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 .
Election/Restrictions
Applicant’s election without traverse of Group I (Claims 1-7), drawn to a nanoparticle comprising a core comprising a first fluorophore which is a semiconductor, the core coated with a first layer comprising a second fluorophore, wherein the emission and/or excitation wavelength of the first fluorophore is different from the emission and/or excitation wavelength of the second fluorophore, in the reply filed on 07/24/2026 is acknowledged.
Note, Applicant elects Group I without traverse, asserts that claim 1 is allowable and requests the rejoinder of claims 9-14 of Group II invention on Pg. 7 of the response filed 07/24/2026. As elected Group I (Claims 1-7) is currently rejected as documented below in this Non-final office action, claims 9-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected Group II, drawn to a method for multiplexed detection of a plurality of target biomolecules using a plurality of nanoparticles, and Group III, drawn to drawn to a kit-of-parts, there being no allowable generic or linking claim. The request for rejoinder of claims 9-14 of Group II invention directed to a method of using the nanoparticle of claim 1 will be considered when the nanoparticle of claim 1 becomes allowable.
Claims Status
Claims 1-7 and 9-16 are pending.
Claims 9-16 are withdrawn.
Claims 8 are canceled.
Claims 1-7 are currently under examination
Priority
This application is a U.S. National Phase Application of International Application No. PCT/EP2022/077835, filed October 6, 2022, which claims the benefit of U.S. Provisional Application No. 63/252,744, filed October 6, 2021. Accordingly, the priority date of the instant claim set is determined to be October 6, 2021.
Specification
The following guidelines illustrate the preferred layout for the specification of a utility application. These guidelines are suggested for the applicant’s use.
Arrangement of the Specification
As provided in 37 CFR 1.77(b), the specification of a utility application should include the following sections in order. Each of the lettered items should appear in upper case, without underlining or bold type, as a section heading. If no text follows the section heading, the phrase “Not Applicable” should follow the section heading:
(a) TITLE OF THE INVENTION.
(b) CROSS-REFERENCE TO RELATED APPLICATIONS.
(c) STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT.
(d) THE NAMES OF THE PARTIES TO A JOINT RESEARCH AGREEMENT.
(e) INCORPORATION-BY-REFERENCE OF MATERIAL SUBMITTED ON A READ-ONLY OPTICAL DISC, AS A TEXT FILE OR AN XML FILE VIA THE PATENT ELECTRONIC SYSTEM.
(f) STATEMENT REGARDING PRIOR DISCLOSURES BY THE INVENTOR OR A JOINT INVENTOR.
(g) BACKGROUND OF THE INVENTION.
(1) Field of the Invention.
(2) Description of Related Art including information disclosed under 37 CFR 1.97 and 1.98.
(h) BRIEF SUMMARY OF THE INVENTION.
(i) BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S).
(j) DETAILED DESCRIPTION OF THE INVENTION.
(k) CLAIM OR CLAIMS (commencing on a separate sheet).
(l) ABSTRACT OF THE DISCLOSURE (commencing on a separate sheet).
(m) SEQUENCE LISTING. (See MPEP § 2422.03 and 37 CFR 1.821 - 1.825). A “Sequence Listing” is required on paper if the application discloses a nucleotide or amino acid sequence as defined in 37 CFR 1.821(a) and if the required “Sequence Listing” is not submitted as an electronic document either on read-only optical disc or as a text file via the patent electronic system.
Content of Specification
(a) TITLE OF THE INVENTION: See 37 CFR 1.72(a) and MPEP § 606. The title of the invention should be placed at the top of the first page of the specification unless the title is provided in an application data sheet. The title of the invention should be brief but technically accurate and descriptive, preferably from two to seven words. It may not contain more than 500 characters.
(b) CROSS-REFERENCES TO RELATED APPLICATIONS: See 37 CFR 1.78 and MPEP § 211 et seq.
(c) STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT: See MPEP § 310.
(d) THE NAMES OF THE PARTIES TO A JOINT RESEARCH AGREEMENT. See 37 CFR 1.71(g).
(e) INCORPORATION-BY-REFERENCE OF MATERIAL SUBMITTED ON A READ-ONLY OPTICAL DISC, AS A TEXT FILE OR AN XML FILE VIA THE PATENT ELECTRONIC SYSTEM: The specification is required to include an incorporation-by-reference of electronic documents that are to become part of the permanent United States Patent and Trademark Office records in the file of a patent application. See 37 CFR 1.77(b)(5) and MPEP § 608.05. See also the Legal Framework for Patent Electronic System posted on the USPTO website (https://www.uspto.gov/sites/default/files/documents/2019LegalFrameworkPES.pdf) and MPEP § 502.05
(f) STATEMENT REGARDING PRIOR DISCLOSURES BY THE INVENTOR OR A JOINT INVENTOR. See 35 U.S.C. 102(b) and 37 CFR 1.77.
(g) BACKGROUND OF THE INVENTION: See MPEP § 608.01(c). The specification should set forth the Background of the Invention in two parts:
(1) Field of the Invention: A statement of the field of art to which the invention pertains. This statement may include a paraphrasing of the applicable U.S. patent classification definitions of the subject matter of the claimed invention. This item may also be titled “Technical Field.”
(2) Description of the Related Art including information disclosed under 37 CFR 1.97 and 37 CFR 1.98: A description of the related art known to the applicant and including, if applicable, references to specific related art and problems involved in the prior art which are solved by the applicant’s invention. This item may also be titled “Background Art.”
(h) BRIEF SUMMARY OF THE INVENTION: See MPEP § 608.01(d). A brief summary or general statement of the invention as set forth in 37 CFR 1.73. The summary is separate and distinct from the abstract and is directed toward the invention rather than the disclosure as a whole. The summary may point out the advantages of the invention or how it solves problems previously existent in the prior art (and preferably indicated in the Background of the Invention). In chemical cases it should point out in general terms the utility of the invention. If possible, the nature and gist of the invention or the inventive concept should be set forth. Objects of the invention should be treated briefly and only to the extent that they contribute to an understanding of the invention.
(i) BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S): See MPEP § 608.01(f). A reference to and brief description of the drawing(s) as set forth in 37 CFR 1.74.
(j) DETAILED DESCRIPTION OF THE INVENTION: See MPEP § 608.01(g). A description of the preferred embodiment(s) of the invention as required in 37 CFR 1.71. The description should be as short and specific as is necessary to describe the invention adequately and accurately. Where elements or groups of elements, compounds, and processes, which are conventional and generally widely known in the field of the invention described, and their exact nature or type is not necessary for an understanding and use of the invention by a person skilled in the art, they should not be described in detail. However, where particularly complicated subject matter is involved or where the elements, compounds, or processes may not be commonly or widely known in the field, the specification should refer to another patent or readily available publication which adequately describes the subject matter.
(k) CLAIM OR CLAIMS: See 37 CFR 1.75 and MPEP § 608.01(m). The claim or claims must commence on a separate sheet or electronic page (37 CFR 1.52(b)(3)). Where a claim sets forth a plurality of elements or steps, each element or step of the claim should be separated by a line indentation. There may be plural indentations to further segregate subcombinations or related steps. See 37 CFR 1.75 and MPEP 608.01(i) - (p).
(l) ABSTRACT OF THE DISCLOSURE: See 37 CFR 1.72 (b) and MPEP § 608.01(b). The abstract is a brief narrative of the disclosure as a whole, as concise as the disclosure permits, in a single paragraph preferably not exceeding 150 words, commencing on a separate sheet following the claims. In an international application which has entered the national stage (37 CFR 1.491(b)), the applicant need not submit an abstract commencing on a separate sheet if an abstract was published with the international application under PCT Article 21. The abstract that appears on the cover page of the pamphlet published by the International Bureau (IB) of the World Intellectual Property Organization (WIPO) is the abstract that will be used by the USPTO. See MPEP § 1893.03(e).
(m) SEQUENCE LISTING: See 37 CFR 1.821 - 1.825 and MPEP §§ 2421 - 2431. The requirement for a sequence listing applies to all sequences disclosed in a given application, whether the sequences are claimed or not. See MPEP § 2422.01.
The disclosure is objected to because of the following informalities:
Order of sections
Required sections
Section subheadings.
Appropriate correction is required.
Claim Objections
Claim 1-7 are objected to because of the following informalities:
“A nanoparticle which comprises;” (Claim 1) Claims are clearer and more concise when the preamble sets forth the intended outcome of the claim.
Each claim should have only one period “.” , which is at the end of the claim. See MPEP 608.01(m) Forms of Claim1 [R-10.2019]. The periods included in limitations “a.” (ln 2) and “b.” (ln 3) in claim 1 and “a.” (ln 3), “b.” (ln 4) and “c.” (ln 5) in claim 6 should be deleted and replaced with single or double parentheses around the character (e.g., “a)” or “(a)”).
“is different to the emission” (ln 5-6) should be amended to “is different from the emission”. (Claim 1) Claims 2-7 depend on claim 1.
“which is a semiconductor” (ln 2) should be amended to wherein clause once indefiniteness is resolved as discussed below in the 35 U.S.C. 112 section. (Claim 1) Claims 2-7 depend on claim 1.
“which core is coated with a first layer” (ln 3) should be amended to wherein clause once indefiniteness is resolved as discussed below in the 35 U.S.C. 112 section. (Claim 1) Claims 2-7 depend on claim 1.
“wherein,” (ln 5) should be amended to “wherein” to remove the comma. (Claim 1) Claims 2-7 depend on claim 1.
“and/or” (ln 3) should be removed. (Claim 6)
“and” (ln 6) should be removed. (Claim 4)
“nanoparticles have” should be amended to “wherein the nanoparticle has”(ln 1) (Claim 7)
Appropriate correction is required.
Claim Rejections - 35 USC § 112 (b)
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 1-7 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 is indefinite over the limitation “a core comprising a first fluorophore, which is a semiconductor”(ln 2). The specification teaches “The nanoparticle of the first aspect of the invention is referred to herein as a core-layer nanoparticle, that is to say that the nanoparticle comprises a central core, for example a single core, of one material being a semiconductor with a layer, or multiple layers, that surround the core, wherein the core and surrounding layers differ either physically (for ex- ample in atomic structure) or chemically (for example in the materials that they are com- posed of)” (Pg. 3 ln 10-15). It is unclear whether the core or first fluorophore is considered the semiconductor or whether both are considered the semiconductor. Claims 2-7 depend on claim 1.
Claim 1 is indefinite over the limitation “a core comprising a first fluorophore, which is a semiconductor; and b. which core is coated with a first layer” (ln 2-3). The specification teaches “The nanoparticle of the first aspect of the invention is referred to herein as a core-layer nanoparticle, that is to say that the nanoparticle comprises a central core, for example a single core, of one material being a semiconductor with a layer, or multiple layers, that surround the core, wherein the core and surrounding layers differ either physically (for ex- ample in atomic structure) or chemically (for example in the materials that they are com- posed of)” (Pg. 3 ln 10-15). It is unclear whether the first fluorophore or semiconductor is considered the core or both are considered the core. Claims 2-7 depend on claim 1.
Claim 7 is indefinite over the limitation “nanoparticles have an average diameter of less than about 300 nm”. The phrase “less than about" is vague and indefinite based on the unclear metes and bounds meant by the phrase. The phrase "less than” typically indicates a maximum point. The phrase "less than", however, is controverted by the term "about" which implies that values above and below are permitted. In Amgen, Inc. v. Chugai Pharmaceutical Co., 927 F.2d.1200 (CAFC 1991), the CAFC stated, "The district court held claims 4 and 6 of the patent invalid because their specific activity limitation of "at least about 160,000" was indefinite". After review, the CAFC states "We therefore affirm the district court's determination on this issue." Thus, the phrase "less than about" is indefinite where the metes and bounds of the term were not defined in the specification because it is not clear if “less than about” 300 nm would include a diameter that is about 300 nm (e.g., 350 nm), because it is not clear if 350 nm would be less than 300 nm.
Claim Rejections - 35 USC § 112 (d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 3 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 3 recites the limitation “wherein the first fluorophore is selected from the list consisting of quantum dots, rods, semiconductor quantum dots, perovskite quantum dots, quantum rods, Pdots and silicon quantum dots, or mixtures thereof” (Claim 3 ln 1-4) whereas claim 1 recites the limitation “a first fluorophore, which is a semiconductor” (Claim 1 ln 2). Claim 3 does not further limit claim 1, rather claim 3 broaden the limitation “a first fluorophore, which is a semiconductor” recited in claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Notes: As elaborated below, claims 1-7 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Oldenburg et al. (“Oldenburg”; Patent App. Pub. WO 2015054493 A1, April 16, 2015.
Claim Rejections - 35 USC § 102
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.
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 1-7 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Oldenburg et al. (“Oldenburg”; Patent App. Pub. WO 2015054493 A1, April 16, 2015.
Claim interpretations: Regarding claim 1, the core and first fluorophore are interpreted as a semiconductor. Thus, the first fluorophore is considered the semiconductor which is interpreted as the core. Regarding claim 3, first fluorophore is interpreted as semiconductor that is interpreted as a quantum dot. Regarding claim 4, The limitation(s) reciting “optionally” is interpreted as rendering the phrase thereafter as an optional limitation to the claim. Regarding claim 7, "nanoparticles have an average diameter of less than about 300 nm" is interpreted as a nanoparticle with an average diameter less than 300 nm.
Oldenburg discloses “The disclosed technology relates generally to material systems which include a plurality of particles and methods of making the same. The particles have a core and a shell which encapsulates the core and has at least one atomic element not included in the core. The cores of the particles have a median maximum dimension that is less than 10 microns and a median of at least one axial dimension that is between 10 nm and 500 nm. The shells of the particles have a median thickness that is less than 100 nm, a silicon concentration that is between 10% and 50% on the basis of the weight of the shells, and an aluminum concentration that is between 0.01 % and 5% on the basis of the weight of the shells.” (Abstract).
Regarding claim 1, Oldenburg teaches a nanoparticle wherein “the nanoparticles are quantum dot nanoparticles comprising a semiconductor material” (Para.17). Oldenburg teaches a nanoparticle wherein “the nanoparticles have a core-shell structure, wherein the nanoparticles have a nanoparticle core comprising the semiconductor material and a nanoparticle shell comprising a material different from the nanoparticle core material” (Para. 18). Oldenburg teaches a nanoparticle wherein “at least one of the core or the shell includes a light- emitting center incorporated therein, wherein the light-emitting center is selected from the group consisting of fluorophore, dye, luminophore, a chemiluminescent species and phosphor” (Para. 32) and “light emitting entities (LEEs) are incorporated within the core, within one or more shells or bound to the surface of the core or shells. LEEs include fluorophores, dyes, luminophores, chemiluminescent species, or phosphors.” (Para. 112). Oldenburg teaches a nanoparticle wherein “Preferably, the band gap energy of the over coating is greater than that of the core. When illuminated with light of a wavelength that is absorbed by the quantum dots, the quantum dots emit light with a peak wavelength 10 or more nanometers greater than that of the incident light.” (Para.107). Thus, Oldenburg teaches a nanoparticle which comprises; a. a core comprising a first fluorophore, which is a semiconductor; and b. which core is coated with a first layer, wherein the first layer comprises a second fluorophore; wherein, the emission and/or excitation wavelength of the first fluorophore is different to the emission and/excitation wavelength of the second fluorophore
Regarding claim 2, Oldenburg teaches a nanoparticle wherein “light emitting entities (LEEs) are incorporated … within one or more shells or bound to the surface of the core or shells. LEEs include fluorophores, dyes, luminophores, chemiluminescent species, or phosphors.” (Para. 112). Thus, Oldenburg teaches a nanoparticle wherein the second fluorophore is embedded within a matrix provided by the first layer.
Regarding claim 3, Oldenburg teaches a nanoparticle wherein “the nanoparticles are quantum dot nanoparticles comprising a semiconductor material selected from the group consisting of Si, Ge, CdS, CdSe, CdTe, ZnS, ZnSe, ZnTe, GaAs, GaP, GaAs, GaSb, HgS, HgSe, HgTe, InAs, InP, InSb, AlAs, AlP, and AlSb, wherein the quantum dot nanoparticles emit light having a peak wavelength” (Para. 17). Oldenburg teaches a nanoparticle wherein “a nanoparticle core comprising the semiconductor material and a nanoparticle shell comprising a material different from the nanoparticle core material” (Para. 18). Thus, Oldenburg teaches a nanoparticle wherein the first fluorophore is selected from the list consisting of quantum dots, rods, semiconductor quantum dots, perovskite quantum dots, quantum rods, Pdots and silicon quantum dots, or mixtures thereof.
Regarding claim 4, Oldenburg teaches a nanoparticle wherein “the LEEs are organic fluorescent dyes that emit light in the visible to near infrared light of wavelength in the range of 400 to 900 nm when excited by ultraviolet to near infrared light of wavelength in the range of 200 to 700 nm. The organic fluorescent dyes include fluorescein type dye molecules, rhodamine type dye molecules, Alexa Fluor (produced by Invitrogen Corp.) type dye molecules, BODIPY (produced by Invitrogen Corp.) type dye molecules … coumarin type dye molecules…Texas Red type dye molecules, cyanine type dye molecules, and the like. Specific examples of the organic fluorescent dye include 5- carboxy-fluorescein, 6-carboxy-fluorescein, 5,6-dicarboxy-fluorescein, 6-carboxy- 2',4,4',5',7,7'-hexachlorofluorescein, 6-carboxy-2',4,7,7'-tetrachlorofluorescein, 6- carboxy-4',5'-dichloro-2',7'-dimethoxyfluorescein, naphthofluorescein, 5-carboxy- rhodamine, 6-carboxy-rhodamine, 5,6-dicarboxy-rhodamine, rhodamine 6G, tetramethyl rhodamine, X-rhodamine, and … Alexa Fluor 405… Alexa Fluor 488… Alexa Fluor 546…Alexa Fluor 647… Alexa Fluor 680, Alexa Fluor 700, Alexa Fluor 750, BODIPY FL, BODIPY TMR, BODIPY 493/503, BODIPY 530/550, BODIPY 558/568, BODIPY 564/570, BODIPY 576/589, BODIPY 581/591 , BODIPY 630/650, BODIPY 650/665 (the above produced by Invitrogen Corp.), methoxycoumarin,… Cy 5, Cy 5.5, Cy 7, or the like.” (Para. 112). Thus, Oldenburg teaches a nanoparticle wherein the second fluorophore is an organic fluorophore, optionally wherein the organic fluorophore is selected from the list consisting of Atto 425, Alexa fluor 405, Alexa Fluor 488, fluoresceine, DiO, Atto 488, BODIPY FL, Cy3, DiI, Alexa fluor 546, Atto 550, BODIPY TMR-X, Cy5, Alexa fluor 647, Texas red, DiD, Atto647(N), Atto 655, Cy7, Alexa fluor 680, Alexa fluor 750, Atto 680, and Atto 700, BODIPY, Brilliant Violet, Cyanine, Alexa, Atto, fluorescein, coumarin, rhodamine, xanthene fluorophore families and derivatives and combinations thereof.
Regarding claim 5, Oldenburg teaches a nanoparticle wherein “one or both of the shell and the intermediate shell comprises a metal or an inorganic metal oxide.” (Para. 23). Oldenburg teaches a nanoparticle wherein “the shell material is a polymer, metal, or metal oxide” (Para. 120) Thus, Oldenburg teaches a nanoparticle wherein the nanoparticle comprises an outer layer, wherein the outer layer comprises a metal, an inorganic oxide or a polymer.
Regarding claim 6, Oldenburg teaches a nanoparticle wherein “a bifunctional linker molecule or a biomolecule attached to a surface of each particle… a molecule selected from the group consisting of a protein, antibody, DNA, RNA and combinations thereof, wherein the molecule is bonded to a particle surface.” (Para. 26-27). Oldenburg also teaches a nanoparticle wherein “the nanoparticle may be further functionalized with a targeting moiety… The targeting moiety may include, but is not limited to, antibodies and fragments thereof, haptens, polypeptides, oligonucleotides, DNA, anti- sense RNA, peptide nucleic acids, proteins, chimeric and/or fusion proteins, and the like”(Para. 130) and “The targeting moiety may be attached to the surface of the coated nanoparticle via a linker” (Para. 131). “Direct linking of the targeting moiety implies only that functional groups on the coating surface of the particle and the targeting moiety itself serve as the points of chemical attachment” (Para. 132). Thus, Oldenburg teaches a nanoparticle wherein the nanoparticle comprises a coating, wherein the coating comprises: a. a repulsive component; and/or b. a linker; and/or c. a detection probe.
Regarding claim 7, Oldenburg teaches a nanoparticle wherein “the nanoparticles have a median maximum dimension that is less than 100 nm” (Para. 13). Thus, Oldenburg teaches nanoparticles have an average diameter of less than about 300 nm.
Claim Rejections - 35 USC § 103
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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-7 are rejected under 35 U.S.C. 103 as being unpatentable over Oldenburg et al. (“Oldenburg”; Patent App. Pub. WO 2015054493 A1, April 16, 2015.
Claim interpretations: Regarding claim 1, the core and first fluorophore are interpreted as a semiconductor. Thus, the first fluorophore is considered the semiconductor which is interpreted as the core. Regarding claim 3, first fluorophore is interpreted as semiconductor that is interpreted as a quantum dot. Regarding claim 4, The limitation(s) reciting “optionally” is interpreted as rendering the phrase thereafter as an optional limitation to the claim. Regarding claim 7, "nanoparticles have an average diameter of less than about 300 nm" is interpreted as a nanoparticle with an average diameter less than 300 nm.
Oldenburg discloses “The disclosed technology relates generally to material systems which include a plurality of particles and methods of making the same. The particles have a core and a shell which encapsulates the core and has at least one atomic element not included in the core. The cores of the particles have a median maximum dimension that is less than 10 microns and a median of at least one axial dimension that is between 10 nm and 500 nm. The shells of the particles have a median thickness that is less than 100 nm, a silicon concentration that is between 10% and 50% on the basis of the weight of the shells, and an aluminum concentration that is between 0.01 % and 5% on the basis of the weight of the shells.” (Abstract).
Regarding claim 1, Oldenburg teaches a nanoparticle wherein “the nanoparticles are quantum dot nanoparticles comprising a semiconductor material” (Para.17). Oldenburg teaches a nanoparticle wherein “the nanoparticles have a core-shell structure, wherein the nanoparticles have a nanoparticle core comprising the semiconductor material and a nanoparticle shell comprising a material different from the nanoparticle core material” (Para. 18). Oldenburg teaches a nanoparticle wherein “at least one of the core or the shell includes a light- emitting center incorporated therein, wherein the light-emitting center is selected from the group consisting of fluorophore, dye, luminophore, a chemiluminescent species and phosphor” (Para. 32) and “light emitting entities (LEEs) are incorporated within the core, within one or more shells or bound to the surface of the core or shells. LEEs include fluorophores, dyes, luminophores, chemiluminescent species, or phosphors.” (Para. 112). Oldenburg teaches a nanoparticle wherein “Preferably, the band gap energy of the over coating is greater than that of the core. When illuminated with light of a wavelength that is absorbed by the quantum dots, the quantum dots emit light with a peak wavelength 10 or more nanometers greater than that of the incident light.” (Para.107). Thus, Oldenburg teaches a nanoparticle which comprises; a. a core comprising a first fluorophore, which is a semiconductor; and b. which core is coated with a first layer, wherein the first layer comprises a second fluorophore; wherein, the emission and/or excitation wavelength of the first fluorophore is different to the emission and/excitation wavelength of the second fluorophore
Therefore, the invention as recited in claim 1 is prima facie obvious over the prior art Oldenburg et al. One of ordinary skill in the art would have had a reasonable expectation of success given the obviousness of the claim limitations based on the interpretation of the claims. These claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome according to the limitations of claim 1. It would have been obvious to provide a nanoparticle which comprises; a. a core comprising a first fluorophore, which is a semiconductor; and b. which core is coated with a first layer, wherein the first layer comprises a second fluorophore; wherein, the emission and/or excitation wavelength of the first fluorophore is different to the emission and/excitation wavelength of the second fluorophore according to the limitations of the instant application claim 1 based on Oldenburg et al. (Patent App. Pub. No. WO 2015054493 A1). Doing so would allow for stable shell surface for long term encapsulation of fluorescent, magnetic, and/or optically responsive molecules and nanoparticles.
Regarding claim 2, Oldenburg teaches a nanoparticle wherein “light emitting entities (LEEs) are incorporated … within one or more shells or bound to the surface of the core or shells. LEEs include fluorophores, dyes, luminophores, chemiluminescent species, or phosphors.” (Para. 112). Thus, Oldenburg teaches a nanoparticle wherein the second fluorophore is embedded within a matrix provided by the first layer.
Regarding claim 3, Oldenburg teaches a nanoparticle wherein “the nanoparticles are quantum dot nanoparticles comprising a semiconductor material selected from the group consisting of Si, Ge, CdS, CdSe, CdTe, ZnS, ZnSe, ZnTe, GaAs, GaP, GaAs, GaSb, HgS, HgSe, HgTe, InAs, InP, InSb, AlAs, AlP, and AlSb, wherein the quantum dot nanoparticles emit light having a peak wavelength” (Para. 17). Oldenburg teaches a nanoparticle wherein “a nanoparticle core comprising the semiconductor material and a nanoparticle shell comprising a material different from the nanoparticle core material” (Para. 18). Thus, Oldenburg teaches a nanoparticle wherein the first fluorophore is selected from the list consisting of quantum dots, rods, semiconductor quantum dots, perovskite quantum dots, quantum rods, Pdots and silicon quantum dots, or mixtures thereof.
Regarding claim 4, Oldenburg teaches a nanoparticle wherein “the LEEs are organic fluorescent dyes that emit light in the visible to near infrared light of wavelength in the range of 400 to 900 nm when excited by ultraviolet to near infrared light of wavelength in the range of 200 to 700 nm. The organic fluorescent dyes include fluorescein type dye molecules, rhodamine type dye molecules, Alexa Fluor (produced by Invitrogen Corp.) type dye molecules, BODIPY (produced by Invitrogen Corp.) type dye molecules … coumarin type dye molecules…Texas Red type dye molecules, cyanine type dye molecules, and the like. Specific examples of the organic fluorescent dye include 5- carboxy-fluorescein, 6-carboxy-fluorescein, 5,6-dicarboxy-fluorescein, 6-carboxy- 2',4,4',5',7,7'-hexachlorofluorescein, 6-carboxy-2',4,7,7'-tetrachlorofluorescein, 6- carboxy-4',5'-dichloro-2',7'-dimethoxyfluorescein, naphthofluorescein, 5-carboxy- rhodamine, 6-carboxy-rhodamine, 5,6-dicarboxy-rhodamine, rhodamine 6G, tetramethyl rhodamine, X-rhodamine, and … Alexa Fluor 405… Alexa Fluor 488… Alexa Fluor 546…Alexa Fluor 647… Alexa Fluor 680, Alexa Fluor 700, Alexa Fluor 750, BODIPY FL, BODIPY TMR, BODIPY 493/503, BODIPY 530/550, BODIPY 558/568, BODIPY 564/570, BODIPY 576/589, BODIPY 581/591 , BODIPY 630/650, BODIPY 650/665 (the above produced by Invitrogen Corp.), methoxycoumarin,… Cy 5, Cy 5.5, Cy 7, or the like.” (Para. 112). Thus, Oldenburg teaches a nanoparticle wherein the second fluorophore is an organic fluorophore, optionally wherein the organic fluorophore is selected from the list consisting of Atto 425, Alexa fluor 405, Alexa Fluor 488, fluoresceine, DiO, Atto 488, BODIPY FL, Cy3, DiI, Alexa fluor 546, Atto 550, BODIPY TMR-X, Cy5, Alexa fluor 647, Texas red, DiD, Atto647(N), Atto 655, Cy7, Alexa fluor 680, Alexa fluor 750, Atto 680, and Atto 700, BODIPY, Brilliant Violet, Cyanine, Alexa, Atto, fluorescein, coumarin, rhodamine, xanthene fluorophore families and derivatives and combinations thereof.
Regarding claim 5, Oldenburg teaches a nanoparticle wherein “one or both of the shell and the intermediate shell comprises a metal or an inorganic metal oxide.” (Para. 23). Oldenburg teaches a nanoparticle wherein “the shell material is a polymer, metal, or metal oxide” (Para. 120) Thus, Oldenburg teaches a nanoparticle wherein the nanoparticle comprises an outer layer, wherein the outer layer comprises a metal, an inorganic oxide or a polymer.
Regarding claim 6, Oldenburg teaches a nanoparticle wherein “a bifunctional linker molecule or a biomolecule attached to a surface of each particle… a molecule selected from the group consisting of a protein, antibody, DNA, RNA and combinations thereof, wherein the molecule is bonded to a particle surface.” (Para. 26-27). Oldenburg also teaches a nanoparticle wherein “the nanoparticle may be further functionalized with a targeting moiety… The targeting moiety may include, but is not limited to, antibodies and fragments thereof, haptens, polypeptides, oligonucleotides, DNA, anti- sense RNA, peptide nucleic acids, proteins, chimeric and/or fusion proteins, and the like”(Para. 130) and “The targeting moiety may be attached to the surface of the coated nanoparticle via a linker” (Para. 131). “Direct linking of the targeting moiety implies only that functional groups on the coating surface of the particle and the targeting moiety itself serve as the points of chemical attachment” (Para. 132). Thus, Oldenburg teaches a nanoparticle wherein the nanoparticle comprises a coating, wherein the coating comprises: a. a repulsive component; and/or b. a linker; and/or c. a detection probe.
Regarding claim 7, Oldenburg teaches a nanoparticle wherein “the nanoparticles have a median maximum dimension that is less than 100 nm” (Para. 13). Thus, Oldenburg teaches nanoparticles have an average diameter of less than about 300 nm.
Conclusion
No claims are in condition for allowance.
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/KENDRA R VANN-OJUEKAIYE/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
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