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 .
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.
Priority
The present application claims benefit under 35 U.S.C. 119(e) to provisional application 63/521,692 filed on 6/18/2023.
Specification
The disclosure is objected to because of the following informalities:
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code in paragraph 91. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Appropriate correction is required.
Claim Objections
Claims 4 objected to because of the following informalities:
In claim 4 lines 2-3, “the plurality of functionalized inorganic nanoparticles” appears to be a typographical error, namely it is suggested that “the plurality of functionalized inorganic nanoparticles” read as “the plurality of fluorescent functionalized inorganic nanoparticles” (emphasis added) as per claim 1.
In claim 4 lines 2-3, “the functionalized inorganic nanoparticles” appears to be a typographical error, namely it is suggested that “the functionalized inorganic nanoparticles” read as “the plurality of fluorescent functionalized inorganic nanoparticles” (emphasis added) as per claim 1.
In claim 5 line 1, “The method of claim 1, further comprises,” appears to be a typographical error, namely it is suggested that “The method of claim 1, further comprises,” read as “The method of claim 1, further comprising:” (annotations added).
In claim 5 line 3, “by mixing a plurality of second linker molecules to the fluorescent” appears to be a typographical error, namely it is suggested that “by mixing a plurality of second linker molecules to the fluorescent” read as “by mixing a plurality of second linker molecules with the fluorescent” (annotations added).
In claim 19 line 4, “a Biotins” appears to be a typographical error, namely it is suggested that “a Biotins” read as “
In claim 21 lines 4-5, “; or a Heck, Mcmurray and Knoevenagel, Wittig, Homer reaction” appears to be a typographical error, namely it is suggested that “; or a Heck, Mcmurray and Knoevenagel, Wittig, Homer reaction” read as “ reaction, a Mcmurray reaction, a Knoevenagel reaction, a Wittig reaction, or a Homer reaction” (annotations added).
In claim 23 line 5, “a Biotins” appears to be a typographical error, namely it is suggested that “a Biotins” read as “
In claim 23 line 7, “an a methyltetrazine” appears to be a typographical error, namely it is suggested that “an a methyltetrazine” read as “and a methyltetrazine” (annotation added).
Appropriate correction is required.
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 3, 9, 12, 16-17, 19 and 23 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites “a) covering a surface of a plurality of inorganic nanoparticles with a functional group R using a coupling agent to form a plurality of functionalized inorganic nanoparticles”.
Dependent claim 3 recites “wherein coupling fluorescent dyes to the functionalized inorganic nanoparticles further comprises, mixing fluorescent dyes attached to the functional group R with functionalized inorganic nanoparticles”.
Claim 3 is indefinite because it is not clear how the fluorescent dyes attached to the functional group R would be able to couple to the functionalized inorganic nanoparticles given that the surface of the functionalized inorganic nanoparticles are covered with a functional group R. How can functional group R allow coupling of a dye with functional group R? A functional group is not expected to react with itself. The specification suggests that the functional group attached to the fluorescent dyes is not R, but a functional group that reacts with R, such as: “mercapto-Functionalized silica nanoparticles” and “maleimide-cFluor V 420 dye” (para. 116); “aminopropyl-Functionalized silica nanoparticles” and “NHS-cFluor UV388 dye” (para. 125); “amino-Functionalized silica nanoparticles” and “NHS-cFluor B532 dye” (para. 136); “amino-Functionalized silica nanoparticles” and “NHS-cFluor R780 dye” (para. 144). Therefore, a person having ordinary skill in the art would not be capable of recognizing the metes and bounds of the claim.
Claim 8 recites “wherein: the plurality of inorganic nanoparticles are covered with an inorganic metal oxide”.
Claim 9 recites “The method of claim 8, wherein: the plurality of inorganic nanoparticles include alumina nanoparticles, silica nanoparticles, titania nanoparticles, indium tin oxide nanoparticles, zinc oxide nanoparticles, iron oxide nanoparticles, antimony tin oxide nanoparticles, or nanoparticles covered with an inorganic metal oxide layer” (emphasis added).
Dependent claim 9 is unclear because it requires the plurality of inorganic nanoparticle be covered with an inorganic metal oxide (claim 8), while at the same time reciting the option (“or”) of covering the nanoparticle with an inorganic metal oxide layer. Dependent claim 9 as currently recited suggests that the nanoparticles are optionally covered with an inorganic metal oxide, which is contrary to what is recited in claim 8. Note that claim 9 contains all the limitations of claim 8, therefore, a person having ordinary skill in the art would be confused by the optional limitation in claim 9. For this reason the claim is rejected under 112b.
Claims 12, 19 and 23 recite “sulfonate (tosyl, mesyl)”. It is unclear whether the limitations in the parenthesis are limiting the sulfonate or merely exemplary. Furthermore, it is not clear what the relationship between “sulfonate” and “tosyl” and “mesyl” is because tosyl and mesyl are not sulfonates. Does Applicant mean tosylate and mesylate? For these reasons a person having ordinary skill in the art would not be capable of recognizing the scope of the claim.
Claim 16 contains the trademark/trade name BODIPY (line 2) and ATTO (line 3). 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 trademark/trade name is used to identify/describe fluorescent dyes and, accordingly, the identification/description is indefinite. A person having ordinary skill in the art would not be capable of recognizing the metes and bounds of the claim.
Claim 17 recites “a narrow bandwidth”
The term “narrow” in claim 17 is a relative term which renders the claim indefinite. The term “narrow” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is not clear what bandwidth is encompassed by the term “narrow”; thus, a person having ordinary skill in the art would not be capable of recognizing the metes and bounds of the claim.
Claim 19 recites “The method of claim 18, wherein: the functional groups on the fluorescent dyes is at least one of an amino, an alkylhalide,…and a methyltetrazine and other reactive functional groups”.
However, the limitation “and a methyltetrazine and other reactive functional groups” is not clear. The limitation of “and other reactive functional groups” may be interpreted in multiple ways. For example, the claim suggests that the list of functional groups ends with “and a methyltetrazine”, therefore, “and other reactive functional groups” may be interpreted as an added reactive functional group, i.e. at least one of the functional groups from the list plus another functional group. Another possible interpretation is that “and other reactive functional groups” refers to one of the possible functional groups on the fluorescent dye. Because of this, a person having ordinary skill in the art would not be capable of recognizing the metes and bounds of the claim.
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 1-26 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yamanaka et al. (JP 2014153057 A) (“Yamanaka”) as evidenced by Vector Labs 5(6)-TAMRA NHS ESTER (retrieved online https://vectorlabs.com/products/56-tamra-nhs-ester/?print-products=pdf&srsltid=AfmBOor6Y-7npJFve1WrnbuNtU22zUvTNMkxyD39s43yslCxffBybeDu on 9/11/2026).
Regarding claim 1, Yamanaka teaches a method for producing conjugated inorganic nanoparticle fluorescent dye complexes for flow cytometry and biological applications (“METHOD OF MANUFACTURING LABELED ANTIBODY” Title, “The labeled antibody thus obtained can be used as an analysis reagent such as various diagnostic reagents and test reagents” page 2 para. 6, “The present invention relates to a method for producing a labeled antibody in which an antibody is bound to the surface of a silica nanoparticle” page 1 para. 5), the method comprising: a) covering a surface of a plurality of inorganic nanoparticles with a functional group R using a coupling agent to form a plurality of functionalized inorganic nanoparticles (“A functional molecule-containing silica nanoparticle is a product (an organoalkoxysilane with a functional molecule bound) in which the functional molecule and the silane coupling agent are bound by covalent bond, ionic bond or other chemical bond or physical adsorption The product can be obtained, and this product and one or more silane compounds (siloxane components) can be prepared, for example, by hydrolysis and condensation polymerization in a solvent containing aqueous ammonia to form a siloxane bond… The silane compound (siloxane component) is not particularly limited. For example,… γ-mercaptopropyltrimethoxysilane (MPS),… when the thing which has thiol groups, such as MPS, is used as said silane compound, since a thiol group will exist on the surface of the functional molecule containing silica nanoparticle obtained” bridge paragraph pages 2-3); b) coupling fluorescent dyes to the plurality of functionalized inorganic nanoparticles to form a plurality of functionalized fluorescent inorganic nanoparticles (“a labeled antibody in which an antibody is bound to the surface of a silica nanoparticle (hereinafter also referred to as a functional molecule-containing silica nanoparticle) containing a functional molecule such as a fluorescent dye” page 1 para. 3, “The “functional molecule” in the functional molecule-containing silica nanoparticle is not particularly limited, but it is preferable to use a labeled molecule which can be a detection indicator in an analysis reagent or the like. As the functional molecule, a fluorescent molecule” page 2 para. 7, “When a functional molecule and a silane coupling agent are covalently bonded, for example, N-hydroxysuccinimide (NHS) ester group… where the functional molecule is a fluorescent molecule is 5- (and -6) -carboxytetramethylrhodamine-NHS ester (trade name, emp Biotech GmbH) Products, DY550-NHS ester represented by the following formula, DY630-NHS ester…When the functional molecule has a succinimide group, it can be bonded to a silane coupling agent having an amino group” page 3 paras. 2-4 ); c) coupling a plurality of first linker molecules, attached to a functional group R", to the plurality of fluorescent functionalized inorganic nanoparticles (“The linker molecule used in the present invention is not particularly limited as long as it has a maleimide group and an amino group in the molecule…In the production method of the present invention, first, a thioether bond is formed between the maleimide group of the above-mentioned linker molecule and the thiol group introduced on the surface of the functional molecule-containing silica nanoparticle” page 5 paras. 3-4); and d) bioconjugating the plurality of fluorescent functionalized inorganic nanoparticles with antibodies or other bioactive molecules (“By attaching an antibody to the functional molecule-containing silica nanoparticle to which a linker molecule is prepared, prepared as described above, the functional molecule-containing silica nanoparticle to which an antibody is attached is produced” page 5 para. 6). Note that the limitation “for flow cytometry and biological applications” appears to be mere intended use of the recited nanoparticle and thus not required to by explicitly taught in the prior art in order to address the claim over the art. Nevertheless, although Yamanaka fails to use the language “for flow cytometry”, the teachings of using the nanoparticle conjugate as “an analysis reagent such as various diagnostic reagents and test reagents” inherently provides “for flow cytometry” because analysis reagents, test reagents and diagnostic reagents are routinely used in flow cytometry, and thus are expected to be capable of being used for flow cytometry.
Regarding claim 2, Yamanaka teaches wherein using the coupling agent to cover the surface of the plurality of inorganic nanoparticles with functional groups further comprises, hydrolyzing the coupling agent (“by hydrolysis” page 2 para. 8).
Regarding claim 3, although the claim is indefinite (see 112b rejection above), in the interest of compact prosecution, the functional group R attached to the fluorescent dyes is interpreted to be a functional group that reacts with functional group R.
Yamanaka teaches wherein coupling fluorescent dyes to the functionalized inorganic nanoparticles further comprises, mixing fluorescent dyes attached to the functional group R with functionalized inorganic nanoparticles (page 2 para. 7, “When a functional molecule and a silane coupling agent are covalently bonded, for example, N-hydroxysuccinimide (NHS) ester group, maleimide group, isocyanate group, isothiocyanate group, aldehyde group, paranitrophenyl group, di- A silane coupling agent having a functional molecule having an active group such as an ethoxymethyl group, an epoxy group, a cyano group and the like and a functional group (for example, an amino group, a hydroxyl group, a thiol group etc.) capable of reacting with these active groups be able to” page 3 para. 2).
Regarding claim 4, Yamanaka teaches wherein coupling a plurality of first linker molecules to the surface of the plurality of functionalized inorganic nanoparticles further comprises, mixing the plurality of first linker molecules, attached to a functional group R' and a functional group R", with the functionalized inorganic nanoparticles, wherein the functional group R' reacts with the functional group R covering the surface of a plurality of inorganic nanoparticles (“The linker molecule preferably has one maleimide group and one amino group” page 5 para. 3, “In the production method of the present invention, first, a thioether bond is formed between the maleimide group of the above-mentioned linker molecule and the thiol group introduced on the surface of the functional molecule-containing silica nanoparticle… The reaction of the maleimide group with the thiol group can be carried out in water or a buffer when the linker molecule to be used is a salt such as hydrochloride. When the linker molecule used is not a salt, it is carried out in an aprotic solvent…The aprotic solvent is not particularly limited as long as the silica nanoparticles can be dispersed… in the production method of the present invention, the maleimide group may be reacted with the thiol group of the functional molecule-containing silica nanoparticle” page 5 para. 4, “The reaction temperature is preferably 0 to 60 ° C, more preferably 0 to 40 ° C. The reaction time is preferably 5 minutes or more, more preferably 5 to 120 minutes” page 5 para. 5). Note that although Yamanaka fails to use the language “mixing”, the teaching of reacting the linker molecule with the particle in a buffer solution or a solvent such that the nanoparticles are dispersed and at temperatures of 60 degrees Celsius for 120 minutes inherently provides a step of mixing because these experimental conditions effectively cause the mixing of the two reagents. The temperature and time of the reaction would cause nanoparticles to diffuse throughout the solution and mix with the linker.
Regarding claim 5, Yamanaka teaches further comprises, changing the functional group R", attached to the plurality of first linker molecules, to a functional group R2, by mixing a plurality of second linker molecules to the fluorescent functionalized inorganic nanoparticles, wherein a functional group of the plurality of second linker molecules reacts with the functional group R" of the plurality of first linker molecules to form the functional group R2 (“the above antibody and carbodiimide to be described later are allowed to coexist in an aqueous solvent to form a carboxyl group of the antibody by active esterification, and an amide bond is formed between this active ester and the amino group of the linker molecule. Let This binding reaction is also carried out in an aqueous solvent. The active esterification of the carboxyl group possessed by the antibody by mixing the antibody and the carbodiimide may be performed before mixing with the functional molecule-containing silica nanoparticle to which the antibody and the linker molecule are bound, or may be performed after the mixing” page 5 para. 6). Note that although Yamanaka fails to use the language “second linker molecule” the teaching of changing the amino group of the linker with a carbodiimide to produce a carboxyl group inherently provides the use of a second linker molecule to change R" to R2.
Regarding claim 6, Yamanaka teaches further comprising: reacting linker molecules or oligomers with a plurality of antibodies or other bioactive molecules to activate the plurality of antibodies or other bioactive molecules (page 5 para. 6, “There is no restriction | limiting in particular as said carbodiimide, What is usually used for active esterification of a carboxyl group can be employ | adopted. For example, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide can be used. Moreover, N-hydroxy succinimide, sulfo N-hydroxy succinimide, etc. may coexist with a carbodiimide, and the active ester group produced | generated by carbodiimide may be derivatized to a more stable active ester group” page 6 para. 4).
Regarding claim 7, Yamanaka teaches directly bio-conjugating functionalized fluorescent inorganic nanoparticles with activated antibodies or other bioactive molecules (“The active esterification of the carboxyl group possessed by the antibody by mixing the antibody and the carbodiimide may be performed… simultaneously with the mixing” bridge paragraph pages 6-7). Note that although Yamanaka fails to use the language “directly bio-conjugating” the teaching of simultaneously mixing the active antibody with the nanoparticle inherently provides a direct bioconjugation of the nanoparticle and the activated antibodies.
Regarding claims 8-9, Yamanaka teaches wherein: the plurality of inorganic nanoparticles are covered with an inorganic metal oxide, wherein: the plurality of inorganic nanoparticles include silica nanoparticles (“silica nanoparticle” page 1 para. 5). Note that silica is reasonably interpreted as a metal oxide (silicon oxide).
Regarding claims 10, Yamanaka teaches wherein: a size of the plurality of inorganic nanoparticles is less than 500 nanometers, 200 nanometers, 100 nanometers, 50 nanometers, 25 nanometers, 15 nanometers, 10 nanometers, or 5 nanometers (“Moreover, it is preferable that it is 1-1000 nm, and, as for an average particle diameter, it is more preferable that it is 20-500 nm” page 3 para. 5).
Regarding claim 11, Yamanaka teaches wherein: the coupling agent is a silane coupling agent (“silane coupling agent” page 2 para. 8).
Regarding claim 12, Yamanaka teaches wherein: the functional group R on the coupling agent includes one or more of amino, mercapto (“γ-mercaptopropyltrimethoxysilane (MPS)… γ-aminopropyltriethoxysilane (APS)” page 3 para. 1).
Regarding claim 13, Yamanaka teaches wherein: the coupling agent comprises a silicon atom (“silane coupling agent …MPS” bridge paragraph pages 2-3); and the plurality of first linker molecules that connect the functional group R" to the silicon atom includes an alkyl chain (“a divalent aliphatic group or an arylene group or a combination thereof Preferably, they are linked molecules. The carbon number of the divalent aliphatic group is preferably an integer of 1 to 20” page 5 para. 3, “linker molecules having different carbon chain lengths” page 7 para. 3).
Regarding claim 14, Yamanaka teaches wherein: a number of repeated units of the plurality of first linker molecules ranges from 20 to 1 (“The linker molecule used in the present invention is not particularly limited as long as it has a maleimide group and an amino group in the molecule, but the maleimide group and the amino group may be a divalent aliphatic group or an arylene group or a combination thereof Preferably, they are linked molecules. The carbon number of the divalent aliphatic group is preferably an integer of 1 to 20, and more preferably an integer of 2 to 10” page 5 para. 3).
Regarding claim 15, Yamanaka teaches wherein: the fluorescent dyes is a fluorescent chemical compound that can emit light upon laser excitation (“fluorescent dye” page 1 para. 3, “(Detection device) has a detection unit consisting of a light source… a laser diode with a light source of 532 nm, and the sample is irradiated with a laser diode, and the reflected light is transmitted through an optical filter that transmits only light of a wavelength of 550 nm or more. Light receiving mechanism” page 11 para. 5).
Regarding claim 16, Yamanaka teaches wherein: the fluorescent dyes is at least one of a Cyanine derivatives, Rhodamine derivatives (“5- (and -6) -carboxytetramethylrhodamine-NHS ester…DY550-NHS ester… DY630-NHS ester” page 3 para. 3).
Regarding claim 17, Yamanaka teaches wherein: the fluorescent dyes is an organic fluorescent dye with a narrow bandwidth of light absorption between 260 nanometers and 900 nanometers and a narrow bandwidth of fluorescence between 260 nanometers and 1100 nanometers (“5- (and -6) -carboxytetramethylrhodamine-NHS ester” page 3 para. 3). Note that as evidenced by Vector Labs 5- (and -6) -carboxytetramethylrhodamine-NHS ester has a bandwidth of light absorption between 260 nanometers and 900 nanometers and a narrow bandwidth of fluorescence between 260 nanometers and 1100 nanometers (see absorption and emission spectra on page 3).
Regarding claim 18, Yamanaka teaches wherein: the fluorescent dyes has functional groups that can react with functional groups on a surface of inorganic nanoparticles (page 2 para. 7, “When a functional molecule and a silane coupling agent are covalently bonded, for example, N-hydroxysuccinimide (NHS) ester group, maleimide group, isocyanate group, isothiocyanate group, aldehyde group, paranitrophenyl group, di- A silane coupling agent having a functional molecule having an active group such as an ethoxymethyl group, an epoxy group, a cyano group and the like and a functional group (for example, an amino group, a hydroxyl group, a thiol group etc.) capable of reacting with these active groups be able to” page 3 para. 2).
Regarding claim 19, Yamanaka teaches wherein: the functional groups on the fluorescent dyes is at least one of a succinimidyl ester (“5- (and -6) -carboxytetramethylrhodamine-NHS ester…DY550-NHS ester… DY630-NHS ester” page 3 para. 3).
Regarding claim 20, Yamanaka teaches wherein: the functional groups on the fluorescent dyes are reactive functional groups (page 3 para. 3).
Regarding claim 21, Yamanaka teaches wherein: the fluorescent dyes react with functional groups on surface of inorganic nanoparticle by a condensation reaction (“by hydrolysis and condensation polymerization” page 3 para. 1).
Regarding claim 22, Yamanaka wherein: the plurality of first linker molecules with functional groups are an oligomer chain with two functional groups (“The linker molecule used in the present invention is not particularly limited as long as it has a maleimide group and an amino group in the molecule, but the maleimide group and the amino group may be a divalent aliphatic group or an arylene group or a combination thereof Preferably, they are linked molecules. The carbon number of the divalent aliphatic group is preferably an integer of 1 to 20, and more preferably an integer of 2 to 10” page 5 para. 3). Note that although Yamanaka fails to use the language “oligomer” the teaching of the divalent linker made of linked aliphatic groups of 1 to 20 carbons inherently provides an oligomer chain with two functional groups because the repeating aliphatic groups are reasonably interpreted as the oligomer.
Regarding claims 23-24, Yamanaka teaches wherein: a functional group R' and the functional group R" in the plurality of first linker molecules include one or more of an amino, a maleimide, wherein: a functional group R' and the functional group R" in the plurality of the first linker molecules are reactive functional groups (“The linker molecule used in the present invention is not particularly limited as long as it has a maleimide group and an amino group in the molecule” page 5 para. 3).
Regarding claims 25-26, Yamanaka teaches wherein: a backbone of the plurality of the first linker molecules are an alkyl chain, wherein: a number of repeated units in the plurality of the first linker molecules range from 20 to 1 (“divalent aliphatic group or an arylene group or a combination thereof Preferably, they are linked molecules. The carbon number of the divalent aliphatic group is preferably an integer of 1 to 20, and more preferably an integer of 2 to 10” page 5 para. 3).
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 1-3 and 6-22 and 25-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 91-112 of copending Application No. 19432869 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because copending Application No. 19432869 recites a method for producing conjugated inorganic nanoparticle fluorescent dye complexes for flow cytometry and biological applications (“A method for producing inorganic nanoparticle fluorescent dye complexes for flow cytometry and biological applications” claim 91), the method comprising: a) covering a surface of a plurality of inorganic nanoparticles with a functional group R using a coupling agent to form a plurality of functionalized inorganic nanoparticles (“the method comprising: a) hydrolyzing a functional coupling agent to cover reactive functional groups on a surface of a plurality of inorganic nanoparticles” claim 91); b) coupling fluorescent dyes to the plurality of functionalized inorganic nanoparticles to form a plurality of functionalized fluorescent inorganic nanoparticles (“b) reacting fluorescent dyes having functional groups with functionalized inorganic nanoparticles” claim 91); c) coupling a plurality of first linker molecules, attached to a functional group R", to the plurality of fluorescent functionalized inorganic nanoparticles (“c) reacting linker molecules or oligomers with functional groups on the surface of the plurality of inorganic nanoparticles firstly” claim 91, “The method of claim 91, wherein: the functional groups in linker molecules or oligomers include one or more of an amino, an alkylhalide, an azide, an alkyne, an aldehyde, a maleimide, a hydroxyl, an acetal,…” claim 109); and d) bioconjugating the plurality of fluorescent functionalized inorganic nanoparticles with antibodies or other bioactive molecules (“d) directly bio-conjugating functionalized fluorescent inorganic nanoparticles with antibodies or other bioactive molecules” claim 91).
Regarding claim 2, copending Application No. 19432869 further recites wherein using the coupling agent to cover the surface of the plurality of inorganic nanoparticles with functional groups further comprises, hydrolyzing the coupling agent (“hydrolyzing a functional coupling agent to cover reactive functional groups on a surface of a plurality of inorganic nanoparticles” claim 91).
Regarding claim 3, copending Application No. 19432869 further recites wherein coupling fluorescent dyes to the functionalized inorganic nanoparticles further comprises, mixing fluorescent dyes attached to the functional group R with functionalized inorganic nanoparticles (“reacting fluorescent dyes having functional groups with functionalized inorganic nanoparticles” claim 91, “wherein: the functional groups on the fluorescent dye is at least one of an amino, an alkylhalide, an azide…” para. 105).
Regarding claim 6, copending Application No. 19432869 further recites further comprising: reacting linker molecules or oligomers with a plurality of antibodies or other bioactive molecules to activate the plurality of antibodies or other bioactive molecules (“reacting linker molecules or oligomers with a plurality of antibodies or other bioactive molecules to activate the plurality of antibodies or other bioactive molecules” claim 92).
Regarding claim 7, copending Application No. 19432869 further recites further comprising: directly bio-conjugating functionalized fluorescent inorganic nanoparticles with activated antibodies or other bioactive molecules (claim 91).
Regarding claims 8-22, copending Application No. 19432869 further recites wherein: the plurality of inorganic nanoparticles are covered with an inorganic metal oxide; wherein: the plurality of inorganic nanoparticles include alumina nanoparticles, silica nanoparticles, titania nanoparticles, indium tin oxide nanoparticles, zinc oxide nanoparticles, iron oxide nanoparticles, antimony tin oxide nanoparticles, or nanoparticles covered with an inorganic metal oxide layer; wherein: a size of the plurality of inorganic nanoparticles is less than 500 nanometers, 200 nanometers, 100 nanometers, 50 nanometers, 25 nanometers, 15 nanometers, 10 nanometers, or 5 nanometers; wherein: the coupling agent is one of a silane coupling agent, a titanate coupling agent, an aluminate coupling agent, a zirconate coupling agent, a phosphate coupling agent, and a borate coupling agent; wherein: the functional group R on the coupling agent includes one or more of alkylhalide, azide, amino, alkyne, aldehyde, maleimide, hydroxyl, acetal, isocyanate, epoxide, acrylate, sulfonate (tosyl, mesyl), nitrophenyl carbonate, Biotins, folic acid, methacrylate, mercapto, tetrafluorophenyl esters, succinimidyl ester, pentafluorophenyl ester, hydrazides, vinyl, vinylsulfone, dibenzocyclooctyne group (DBCO), and methyltetrazine; wherein: the coupling agent comprises a silicon atom; and the plurality of first linker molecules that connect the functional group R" to the silicon atom includes one of an alkyl chain, a peptide chain, and a polyethylene oxide chain; wherein: a number of repeated units of the plurality of first linker molecules ranges from 5,000 to 1, from 3,000 to 1, from 2,000 to 1, from 1,000 to 1, from 500 to 1, from 100 to 1, or from 20 to 1; wherein: the fluorescent dyes is a fluorescent chemical compound that can emit light upon laser excitation; wherein: the fluorescent dyes is at least one of BODIPY derivatives, dipyrrin-metal derivatives, Atto derivatives, Cyanine derivatives, squaraine derivatives, Fluorescein derivatives, porphyrin, metalloporphyrin derivatives, phthalocyanine derivatives, Rhodamine derivatives, lanthanide complexes derivatives, and Pyrene dyes; wherein: the fluorescent dyes is an organic fluorescent dye with a narrow bandwidth of light absorption between 260 nanometers and 900 nanometers and a narrow bandwidth of fluorescence between 260 nanometers and 1100 nanometers; wherein: the fluorescent dyes has functional groups that can react with functional groups on a surface of inorganic nanoparticles; wherein: the functional groups on the fluorescent dyes is at least one of an amino, an alkylhalide, an azide, an alkyne, an aldehyde, a maleimide, a hydroxyl, an acetal, an isocyanate, an epoxide, an acrylate, a sulfonate (tosyl, mesyl), a nitrophenyl carbonate, a Biotins, a folic acid, a methacrylate, a mercapto, a tetrafluorophenyl ester, a succinimidyl ester, a pentafluorophenyl ester, a hydrazides, a vinyl, a vinylsulfone, a dibenzocyclooctyne group (DBCO), and a methyltetrazine and other reactive functional groups; wherein: the functional groups on the fluorescent dyes are reactive functional groups; wherein: the fluorescent dyes react with functional groups on surface of inorganic nanoparticle by a condensation reaction, a click chemistry reaction, a photochemistry reaction, a Suzuki coupling reaction, a Stille coupling reaction, a Sonogashira coupling reaction; or a Heck, Mcmurray and Knoevenagel, Wittig, Homer reaction; wherein: the plurality of first linker molecules with functional groups are an oligomer chain with one functional group, an oligomer chain with two functional groups, or branched oligomers with multi-functional groups (“wherein: the inorganic nanoparticles are metal oxide nanoparticles” claim 94, “wherein: the inorganic nanoparticles include alumina nanoparticles, silica nanoparticles, titania nanoparticles, indium tin oxide nanoparticles, zinc oxide nanoparticles, iron oxide nanoparticles, antimony tin oxide nanoparticles, or nanoparticles covered with an inorganic metal oxide layer” claim 95, “wherein: the size of the inorganic nanoparticles is less than 500 nanometers, 200 nanometers, 100 nanometers, 50 nanometers, 25 nanometers, 15nanometers, 10 nanometers, or 5 nanometers” claim 96, “wherein: the functional coupling agent is one of a silane coupling agent, a titanate coupling agent, an aluminate coupling agent, a zirconate coupling agent, a phosphate coupling agent, and a borate coupling agent” claim 97, “wherein: the functional organic groups on the functional coupling agents include one or more of alkylhalide, azide, amino, alkyne, aldehyde, maleimide, hydroxyl, acetal, isocyanate, epoxide, acrylate, sulfonate (tosyl, mesyl), nitrophenyl carbonate, Biotins, folic acid, methacrylate, mercapto, tetrafluorophenyl esters, succinimidyl ester, pentafluorophenyl ester, hydrazides, vinyl, vinylsulfone, dibenzocyclooctyne group (DBCO), and methyltetrazine” claim 98, “wherein: the linker that connects the functional groups to a silicon atom includes one of an alkyl chain, a peptide chain, and a polyethylene oxide chain” claim 99, “wherein: the number of repeated units of the linker ranges from 5,000 to 1, from 3,000 to 1, from 2,000 to 1, from 1,000 to 1, from 500 to 1, from 100 to 1, or from 20 to 1” claim 100, “wherein: the fluorescent dye is a fluorescent chemical compound that can emit light upon laser excitation” claim 101, “wherein: the fluorescent dye is at least one of BODIPY derivatives, dipyrrin-metal derivatives, Atto derivatives, Cyanine derivatives, squaraine derivatives, Fluorescein derivatives, porphyrin, metalloporphyrin derivatives, phthalocyanine derivatives, Rhodamine derivatives, lanthanide complexes derivatives, and Pyrene dyes” claim 102, “wherein: the fluorescent dye is an organic fluorescent dye with a narrow bandwidth of light absorption between 260 nanometers and 900 nanometers and a narrow bandwidth of fluorescence between 260 nanometers and 1100 nanometers” claim 103, “wherein: the fluorescent dye has functional groups that can react with functional groups on a surface of inorganic nanoparticles” claim 104, “wherein: the functional groups on the fluorescent dye is at least one of an amino, an alkylhalide, an azide, an alkyne, an aldehyde, a maleimide, a hydroxyl, an acetal, an isocyanate, an epoxide, an acrylate, a sulfonate (tosyl, mesyl), a nitrophenyl carbonate, a Biotins, a folic acid, a methacrylate, a mercapto, a tetrafluorophenyl ester, a succinimidyl ester, a pentafluorophenyl ester, a hydrazides, a vinyl, a vinylsulfone, a dibenzocyclooctyne group (DBCO), and a methyltetrazine and other reactive functional organic groups” claim 105, “wherein: the functional groups on the fluorescent dye are reactive functional organic groups” claim 106, “wherein: the fluorescent dyes react with functional groups on surface of inorganic nanoparticle by a condensation reaction, a click chemistry reaction, a photochemistry reaction, a Suzuki coupling reaction, a Stille coupling reaction, a Sonogashira coupling reaction; or a Heck, Mcmurray and Knoevenagel, Wittig, Horner reaction” claim 107, “wherein: the linker molecules or oligomers with functional groups are an oligomer chain with one functional group, an oligomer chain with two functional groups, or branched oligomers with multi-functional groups” claim 108).
Regarding claims 25-26, copending Application No. 19432869 further recites wherein: a backbone of the plurality of the first linker molecules are one of an alkyl chain, a peptide chain, and a polyethylene oxide chain; wherein: a number of repeated units in the plurality of the first linker molecules range from 10,000 to 1, from 5,000 to 1, from 3,000 to 1, from 2,000 to 1, from 1,000 to 1, from 500 to 1, from 100 to 1, or from 20 to 1 (“wherein: the backbone of the linker molecules are one of an alkyl chain, a peptide chain, and a polyethylene oxide chain” claim 111, “wherein: the number of repeated units in the linker molecules range from 10,000 to 1, from 5,000 to 1, from 3,000 to 1, from 2,000 to 1, from 1,000 to 1, from 500 to 1, from 100 to 1, or from 20 to 1” claim 112).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 4-5 and 23-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 91-112 of copending Application No. 19432869 in view of Yamanaka et al. (JP 2014153057 A) (“Yamanaka”).
Regarding claims 4-5 and 23-24, copending Application No. 19432869 recites the method of claim 1 as discussed above.
Copending Application No. 19432869 fails to recite wherein coupling a plurality of first linker molecules to the surface of the plurality of functionalized inorganic nanoparticles further comprises, mixing the plurality of first linker molecules, attached to a functional group R' and a functional group R", with the functionalized inorganic nanoparticles, wherein the functional group R' reacts with the functional group R covering the surface of a plurality of inorganic nanoparticles; changing the functional group R", attached to the plurality of first linker molecules, to a functional group R2, by mixing a plurality of second linker molecules to the fluorescent functionalized inorganic nanoparticles, wherein a functional group of the plurality of second linker molecules reacts with the functional group R" of the plurality of first linker molecules to form the functional group R2; wherein: a functional group R' and the functional group R" in the plurality of first linker molecules include one or more of an amino, an alkylhalide, an azide, an alkyne, an aldehyde, a maleimide, a hydroxyl, an acetal, an isocyanate, an epoxide, an acrylate, a sulfonate (tosyl, mesyl), a nitrophenyl carbonate, a Biotins, a folic acid, a methacrylate, a mercapto, a tetrafluorophenyl ester, a succinimidyl ester, a pentafluorophenyl ester, a hydrazides, a vinyl, a vinylsulfone, a dibenzocyclooctyne group (DBCO), an a methyltetrazine; wherein: a functional group R' and the functional group R" in the plurality of the first linker molecules are reactive functional groups.
Yamanaka teaches a “method of manufacturing labeled antibody” (Title). Yamanaka further teaches wherein coupling a plurality of first linker molecules to the surface of the plurality of functionalized inorganic nanoparticles further comprises, mixing the plurality of first linker molecules, attached to a functional group R' and a functional group R", with the functionalized inorganic nanoparticles, wherein the functional group R' reacts with the functional group R covering the surface of a plurality of inorganic nanoparticles (page 5 paras. 3-5). Note that although Yamanaka fails to use the language “mixing”, the teaching of reacting the linker molecule with the particle in a buffer solution or a solvent such that the nanoparticles are dispersed and at temperatures of 60 degrees Celsius for 120 minutes inherently provides a step of mixing because these experimental conditions effectively cause the mixing of the two reagents. Yamanaka further teaches further comprises, changing the functional group R", attached to the plurality of first linker molecules, to a functional group R2, by mixing a plurality of second linker molecules to the fluorescent functionalized inorganic nanoparticles, wherein a functional group of the plurality of second linker molecules reacts with the functional group R" of the plurality of first linker molecules to form the functional group R2 (page 5 para. 6). Note that although Yamanaka fails to use the language “second linker molecule” the teaching of changing the amino group of the linker with a carbodiimide to produce a carboxyl group inherently provides the use of a second linker molecule to change R" to R2. Yamanaka teaches wherein: a functional group R' and the functional group R" in the plurality of first linker molecules include one or more of an amino, a maleimide; wherein: a functional group R' and the functional group R" in the plurality of the first linker molecules are reactive functional groups (page 5 para. 3). Yamanaka further suggests that using said linker enables great suppression of nonspecific adsorption and effective targeting of antigens (“And, if the labeled antibody in the form in which the carboxyl group of the antibody and the thiol group on the surface of the silica nanoparticle are linked via the linker molecule is used for immunoassay, nonspecific adsorption is greatly suppressed and the capture ability of the target antigen is also achieved” page 1 para. 4).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of copending Application No. 19432869 to rely on wherein coupling a plurality of first linker molecules to the surface of the plurality of functionalized inorganic nanoparticles further comprises, mixing the plurality of first linker molecules, attached to a functional group R' and a functional group R", with the functionalized inorganic nanoparticles; wherein the functional group R' reacts with the functional group R covering the surface of a plurality of inorganic nanoparticles; changing the functional group R", attached to the plurality of first linker molecules, to a functional group R2, by mixing a plurality of second linker molecules to the fluorescent functionalized inorganic nanoparticles, wherein a functional group of the plurality of second linker molecules reacts with the functional group R" of the plurality of first linker molecules to form the functional group R2; wherein: a functional group R' and the functional group R" in the plurality of first linker molecules include one or more of an amino, and a maleimide; wherein: a functional group R' and the functional group R" in the plurality of the first linker molecules are reactive functional groups taught by Yamanaka because Yamanaka suggests that this enables great suppression of nonspecific adsorption and effective targeting of antigens, and copending Application No. 19432869 is concerned with antibody conjugates for flow cytometry and biological applications. A person having ordinary skill in the art would have had a reasonable expectation of success because both copending Application No. 19432869 and Yamanaka teach a method for producing conjugated inorganic nanoparticle fluorescent dye complexes for flow cytometry and biological applications, the method comprising: a) covering a surface of a plurality of inorganic nanoparticles with a functional group R using a coupling agent to form a plurality of functionalized inorganic nanoparticles; b) coupling fluorescent dyes to the plurality of functionalized inorganic nanoparticles to form a plurality of functionalized fluorescent inorganic nanoparticles; c) coupling a plurality of first linker molecules, attached to a functional group R", to the plurality of fluorescent functionalized inorganic nanoparticles; and d) bioconjugating the plurality of fluorescent functionalized inorganic nanoparticles with antibodies or other bioactive molecules.
This is a provisional nonstatutory double patenting rejection.
Conclusion
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/Fernando Ivich/ Examiner, Art Unit 1678
/GREGORY S EMCH/ Supervisory Patent Examiner, Art Unit 1678
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