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 .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Status of Claims
Claims 1-20 are pending. Claims 6-11 and 14-19 are drawn to the nonelected group. Claims 1-5, 12-13 and 20 are under examination.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-5, 12-13 and 20) in the reply filed on 07/14/2025 is acknowledged. Furthermore, Applicant has elected Cy5 as Species 1-A and HRP-conjugated monoclonal antibody (Species 1-B).
Claims 6-11 and 14-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse.
Claim Objections
Claim 2 is objected to because of the following informalities: The claim recites “(labeled with tetramethylrhodamine or “TMR”) should be – (tetramethylrhodamine) – to be consistent with TAMRA. Additionally, at least one “BODIPY” should be accompanied with an unabbreviated IUPAC name. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claims 1-4, 12-13, and 20 are 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(s) 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.
MPEP § 2163 states that, for a claimed genus, the written description requirement may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus:
The claim is drawn a compound having formula (I) and R comprises a detector marker.
The claim as a whole covers a genus of compounds containing formula (I) and detectable marker. Meanwhile, the specification only discloses cleavable fluorescent tyramide (CFT) and protein targets are stained with HRP conjugated to antibodies and CFT and subsequently, the fluorophores are efficiently cleaved by mild chemical reagents, which simultaneously deactivate HRP and demonstrated that over 95% of the staining signals can be erased by mild chemical reagents while preserving the integrity of the epitopes on the protein targets (see para. [0071], as filed). The specification has not provided Examples of any other detectable marker other than fluorophores to be conjugated (i.e., represented by R group) with formula (1). Although the specification has listed quantum dots, fluorescent proteins, and radioisotopes, the specification has not provided Examples on how these structures are able to be cleaved in such as way that can be erased by mild chemical reagents while preserving the integrity of the protein targets and simultaneously deactivate HRP. The only R structures that are conjugated to the cleavable group of formula (I) are structures of fluorophores.
In particular, Columbia Biosciences teaches that fluorescent protein such as phycobiliproteins and these fluorescent proteins are larger than in size than those using small molecules dyes and phycobiliproteins such as RPE conjugate can often be large enough to affect and limit their consistent penetration of the permeabilized cell membrane (see page 2, right col., para. 1). Also, aggregation of proteins in their native form can lead to high nonspecific binding and background (see page 2, left col., para. 1). Columbia Biosciences teaches that quality and integrity of the detection components used in conjugates can make a big difference when it counts at detection time (see page 2, left col., para. 1) (Columbia Biosciences, https://columbiabiosciences.com/whitepaper-what-makes-a-good-conjugate-great-2/, print retrieve on 10/10/2025).
As stated above, the MPEP has stated that written description for a genus can be achieved by a representative number of species within a broad generic limitation. However, it is unquestionable that these claims are broad and generic with respect to “a compound having” and what is being conjugated to the cleavable group of formula (1). The possible structural variations are limitless. Meanwhile, the skilled artisan would not be able to envision any larger compound comprising formula (1) nor conjugating the cleavable group of formula (1) with quantum dots, fluorescent proteins and radioisotopes without at least an Example (i.e., not just listed in the disclosure). As stated above, Columbia Biosciences teaches that quality and integrity of the detection components used in conjugates can make a big difference when it counts at detection time. Meanwhile, the specification has not provided examples or structures of the cleavable group of formula (I) conjugating to molecules other than fluorophores.
In light of the specification, the person skilled in the art would face an undue burden of examination in extrapolating from the myriad of combinations of the claimed compounds. The person cannot envision the detailed chemical structures until reduction to practice has occurred, regardless of the simplicity of the product.
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 agents.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2, 4-5, 12-13 and 20 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.
Claims 2 and 4 contain the trademark/trade names (e.g., ATTO-TEC, ALEXA FLUORTM and DYLIGHTTM dyes). Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the claim scope is uncertain since the trademark or trade name cannot be use properly to describe any particular material or product (See MPEP 2173.05(u)). Applicant are suggested to amend claims 2 and 4 to delete any trademark or trade names present in the claims to overcome the rejection.
Additionally, claim 2 recites limitations of “(e.g.,…and the like)” render the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Also, recitations within the parentheses (labeled with tetramethylrhodamine or “TMR”) and (ATTO-TEC, Germany) are unclear to whether these limitations are part of the claimed compounds.
Claim 5 recites the chemical structure of Formula (II) but part of the chemical structure is faded out (i.e., different contrast). Therefore, it is unclear if whether the faded part of the chemical structure is optional recitation or required by formula (II). To overcome this rejection, the compound of formula II should be fully represented without contrast in color.
Claim 12 recites a kit comprising a composition comprising the compounds of “Formula I or Formula II” have not been clearly defined in the claim and it is unclear what Applicant is attempting to claim as the compound. Therefore, the claims are considered indefinite. Applicants are suggested to amend claim 12 to include the structures of formulas I and II with the variable definitions found in claims 1 and 5. Claims 13 and 20 are rejected as being dependent from claim 12.
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.
Claims 1-5, 12-13 and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pham et al. (“Multiplexed In Situ Protein Profiling with High-Performance Cleavable Fluorescent Tyramide”, Molecules, vol. 26, 2206, pgs. 1-16, published 04/12/2021, IDS submitted 11/29/2023, cite no. 20).
With respect to claims 1-5, Pham teaches cleavable fluorescent tyramide (CFT) (abstract). Pham further teaches tyramide-N3-Cy5 (see pg. 3, para. 1). Fig. 1B shows the cleavable fluorescent tyramide, tyramide-N3-Cy5 (see below):
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With respect to claim 12, Pham further teaches 1,3,5-triaza-7-phosphaadamantane (PTA) and TCEP at 40C (see pg. 2, para. 2).
Pham does not employ the specific terminology of a “kit” in describing their invention. However, as noted above, the reference teaches the elements of (a)-(c), which are the constituent compositions of the kit. This terminology of a “kit” does not clearly invoke any additional ingredients or provide antecedent basis for terms appearing in the body of the claim (such as specific packaging or container elements, for example). Consequently, when the claims are given their broadest reasonable interpretation, the teachings of Pham are anticipatory even though the reference does not employ the word "kit" in describing their invention, as the reference teaches all necessary compositions of the claimed “kit”. See also MPEP 2111.02.
With respect to claims 13 and 20, Pham further teaches horseradish peroxidase (HRP) conjugated antibodies and CFT (see abstract), which could be polyclonal or monoclonal antibody.
Additionally, Pham does not employ the specific terminology of a “kit” in describing their invention. However, as noted above, the reference teaches the elements of (a)-(d), which are the constituent compositions of the kit. This terminology of a “kit” does not clearly invoke any additional ingredients or provide antecedent basis for terms appearing in the body of the claim (such as specific packaging or container elements, for example). Consequently, when the claims are given their broadest reasonable interpretation, the teachings of Pham are anticipatory even though the reference does not employ the word "kit" in describing their invention, as the reference teaches all necessary compositions of the claimed “kit”. See also MPEP 2111.02.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-5, 12-13, and 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 and 15-17 of U.S. Patent No. 12385924B2 (‘924).
With respect to instant claim 1, although the claims at issue are not identical, they are not patentably distinct from each other because patent No. ‘924 recites the same instant compound of Formula (1) wherein R is a detectable marker selected from the group consisting of fluorophores, luminescent agents, fluorescent proteins, and radioisotopes. The instant claim 1 differs from the Patent claim 1 in that the Patent recites a compound of Formula (I) and R is a detectable marker. However, it would have been obvious to the person of ordinary skill in the art at the time of filing to have produced the instant claims because the instant claims encompass the structure of the claimed Patent.
With respect to instant claims 2 and 4, Patent claims 2 and 4 recite the instant claimed detectable markers.
With respect to instant claim 3, Patent claim 3 recites the instant claimed detectable marker.
With respect to instant claim 5, Patent claim 5 recites the instant claimed Formula (II).
With respect to instant claims 12-13 and 20, Patent claims 15-17 recite the claimed kit with the compositions.
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 1-5 and 12-13 are provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 1-5 and 12-13 of copending Application No. 19/246133 (reference application). The instant claims recite the same limitations as copending Application 19/246133.
This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
Conclusion
No claim is allowed.
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/N.P.N/Examiner, Art Unit 1678
/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678
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