DETAILED ACTION
The present application is being examined under the pre-AIA first to invent provisions.
Response to Amendment
An amendment filed on 27 January 2026 is acknowledged. Claims 13 and 22 are amended. Claims 13-16, 18-25, and 27-30 are pending and are presented for examination on the merits.
In response to the amendment filed on 27 January 2026, the objections to the claims are withdrawn; the rejections under 35 U.S.C. 112, second paragraph are modified and changed; the rejections over the prior art are changed; and double patenting rejections are added.
Claim Rejections - 35 USC § 112
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 13-16, 18-25, and 27-30 are 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 pre-AIA the applicant regards as the invention.
Claims 13 and 22 recite the limitations "R1 to R6 are independently selected from the group consisting of: […] alone or in combination"; "o, m and p are independently selected from the group consisting of: […] alone or in combination"; and "at least one substituent selected from the group consisting of: […] alone or in combination". The claimed selecting of options "in combination" is interpreted to mean that a single substituent can by characterized by a combination of the listed members of the group. This is indefinite for some of the possible combinations the listed members of the group, such as a single substituent being both halogen and "-(CH2)nCO2H," a single substituent being both hydrogen and anything else, or a single substituent being both halogen and cyano, or a single substituent being both halogen and azido.
Claims 13 and 22 recite the limitation "wherein a substituted alkenyl is substituted or unsubstituted ethenyl, substituted or unsubstituted dienyl, or substituted or unsubstituted trienyl." It is unclear how an unsubstituted ethenyl, dienyl, or trienyl is a substituted alkenyl.
Claims 13 and 22 recite the limitation "the substituted alkenyl." There is insufficient antecedent basis for this limitation because the claims introduce "substituted…alkenyl" twice before (in the definitions of both [i] R1 to R6 and [ii] o, m and p).
Claims 13 and 22 recite the limitation "where a substituted aryl is selected from substituted or unsubstituted phenyl, substituted or unsubstituted 1-naphthyl, substituted or unsubstituted 2-naphthyl, substituted or unsubstituted 1-pyrenyl, and substituted or unsubstituted 9-anthryl. It is unclear how the unsubstituted options are an example of a substituted aryl.
Claims 13 and 22 recite the limitation "where a substituted heteroaryl is selected from pyridyl and quinolyl. It is unclear how "pyridyl" is a substituted heteroaryl. It is unclear how "quinolyl" is a substituted heteroaryl.
Claims 13 and 22 recite the limitation "wherein a substituted aryl group..." It is unclear what relationship this limitation has to the other limitations of the claims.
A broad range or limitation together with a narrow limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claims 13 and 22 recite "a substituted aryl includes at least one substituent selected from the group consisting of halogen, -(CH2)nCO2H wherein n = 0 to 6, -(CH2)nCO2R wherein n = 0 to 6, alkyl having 1-5 carbon atoms, alkoxy having an alkyl portion with 1-4 carbon atoms," which is broad with respect to non-alkyl substituents and narrow with respect to the carbon number of an alkyl substituent. Claims 13 and 22 also recite "wherein a substituted aryl group includes a substituted or unsubstituted alkyl substituent…," which is narrower with respect to requiring an alkyl substituent and broader with respect to carbon number. The claim(s) are considered indefinite because there is a question or doubt as to whether the features introduced by narrower language are (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) required features of the claims.
Dependent claims 14-16, 18-21, 23-25, and 27-30 are rejected for inheriting deficiencies from independent claim 13 or 22.
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Dependent claims 15 and 24 recite that the dye is 4,4-difluoro-3,5-bis(4-methoxyphenyl)-8-(4-maleimidylphenyl)-4-bora-3a,4a-diaza-s-indacene. The structure is shown above, which corresponds to R1 and R6 of formula (I) to being 4-methoxyphenyl (phenyl substituted with an alkoxy substituent having an alkyl portion with 1 carbon atom). It is unclear whether claims 15 and 24 require all of the limitations of the independent claims, including the narrow limitation "wherein a substituted aryl group includes a substituted or unsubstituted alkyl substituent…"
Claim Interpretation
Claims 21 and 30 recite the term "polysaccharide." The specification provides the following relevant teaching ([00052], pages 16-17):
Mono- and poly-saccharides, such as sucrose, maltose, trehalose, dextrose and sorbitol, as well as well as a number of other polyols, such as glycerol, are known to stabilize various proteins in vitro. Any of the above referenced assay conditions may be used with dipyrrometheneboron difluoride dyes of formula (1) for protein melt assays.
Sucrose, maltose, and trehalose are disaccharides. Dextrose and sorbitol are monosaccharides. The specification does not provide a special definition of "polysaccharide." However, the above passage of the specification uses specific disaccharides as examples of polysaccharides. As set forth in the last office action, the IUPAC defines "polysaccharides" as follows:
Compounds consisting of a large number of monosaccharides linked glycosidically. This term is commonly used only for those containing more than ten monosaccharide residues. Also called glycans.
This narrow definition excludes disaccharides. However, Merriam-Webster Online Dictionary provides a broader definition that is inclusive of disaccharides, although a narrower meaning especially characterizes the term:
: a carbohydrate that can be decomposed by hydrolysis into two or more molecules of monosaccharides; especially : one (as cellulose, starch, or glycogen) containing many monosaccharide units and marked by complexity
In view of the examples provided by the instant specification and the broad definition provided by Merriam-Webster Online Dictionary, the claimed term "polysaccharide" is interpreted as encompassing disaccharides such as sucrose.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of pre-AIA 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 –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claims 13, 15, 16, 18, 19, 22, 24, 25, 27, and 28 are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by Maaty ("Something Old, Something New, Something Borrowed; How the Thermoacidophilic Archaeon Sulfolobus solfataricus Responds to Oxidative Stress," PLoS ONE 2009; newly cited).
On page 4 (Protein thiol reactivity), Maaty discloses the following (bolding added):
S. solfataricus cells H2O2-treated for 0, 30 or 105 min were resuspended in PBS (pH 7.4). Cells were lysed by sonication (three, 30 sec cycles at 50% duty cycle with a power output of 2; Branson Sonifier); the protein supernatants were clarified by centrifugation at 20,000×g for 12 min at 4°C and collected. The cell lysates were labeled with the fluorescent sulfhydryl-modifying reagent 4,4-difluoro-3,5-bis(4-methoxyphenyl)-8-(4-maleimidylphenyl)-4-bora-3a,4a-diaza-s-indacene (BODIPY® 577/618 maleimide; Invitrogen). The reagent concentration was adjusted to 1 mg/ml and the reaction was carried out for 2 hours in the dark in the presence of 1% SDS. Samples were mixed with 4×SDS sample buffer (non-reducing conditions) before separation over mini 4–20% gradient SDS-PAGE gel. Labeled mixtures were run on SDS gel in triplicate. Fronts were run off the gels to remove unreacted dye and obtain cleaner fluorescence images.
Regarding claims 13, 15, 22, and 24, Maaty discloses a composition comprising:
at least one surfactant that is an anionic surfactant (sodium dodecyl sulfate, SDS, page 4, para. bridging cols.), and
a dye of formula (I), wherein the dye is 4,4-difluoro-3,5-bis(4-methoxyphenyl)-8-(4-maleimidylphenyl)-4-bora-3a,4a-diaza-s-indacene (BODIPY® 577/618 maleimide, page 4, para. bridging cols.; compare to compound 1b of instant specification on page 3 copied below).
The indefinite narrow limitation "wherein a substituted aryl group includes a substituted or unsubstituted alkyl substituent…" of independent claims 13 and 22 is not given weight for purposes of this rejection. The dye disclosed by Maaty is the same dye recited in dependent claims 15 and 24 and corresponds to formula (I), where R1 and R6 are each 4-methoxyphenyl, which is phenyl substituted with an alkoxy substituent having an alkyl portion with 1 carbon atom.
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Regarding the term “kit” recited in the preamble of independent claim 22, a preamble is generally not accorded any patentable weight where it merely recites the intended use of a structure, and where the body of the claim does not depend on the preamble for completeness but, instead, the structural limitations are able to stand alone. See In re Hirao, 535 F.2d 67, 190 USPQ 15 (CCPA 1976) and Kropa v. Robie, 187 F.2d 150, 152, 88 USPQ 478, 481 (CCPA 1951).
Regarding claims 16 and 25, Maaty discloses that the composition or kit further comprises a buffer ("PBS," "sample buffer"; page 4, para. bridging cols.).
Regarding claims 18 and 27, Maaty discloses that the cell lysates were combined with BODIPY® 577/618 maleimide in the presence of 1% SDS (page 4, para. bridging cols.). The examiner takes official notice that a concentration of sodium dodecyl sulfate of 1% is at or above the critical micelle concentration.
Regarding claims 19 and 28, Maaty discloses that the kit further comprises a polyol (protein from S. solfataricus cells, page 4, para. bridging cols., which contain plural amino acid residues such as serine, threonine, and tyrosine that each have a hydroxyl group).
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 14 and 23 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Maaty in view Molecular Probes Handbook (Thiol-Reactive Probes, Chapter 2, 2010, IDS; previously relied upon).
Regarding claims 14 and 23, Maaty does not disclose that the dye is 4,4-difluoro-1,3,5,7-tetramethyl-8-(4-maleimidylphenyl)-4-bora-3a,4a-diaza-s-indacene (i.e., BODIPY® 499/508 maleimide; see page 3 of instant specification for structure). Maaty instead discloses BODIPY® 577/618 maleimide from Invitrogen for labeling protein thiol groups (page 4, para. bridging cols.).
In the analogous art of fluorescent maleimide probes, Molecular Probes Handbook discloses 4,4-difluoro-1,3,5,7-tetramethyl-8-(4-maleimidylphenyl)-4-bora-3a,4a-diaza-s-indacene (Fig. 2.2.6A, page 106, copied below).
Molecular Probes Handbook teaches that this thiol-reactive dye is commercially available as BODIPY® 499/508 maleimide (D20350) from Invitrogen by Thermo Fisher Scientific (ibid.). The selection of a known material, which is based upon its suitability for the intended use, is within the ambit of one of ordinary skill in the art. See In re Leshin, 125 USPQ 416 (CCPA 1960) (see MPEP § 2144.07). The simple substitution of one known element for another is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, B.).
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For the benefit of labeling a protein with a dye having different excitation/emission maxima, it would have been obvious to one of ordinary skill in the art at the time of the invention to substitute BODIPY® 499/508 maleimide, as disclosed in the Molecular Probes Handbook, for the BODIPY® 577/618 maleimide disclosed by Maaty.
Claims 19-21 and 28-30 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Maaty in view of Diller (US 2009/0035868, IDS; previously relied upon).
Regarding claims 19-21 and 28-30, Maaty does not disclose that the composition or kit comprises a polyol that is glycerol or a polysaccharide. (This rejection of claims 19 and 28 is based on an alternative interpretation of polyol compared to the rejections of claims 19 and 28 for anticipation by Maaty.)
In the analogous art of labeling proteins with a thiol reactive fluorescent dye (abstract, [0003], [0048]), in which the labeling compound comprises a thiol-reactive group that is maleimide ([0094]), Diller discloses use of a sugar alcohol such as glycerol or sucrose during the protein labeling ([0141], [0215], [0222]). Diller teaches that this is useful for separation of the labeled proteins or mixtures of labeled proteins using slab gel electrophoretic techniques ([0141]).
For the benefit of separation of the labeled protein mixture using slab gel electrophoretic techniques, it would have been obvious to one of ordinary skill in the art at the time of the invention to modify the labeling method of Maaty with Diller's method of using a polyol that is glycerol or sucrose during the labeling reaction, as taught by Diller. As set forth above in the claim interpretation section, the "polysaccharide" of claims 21 and 30 is interpreted as encompassing disaccharides such as sucrose.
The use of a known technique to improve similar devices (methods or products) in the same way is likely to be obvious. See KSR International Co. v. Teleflex Inc., 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, C.).
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 13-16, 19-25, and 28-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 9,568,478 (IDS). Although the claims at issue are not identical, they are not patentably distinct from each other.
The pending claims are broader than the patented claims because the pending claims do not require "at least one protein" and because the pending claims recite "at least one surfactant selected from the group consisting of an alkyl saccharide surfactant, an anionic surfactant…" The patented claims recite methyl ester sulfonate (MES) and dodecyl-β-D-maltoside (DDM), which are respectively an example of an anionic surfactant and an alkyl saccharide surfactant.
Response to Arguments
Applicant's arguments filed on 27 January 2026 have been considered and are not fully persuasive and/or are moot in view of the new grounds of rejection.
Applicant's arguments do not specifically address the modified grounds of rejection under 35 U.S.C. 112, second paragraph.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHELLE ADAMS whose telephone number is (571)270-5043. The examiner can normally be reached M, T, Th, and F, 12-4 P.M.
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, Lyle Alexander can be reached on (571) 272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MICHELLE ADAMS/Examiner, Art Unit 1797
/JENNIFER WECKER/Primary Examiner, Art Unit 1797
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