991); and MPEP § 2164.05}.
As a result of the Amendments to the Claims, filed August 20, 2026, and to clarify the record, the original rejection, made in the Non-Final Rejection, mailed on May 20, 2026, is amended below, in the section entitled New Claim Rejections - 35 U.S.C. § 112(a), to omit cancelled claims 18 and 19.
Status of Claim Rejections - 35 U.S.C. § 112(b)
The inventor’s or joint inventor’s arguments, on pages 19-21 of the Remarks, filed August 20, 2026, with respect to claims 18 and 19, have been fully considered, but will not be discussed further, since according to the Amendments to the Claims, filed August 20, 2026, claims 18 and 19 have been cancelled by the inventor or joint inventor.
The inventor’s or joint inventor’s arguments, on pages 19-21 of the Remarks, filed August 20, 2026, with respect to claims 1, 2, 4-7, 9 and 14-17, have been fully considered, but are not persuasive. Consequently, the rejections of claims 1, 2, 4-7, 9 and 14-17, made in the Non-Final Rejection, mailed on May 20, 2026, are hereby maintained for the reasons of record.
The inventor or joint inventor primarily argues that the terms and/or phrases, self-labeling protein (SLP) ligand, affinity tag-containing moiety, and protein-manipulation moiety, respectively, are not terms of degree. Similarly, the inventor or joint inventor further argues that one of ordinary skill in the art viewing the specification would understand that the terms and/or phrases, self-labeling protein (SLP) ligand, affinity tag-containing moiety, and protein-manipulation moiety, respectively, are definite.
In response to the inventor’s or joint inventor’s argument that (1) the terms and/or phrases, self-labeling protein (SLP) ligand, affinity tag-containing moiety, and protein-manipulation moiety, respectively, are not terms of degree, and that (2) one of ordinary skill in the art viewing the specification would understand that the terms and/or phrases, self-labeling protein (SLP) ligand, affinity tag-containing moiety, and protein-manipulation moiety, respectively, are definite, the Examiner respectfully disagrees, since 35 U.S.C. § 112(b) requires that the claims particularly point out the subject matter that the inventor or joint inventor regards as the invention.
Likewise, the inventor or joint inventor should further note that [A] claim referring to the specification is improper. {See Ex parte Fressola, 27 USPQ 2d 1608 (BPAI 1993)}.
Next, the inventor or joint inventor should further note that [W]hen the scope of the claims can’t be determined when considered in light of the specification, a rejection under 35 U.S.C. § 112(b) is proper. {See In re Wiggins, 488 F.2d 538, 179 USPQ 421 (CCPA 1973)}.
Then, the inventor or joint inventor should further note that [A]s the statutory language of particular[ity] and distinct[ness] indicates, claims are required to be cast in clear terms, as opposed to ambiguous, vague or indefinite terms. It is the claims that notify the public of what is within the protections of the patent and what is not. {See Merrill v. Yeomans, 94 US 568, 573-74 (1876); United Carbon Co. v. Binney & Smith Co., 317 US 228, 236, 55 USPQ 381 (1942)}.
Moreover, the inventor or joint inventor should further note that [T]he USPTO may properly reject a patent invention claim as indefinite for failure to meet statutory requirements of 35 U.S.C. § 112(b) if the PTO identifies ways in which claim language is ambiguous, vague, incoherent, opaque or otherwise unclear in describing and defining the claimed invention, and if the inventor or joint inventor thereafter fails to provide satisfactory response by, for example, modifying language, providing separate definition of unclear language, or, if appropriate, persuasive explanation as to why language is not unclear, since this prima facie case determination is grounded both in the PTO’s responsibility to examine a claim to ensure that it particularly points out and distinctly claims subject matter and in examination’s attendant interactive process. {See In re Packard, 110 USPQ2d 1785 (Fed. Cir. 2014)}.
Furthermore, the inventor or joint inventor should also note that [R]ather than requiring that the claims are insolubly ambiguous, we hold that if a claim is amenable to two or more plausible claim constructions, the USPTO is justified in requiring the inventor or joint inventor to more precisely define the metes and bounds of the claimed invention by holding the claim unpatentable under 35 U.S.C. § 112(b) as indefinite. {See Ex Parte Miyazaki, 89 USPQ2d 1207, 1211 (BPAI 2008)}.
Also, the inventor or joint inventor should further note that it is well established that the specification may not impose a further limitation upon the plain meaning of the claim language. As stated in the Supreme Court, [S]ome persons seem to suppose that a claim in a patent is like a nose of wax, which may be turned and twisted in any direction by merely referring to the specification, so as to make it include something more than or something different from what its words express. The context may undoubtedly be resorted to, and often is resorted to, for the purpose of better understanding the meaning of the claim, but not for the purpose of changing it and making it different from what it is. The claim is a statutory requirement, prescribed for the very purpose of making the patentee define precisely what his invention is, and it is unjust to the public, as well as an evasion of the law, to construe it in a manner different from the plain meaning of its terms. {See White v. Dunbar, 119 US 47, 51-52, 1886 CD 494, 497-498 (1886)}.
As a result of the Amendments to the Claims, filed August 20, 2026, and to clarify the record, the original rejections, made in the Non-Final Rejection, mailed on May 20, 2026, are amended below, in the section entitled New Claim Rejections - 35 U.S.C. § 112(b), to omit cancelled claims 18 and 19.
New Claim Objections
Claim 1 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(a) and/or 35 U.S.C. § 112(b), the existing recitation should be replaced with the following recitation:
A compound of the following formula:
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or a pharmaceutically acceptable salt thereof,
wherein:
X is -C(CH3)2-, -O-, or -Si(CH3)2-;
R1 is an affinity tag-containing moiety or a protein-manipulation moiety selected from the group consisting of:
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,
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,
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, and
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;
each R2 is independently H, D, halogen, CN, CF3, C(O)NH(alkyl), C(O)N(alkyl)2, C(O)OH, C(O)O(alkyl), N(alkyl)2, OH, O(alkyl), or S(O)2CH3;
each R3 is independently H or D;
each R4 is independently H, halogen, CN, or CF3;
(i) R5 is H, F, or C(O)OH; or
R5 is the self-labeling protein (SLP) ligand:
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;
(ii) R6 is H, F, or C(O)OH; or
R6 is the self-labeling protein (SLP) ligand:
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;
(iii) R7 is H, F, or C(O)OH; or
R7 is the self-labeling protein (SLP) ligand:
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; and
(iv) R8 is H, F, or C(O)OH; or
R8 is the self-labeling protein (SLP) ligand:
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;
with the proviso that one of R5, R6, R7, and R8 is the self-labeling protein (SLP) ligand:
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.
Appropriate correction is required. See MPEP § 2173.02.
Claim 2 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is:
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,
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, or
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.
Appropriate correction is required. See MPEP § 2173.02.
Claim 3 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(d), the claim is dependent upon a rejected base claim. Appropriate correction is required. See MPEP § 2173.02.
Claim 5 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein:
each R2 is independently H or F;
each R3 is independently H;
each R4 is independently H;
R5 is H;
R6 is H;
R7 is the self-labeling protein (SLP) ligand:
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; and
R8 is H.
Appropriate correction is required. See MPEP § 2173.02.
Claim 6 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 5, or a pharmaceutically acceptable salt thereof, wherein X is -Si(CH3)2- or -O-.
Appropriate correction is required. See MPEP § 2173.02.
Claim 7 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein X is -O- or -Si(CH3)2-.
Appropriate correction is required. See MPEP § 2173.02.
Claim 8 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(d), the claim is dependent upon a rejected base claim. Appropriate correction is required. See MPEP § 2173.02.
Claim 9 is objected to because of the following informalities: for brevity, clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The compound of claim 1, wherein the compound is of the following formula:
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,
or a pharmaceutically acceptable salt thereof,
wherein:
L is
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or
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; and
each R is independently H or F.
Appropriate correction is required. See MPEP § 2173.02.
Claim 10 is objected to because of the following informalities: for brevity, clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The compound of claim 1, wherein the compound is of the following formula:
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, or
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,
or a pharmaceutically acceptable salt thereof,
wherein:
X is -O-; and
each R is independently H or F.
Appropriate correction is required. See MPEP § 2173.02.
Claim 11 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, wherein the compound is selected from the group consisting of:
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or a pharmaceutically acceptable salt thereof.
Appropriate correction is required. See MPEP § 2173.02.
Claim 12 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, wherein the compound is selected from the group consisting of:
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, and
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or a pharmaceutically acceptable salt thereof.
Appropriate correction is required. See MPEP § 2173.02.
Claim 13 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, wherein the compound is:
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,
or a pharmaceutically acceptable salt thereof.
Appropriate correction is required. See MPEP § 2173.02.
Claim 14 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is:
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.
Appropriate correction is required. See MPEP § 2173.02.
Claim 17 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is:
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.
Appropriate correction is required. See MPEP § 2173.02.
New Claim Rejections - 35 U.S.C. § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. § 112:
(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.
Substituted rhodamines
Claims 1, 2, 4-7, 9 and 14-17 are rejected under 35 U.S.C. § 112(a) because the specification, while being enabling for substituted rhodamines, where R1 and SLP are as presented herein in the section above entitled New Claim Objections, does not reasonably provide enablement for substituted rhodamines, where R1 and SLP are not as presented herein in the section above entitled New Claim Objections. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims. Substituted rhodamines, where R1 and SLP are not as presented herein in the section above entitled New Claim Objections, as recited in claim 1, have not been adequately enabled in the specification to allow any person having ordinary skill in the art, at the time this invention was made, to make and/or use substituted rhodamines, where R1 and SLP are not as presented herein in the section above entitled New Claim Objections.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is undue. These factors include, but are not limited to: (a) breadth of the claims; (b) nature of the invention; (c) state of the prior art; (d) level of one of ordinary skill in the art; (e) level of predictability in the art; (f) amount of direction provided by the inventor or joint inventor; (g) existence of working examples; and (h) quantity of experimentation needed to make or use the invention based on the content of the disclosure. {See Ex parte Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986); and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988)}.
The above factors, regarding the instant invention, are summarized as follows:
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(a) Breadth of the claims - the breadth of the claims includes substituted rhodamines, shown to the right;
(b) Nature of the invention - the nature of the invention is evaluation of substituted rhodamines, shown to the right, and the pharmacokinetic behavior of these substances as fluorophores;
(c) State of the prior art - Nature Reviews: Drug Discovery, as provided in the file and cited in the Non-Final Rejection, mailed on May 20, 2026, offers a snapshot of the state of the drug development art. Herein, drug development is stated to follow the widely accepted Ehrlich model which includes: (1) development of a broad synthetic organic chemistry program; (2) subsequent testing of compounds in an appropriate laboratory model for the disease to be treated; and (3) screening of compounds with low toxicity in prospective clinical trials (Jordan, V. C. Nature Reviews: Drug Discovery, 2, 2003, 205). Moreover, US 11,091,643, as cited in the Non-Final Rejection, mailed on May 20, 2026, provides a synthesis of the instantly recited substituted rhodamines {Lavis, et al. US 11,091,643, 2021};
(d) Level of one of ordinary skill in the art - the artisans synthesizing the inventor’s or joint inventor’s substituted rhodamines, where R1 and SLP are not as presented herein in the section above entitled New Claim Objections, would be a collaborative team of synthetic chemists and/or health practitioners, possessing commensurate degree level and/or skill in the art, as well as several years of professional experience;
(e) Level of predictability in the art - Synthetic organic chemistry is quite unpredictable (See In re Marzocchi and Horton 169 USPQ at 367 ¶3). Similarly, it is unclear based on the combination of the instant specification, and Lavis, et al. in US 11,091,643, as cited in the Non-Final Rejection, mailed on May 20, 2026, whether the instantly recited substituted rhodamines, where R1 and SLP are not as presented herein in the section above entitled New Claim Objections, are enabled. Moreover, the following excerpt is taken from Dörwald, as provided in the file and cited in the Non-Final Rejection, mailed on May 20, 2026, which has relevance to the synthesis of substituted rhodamines, where R1 and SLP are not as presented herein in the section above entitled New Claim Objections (Dörwald, F. Zaragoza. Side Reactions in Organic Synthesis: A Guide to Successful Synthesis Design, Weinheim: WILEY-VCH Verlag GmbH & Co. KGaA, 2005, Preface):
Most non-chemists would probably be horrified if they were to learn how many attempted syntheses fail, and how inefficient research chemists are. The ratio of successful to unsuccessful chemical experiments in a normal research laboratory is far below unity, and synthetic research chemists, in the same way as most scientists, spend most of their time working out what went wrong, and why.
Despite the many pitfalls lurking in organic synthesis, most organic chemistry textbooks and research articles do give the impression that organic reactions just proceed smoothly and that the total synthesis of complex natural products, for instance, is maybe a labor-intensive but otherwise undemanding task. In fact, most syntheses of structurally complex natural products are the result of several years of hard work by a team of chemists, with almost every step requiring careful optimization. The final synthesis usually looks quite different from that originally planned, because of unexpected difficulties encountered in the initially chosen synthetic sequence. Only the seasoned practitioner who has experienced for himself the many failures and frustrations which the development (sometimes even the repetition) of a synthesis usually implies will be able to appraise such work.
Chemists tend not to publish negative results, because these are, as opposed to positive results, never definite (and far too copious).
(f) Amount of direction provided by the inventor - the invention lacks direction with respect to making and/or using substituted rhodamines, where R1 and SLP are not as presented herein in the section above entitled New Claim Objections;
(g) Existence of working examples - the inventor or joint inventor has provided sufficient guidance to make and/or use substituted rhodamines, where R1 and SLP are as presented herein in the section above entitled New Claim Objections; however, the disclosure is insufficient to allow extrapolation of the limited examples to enable the instantly recited substituted rhodamines, where R1 and SLP are not as presented herein in the section above entitled New Claim Objections. The specification lacks working examples of substituted rhodamines, where R1 and SLP are not as presented herein in the section above entitled New Claim Objections.
Within the specification, [A]t least one specific operative embodiment or example of the invention must be set forth. The example(s) and description should be of sufficient scope as to justify the scope of the claims. Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a chemical compound is stated only as a probability or speculation, the disclosure is not sufficient to support claims identifying the compound by such composition or formula. See MPEP § 608.01(p) and MPEP § 2173.05.
(h) Quantity of experimentation needed to make or use the invention based on the content of the disclosure - predicting whether a recited compound is in fact one that produces a desired physiological effect at a therapeutic concentration and with useful kinetics, is filled with experimental uncertainty, and without proper guidance, would involve a substantial amount of experimentation (Jordan, V. C. Nature Reviews: Drug Discovery, 2, 2003, 205-213). Similarly, the specification, as originally filed, including any references incorporated therein, fails to provide the necessary support required by 35 U.S.C. § 112(a) to enable the instantly recited substituted rhodamines, where R1 and SLP are not as presented herein in the section above entitled New Claim Objections. Thus, it is unclear, whether a substituted rhodamine, where R1 and SLP are not as presented herein in the section above entitled New Claim Objections, is either synthetically feasible or possesses utility as a fluorophore.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the invention was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. {See In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)}.
The determination that undue experimentation would have been needed to make and use the claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached by weighing all the above noted factual considerations. (See In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404). These factual considerations are discussed comprehensively in MPEP § 2164.08 (scope or breadth of the claims), § 2164.05(a) (nature of the invention and state of the prior art), § 2164.05(b) (level of one of ordinary skill), § 2164.03 (level of predictability in the art and amount of direction provided by the inventor or joint inventor), § 2164.02 (the existence of working examples) and § 2164.06 (quantity of experimentation needed to make or use the invention based on the content of the disclosure).
Based on a preponderance of the evidence presented herein, the conclusion that the inventor or joint inventor is insufficiently enabled for making and/or using substituted rhodamines, where R1 and SLP are not as presented herein in the section above entitled New Claim Objections, is clearly justified.
The examiner suggests amending the claims, particularly as stated in the section above entitled New Claim Objections, to overcome this rejection.
New Claim Rejections - 35 U.S.C. § 112(b)
The following is a quotation of the second paragraph of 35 U.S.C. § 112:
(b) CONCLUSION. The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or joint inventor regards as the invention.
Claims 1, 2, 5-7 and 14-17 are rejected under 35 U.S.C. § 112(b) as being indefinite for failing to set forth the subject matter which the inventor or joint inventor regards as the invention.
The inventor or joint inventor should note that the phrase, self-labeling protein (SLP) ligand, in claim 1, with regard to R5, R6, R7, and/or R8, respectively, is a relative phrase which renders the claim indefinite. The phrase, self-labeling protein (SLP) ligand, is not defined by the claim, the specification does not provide an adequate standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the invention. The specification, on page 14, uses open language, such as for example and include, to define the phrase, self-labeling protein (SLP) ligand, as HaloTag®, SNAP-tag®, TMP-tag®, bLac-tag®, CLIP-tag®, and biotin-avidin; however, neither the specification, nor the claim, explicitly limits the invention to any specifically disclosed or recited embodiments. Consequently, the instantly recited substituted rhodamines have been rendered indefinite by the use of the phrase, self-labeling protein (SLP) ligand, with regard to R5, R6, R7, and/or R8, respectively.
Moreover, the inventor or joint inventor should further note that [C]laims which depend from indefinite claims are also indefinite. {See Ex parte Cordova, 10 USPQ 2d 1949, 1952 (PTO Bd. App. 1989)}.
The examiner suggests amending the claims, particularly as stated in the section above entitled New Claim Objections, to overcome this rejection.
Claims 1, 4, 7, 9 and 14-17 are rejected under 35 U.S.C. § 112(b) as being indefinite for failing to set forth the subject matter which the inventor or joint inventor regards as the invention.
The inventor or joint inventor should note that the phrase, affinity tag-containing moiety, in claim 1, with respect to R1, is a relative phrase which renders the claim indefinite. The phrase, affinity tag-containing moiety, is not defined by the claim, the specification does not provide an adequate standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the invention. The specification, on page 12, uses open language, such as including, but not limited to, to define the phrase, affinity tag-containing moiety, as biotin and desthiobiotin for avidin-mediated capture, trimethoprim/folate/methotrexate for dihydrofolate reductase (DHFR)-mediated capture, a peptide epitope such as FLAG for antibody-mediated capture, or a click chemistry reagent such as azide, alkyne, tetrazine or dibenzocyclooctyne (DBCO) for biorthogonal capture; however, neither the specification, nor the claim, explicitly limits the invention to any specifically disclosed or recited embodiments. Consequently, the instantly recited substituted rhodamines have been rendered indefinite by the use of the phrase, affinity tag-containing moiety, with respect to R1.
The examiner suggests amending the claims, particularly as stated in the section above entitled New Claim Objections, to overcome this section of the rejection.
Similarly, the inventor or joint inventor should further note that the phrase, protein-manipulation moiety, in claim 1, with respect to R1, is a relative phrase which renders the claim indefinite. The phrase, protein-manipulation moiety, is not defined by the claim, the specification does not provide an adequate standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the invention. The specification, on page 12, uses open language, such as for example, to define the phrase, protein-manipulation moiety, as (+)-JQ1, blebbistatin, trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA), or MAK683; however, neither the specification, nor the claim, explicitly limits the invention to any specifically disclosed or recited embodiments. Consequently, the instantly recited substituted rhodamines have been rendered indefinite by the use of the phrase, protein-manipulation moiety, with respect to R1.
Moreover, the inventor or joint inventor should further note that [C]laims which depend from indefinite claims are also indefinite. {See Ex parte Cordova, 10 USPQ 2d 1949, 1952 (PTO Bd. App. 1989)}.
The examiner suggests amending the claims, particularly as stated in the section above entitled New Claim Objections, to overcome this section of the rejection.
Allowable Subject Matter
No claims are allowed.
Conclusion
The inventor’s or joint inventor’s arguments and/or the Amendments to the Claims, filed August 20, 2026, necessitated the new grounds of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). The inventor or joint inventor 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to DOUGLAS M. WILLIS, whose telephone number is 571-270-5757. The Examiner may normally be reached on Monday thru Thursday from 8:00-6:00 EST. The Examiner is also available on alternate Fridays.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Mr. Jeffrey Murray, may be reached on 571-272-9023. The fax phone number for the organization where this invention or proceeding is assigned is 571-273-8300.
Information regarding the status of an invention may be obtained from Patent Center. For more information about Patent Center, see https://www.uspto.gov/patents/apply/patent-center. Should you have questions on access to Patent Center, contact the Patent Electronic Business Center (PEBC) at 866-217-9197 (toll-free) or ebc@uspto.gov.
/DOUGLAS M WILLIS/
Primary Examiner, Art Unit 1624
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