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 with traverse of Group 1, claims 16-25 and 32 in the reply filed on 11/19/2025 is acknowledged. The traversal is on the ground(s) that: the office action’s lack of unity determination is contrary to the position of the ISA and the “special technical feature” defines a contribution without requiring modification of the prior art. This is not found persuasive because the technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Grant in view of Kalkum as discussed in the Office Action filed 09/22/2025. Note that “prior art” does not preclude multiple prior art references or modification of the prior art to arrive at the claimed special technical features. MPEP 1893.03(d) discusses the expression special technical features is defined as meaning those technical features that define the contribution which each claimed invention, considered as a whole, makes over the prior art.
The requirement is still deemed proper and is therefore made FINAL.
Claims 26-31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 11/19/2025. Note that claims 26-31 are cancelled.
Claim Objections
Claim 16 is objected to because of the following informalities: In claim 1, line 9, it is suggested to recite “FRET” in an unabbreviated form to establish the acronym. 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.
Claim 25 is 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.
Regarding claim 25, claim 25 recites “at least part of which is transparent” in line 3. It is unclear which element “of which” is referring to. Is “of which” referring to the exploration head, body, or emission face?
Claim Rejections - 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 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 the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 16-18, 20-21, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Grant et al. (GRANT et al., "Effects of immobilization on a FRET immunosensor for the detection of myocardial infarction", ANAL. BIOANAL. CHEM., vol 381, No. 5, March 2005, pages 1012-1018, XP019327187; cited in the IDS filed 03/10/2023) in view of Kalkum et al. (US 20090176259 A1).
Regarding claim 16, Grant teaches a device (abstract and Figs. 1-2 teach an optical biosensor) for detecting a target molecule and/or measuring the concentration of a target molecule (interpreted as an intended use of the device, see MPEP 2114; abstract and Figs. 3-5 teach the optical biosensor is for detecting a target molecule and concentration response of the biosensors) comprising:
a substrate (Figs. 1-2 and page 1014, sections “preparation of optical fibers” and “treatment of fibers with MTS and GMBS” teach silica fibers, i.e. substrate) at the surface of which a grafting molecule is covalently attached (page 1014, sections “preparation of optical fibers” and “treatment of fibers with MTS and GMBS” teach silanization was used as the immobilization technique, where the silica fibers were silanized and treated with MTS and GMBS; therefore, the surface has a grafting molecule that includes silane and GMBS covalently bonded to the surface);
at least one fluorescent probe (Fig. 1; page 1013, section “Materials”) comprising:
at least one receptor (antibody) bonded to a polypeptide (protein A);
two fluorochromes Fa (donor fluorophore) and Fb (acceptor fluorophore);
wherein the fluorochrome Fa is bonded to the receptor (Fig. 1 teaches “antibody-donor”, where the donor fluorophore is bonded or attached to the antibody) and the fluorochrome Fb is bonded to the polypeptide (Fig. 1 teaches “protein A-acceptor”, where the acceptor fluorophore is bonded or attached to the protein A); and
the fluorochromes Fa and Fb form a FRET donor/acceptor pair (Fig. 1 teaches a FRET immunosensor; page 1013, second full paragraph teaches the FRET biosensor formed from the donor and acceptor fluorophores, therefore the donor and acceptor fluorophores form the FRET donor/acceptor pair);
wherein the polypeptide is bonded to the grafting molecule (page 1014, section “immobilization of PA and antibody” teaches the protein A was immobilized to the silanized fibers, therefore the protein A is bonded to the grafting molecule of the fiber surface).
Grant fails to teach: the at least one receptor bonded to the polypeptide via a covalent bond; wherein the polypeptide is bonded to the grafting molecule via a covalent bond.
Grant teaches protein A was immobilized to the silanized fibers (page 1014, section “immobilization of PA and antibody”).
Kalkum teaches an assay for detection of toxin or enzyme (abstract). Kalkum teaches antibodies are cross-linked to protein A (paragraph [0012]; Fig. 1), wherein cross-linking is implied to have a covalent bond. Kalkum teaches embodiments comprising a FRET pair with a donor and acceptor (paragraph [0074]). Kalkum teaches immobilization of antibodies to a matrix can be by a variety of methods, such as covalent crosslinking (paragraph [0041]). Kalkum teaches antibodies covalently linked to a protein A support (paragraph [0055]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the fluorescent probe of Grant to incorporate Kalkum’s teachings of bonding an antibody with a protein of (Fig. 1; paragraph [0012]) and covalent crosslinking of antibodies with a matrix or support (paragraphs [0041],[0055]) and Grant’s teachings of protein A was immobilized to the silanized fibers (page 1014, section “immobilization of PA and antibody”) to provide: the at least one receptor bonded to the polypeptide via a covalent bond; wherein the polypeptide is bonded to the grafting molecule via a covalent bond. Doing so would have a reasonable expectation of successfully improving attaching the receptor with the polypeptide and the polypeptide to the grafting molecule of the substrate.
Furthermore, the claimed limitations are obvious because all of the claimed elements were known in the prior art and one skilled in the art could have combined the elements (i.e. bonding of the claimed elements via a covalent bond) by known methods with no change in their respective functions, and the combinations yielded nothing more than predictable results (i.e. providing the elements bonded via a covalent bond would yield nothing more than the obvious and predictable result of improving attaching the receptor with the polypeptide and the polypeptide to the grafting molecule of the substrate See MPEP 2143(A).
Regarding claim 17, Grant further teaches wherein the receptor is chosen from antibody, antibody fragment, aptamer, peptides, or a derivative thereof (Fig. 1, antibody).
Regarding claim 18, Grant further teaches wherein the polypeptide is a binding protein chosen from protein G, protein L, protein A, protein Z, protein M, immunoglobulin, a complete or partial immunoglobulin, or a derivative thereof (Fig. 1, protein A).
Regarding claim 20, Grant further teaches wherein the fluorochromes Fa (Fig. 1; page 1013, section “Materials”, donor fluorophore) and/or Fb (Fig. 1; page 1013, section “Materials”, acceptor fluorophore) are chosen from fluorescent molecules or fluorescent proteins (page 1013, section “Materials” teaches Alexa Fluor 546 (AF546) and Alexa Fluor 594 (AF594) are used as the donor and acceptor fluorophores, i.e. fluorescent molecules).
Regarding claim 21, Grant further teaches wherein the substrate is chosen from a cell culture plate, a well plate, a film, a strip, an agarose gel, a cellulose gel, nanoparticles or microparticles, a microscope slide, a glass strip, the periphery of an optical fibre or a substrate configured to be attached to head of an optical fibre (Figs. 1-2 and page 1014, sections “preparation of optical fibers” and “treatment of fibers with MTS and GMBS” teach silica fibers, i.e. the periphery of an optical fibre or a substrate configured to be attached to head of an optical fibre).
Regarding claim 24, Grant further teaches wherein the grafting molecule (page 1014, sections “preparation of optical fibers” and “treatment of fibers with MTS and GMBS” teach silanization was used as the immobilization technique, where the silica fibers were silanized and treated with MTS and GMBS; therefore, the surface has a grafting molecule that includes silane and GMBS covalently bonded to the surface) comprises at least two reactive groups chosen from maleimide, N- Hydroxysuccinimide (NHS) ester, sulfo N-hydroxysuccinimide ester, sulfo-NHS, azide, alkyne, epoxide, carboxylic acid, aldehyde, aziridine, alkene, or a derivative thereof (page 1014, sections “preparation of optical fibers” and “treatment of fibers with MTS and GMBS” teach silanization was used as the immobilization technique, where the silica fibers were silanized and treated with MTS and GMBS; therefore the grafting molecule including GMBS, which structurally includes maleimide and NHS ester groups).
Claims 19 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Grant in view of Kalkum as applied to claim 16 above, and further in view of Wilson et al. (US 20210178290 A1; effectively filed 04/18/2018).
Regarding claim 19, while Grant teaches the polypeptide is protein A (abstract), modified Grant fails to teach: wherein the polypeptide comprises between 2 and 100 amino acids.
Wilson teaches detection of analytes in a flow cell using fluorescence (abstract). Wilson teaches detection of fluorescence intensity can use multiple molecular recognitions agents recognizing the target, which interact by FRET (paragraph [0030]). Wilson teaches a recognition element can be proteins including but not limited to protein A or short peptide chain with the specific binding capability, such as TWKTSRISIF (SEQ ID NO: 1) and RRGW (SEQ ID NO: 16), which comprises 10 and 4 amino acids respectively (paragraph [0013]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the polypeptide of modified Grant to incorporate the teachings of polypeptides comprising between 2 and 100 amino acids of Wilson (paragraph [0013]) to provide: wherein the polypeptide comprises between 2 and 100 amino acids. Doing so would have a reasonable expectation of successfully improving recognition of desired targets a taught by Wilson.
Additionally, since Wilson teaches known alternatives of polypeptides to Protein A, such as comprising between 2 and 100 amino acids of Wilson (paragraph [0013]), it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Grant to incorporate the teachings of polypeptides comprising between 2 and 100 amino acids of Wilson (paragraph [0013]) to provide: wherein the polypeptide comprises between 2 and 100 amino acids. I.e. It would have been obvious to have substituted one known element (Grant’s Protein A) for another (Wilson’s short peptides having 4 or 10 peptides), and the results of the substitution would have been predictable (allowing for detection of a desired target via FRET). See MPEP 2143(I)(B).
Regarding claim 32, modified Grant fails to teach: wherein the polypeptide comprises between 4 and 50 amino acids.
Wilson teaches detection of analytes in a flow cell using fluorescence (abstract). Wilson teaches detection of fluorescence intensity can use multiple molecular recognitions agents recognizing the target, which interact by FRET (paragraph [0030]). Wilson teaches a recognition element can be proteins including but not limited to protein A or short peptide chain with the specific binding capability, such as TWKTSRISIF (SEQ ID NO: 1) and RRGW (SEQ ID NO: 16), which comprises 10 and 4 amino acids respectively (paragraph [0013]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the polypeptide of modified Grant to incorporate the teachings of polypeptides comprising between 4 and 50 amino acids of Wilson (paragraph [0013]) to provide: wherein the polypeptide comprises between 4 and 50 amino acids. Doing so would have a reasonable expectation of successfully improving recognition of desired targets a taught by Wilson.
Additionally, since Wilson teaches known alternatives of polypeptides to Protein A, such as comprising between 4 and 50 amino acids of Wilson (paragraph [0013]), it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Grant to incorporate the teachings of polypeptides comprising between 4 and 50 amino acids of Wilson (paragraph [0013]) to provide: wherein the polypeptide comprises between 4 and 50 amino acids. I.e. It would have been obvious to have substituted one known element (Grant’s Protein A) for another (Wilson’s short peptides having 4 or 10 peptides), and the results of the substitution would have been predictable (allowing for detection of a desired target via FRET). See MPEP 2143(I)(B).
Claims 22-23 are rejected under 35 U.S.C. 103 as being unpatentable over Grant in view of Kalkum as applied to claim 21 above, and further in view of Loeb et al. (US 20070010726 A1).
Regarding claim 22, modified Grant fails to teach: wherein the substrate is a polymer film.
Loeb teaches a biosensing device for detecting biological analytes, wherein the device comprises an optical fiber, and light from fluorescent molecules are analyzed (abstract; Figs. 1-2). Loeb teaches the optical fiber has an end comprising a polymer matrix and at least one fluorescent molecule covalently bound to the polymer matrix upon interaction with a molecule (paragraph [0010]). Loeb teaches a biosensing material comprises an analyte-specific biomolecule immobilized in a polymer matrix which is in contact with the internal end of the transmitting member, wherein analytes bind to the biosensing material and results in fluorescent changes (paragraph [0044]; Figs. 1-2). Loeb teaches coatings could be applied to the outer surface of the optical fiber or transmitting member to enhance the attachment of the biosensing material and/or the containment matrix thereto (paragraphs [0060]-[0061]); and these coatings may facilitate a stable interface between the transmitting member and the biosensing material such that these components of the device remain in operative communication; and these coatings may encourage a stable interface between the transmitting member and the containment matrix, so that where desired, the biosensing material is isolated from the patient tissue and reaction products are maintained in a concentrated area for detection (paragraph [0061]). Loeb teaches a typical Teflon outer jacket, i.e. polymer film, provides a surface that binds tightly to PEG derivatives that have been end-functionalized (paragraph [0061]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the substrate of modified Grant to incorporate the teachings of biosensing devices comprising an optical fiber with a Teflon outer jacket and polymer matrix of Loeb (paragraphs [0010],[0044],[0060]-[0061]) to provide: wherein the substrate is a polymer film. Doing so would have a reasonable expectation of successfully enhancing the attachment of a biosensing material and/or the containment matrix to the substrate, facilitating a stable interface between a transmitting member and biosensing material, and therefore improving sensing as taught by Loeb (paragraphs [0060]-[0061]).
Regarding claim 23, modified Grant fails to teach: wherein the polymer film is chosen from polyethylene terephthalate, fluorinated polyethylene-co-propylene, polymethylmethacrylate, polytetrafluoroethylene, polymethylpentene, polyvinyl chloride, styrene methyl methacrylate, polyethylene naphthalate, derivatives thereof or a mixture thereof.
Loeb teaches a biosensing device for detecting biological analytes, wherein the device comprises an optical fiber, and light from fluorescent molecules are analyzed (abstract; Figs. 1-2). Loeb teaches the optical fiber has an end comprising a polymer matrix and at least one fluorescent molecule covalently bound to the polymer matrix upon interaction with a molecule (paragraph [0010]). Loeb teaches a biosensing material comprises an analyte-specific biomolecule immobilized in a polymer matrix which is in contact with the internal end of the transmitting member, wherein analytes bind to the biosensing material and results in fluorescent changes (paragraph [0044]; Figs. 1-2). Loeb teaches coatings could be applied to the outer surface of the optical fiber or transmitting member to enhance the attachment of the biosensing material and/or the containment matrix thereto (paragraphs [0060]-[0061]); and these coatings may facilitate a stable interface between the transmitting member and the biosensing material such that these components of the device remain in operative communication; and these coatings may encourage a stable interface between the transmitting member and the containment matrix, so that where desired, the biosensing material is isolated from the patient tissue and reaction products are maintained in a concentrated area for detection (paragraph [0061]). Loeb teaches a typical Teflon outer jacket, i.e. polytetrafluoroethylene film, provides a surface that binds tightly to PEG derivatives that have been end-functionalized (paragraph [0061]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the substrate of modified Grant to incorporate the teachings of biosensing devices comprising an optical fiber with a Teflon outer jacket and polymer matrix of Loeb (paragraphs [0010],[0044],[0060]-[0061]) to provide: wherein the polymer film is chosen from polytetrafluoroethylene. Doing so would have a reasonable expectation of successfully enhancing the attachment of a biosensing material and/or the containment matrix to the substrate, facilitating a stable interface between a transmitting member and biosensing material, and therefore improving sensing as taught by Loeb (paragraphs [0060]-[0061]).
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Grant in view of Kalkum as applied to claim 16 above, and further in view of Tan et al. (US 20050254062 A1).
Regarding claim 25, Grant further teaches the device according to claim 16, further comprising an optical fibre (Fig. 2, “fiber”) and an exploration head (Fig. 2, sensing tip). Modified Grant fails to teach: wherein said exploration head comprises a body and an emission face, at least a part of which is transparent forming a port, the substrate being said port.
Tan teaches an apparatus for detecting the presence or amount of an analyte in a sample solution, the apparatus including an optical assembly and a surface formed by a layer of analyte binding molecules (abstract). Tan teaches the apparatus is based on fiber optic interferometry (paragraph [0004]). Tan teaches an exploration head (Figs. 1-2) comprises a body (body of optical fiber 32) and an emission face (face of transparent optical element 38), at least a part of which is transparent forming a port, i.e. substrate, (Fig. 2 and paragraph [0054] teaches a transparent optical element 38 which is interpreted as forming a port or substrate at the end of the optical fiber 32). Tan teaches the transparent optical element in the assembly allows for detection of analyte via measurement of change in interference of light (paragraphs [0012]-[0014]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified said exploration head of modified Grant to incorporate the teachings of an optical assembly with an exploration head including a transparent port or substrate of Tan (Figs. 1-2; paragraphs [0004],[0012]-[0014],[0054]) to provide: wherein said exploration head comprises a body and an emission face, at least a part of which is transparent forming a port, the substrate being said port. Doing so would have a reasonable expectation of successfully improving optical transmission and detection of desired light for detection of an analyte as taught by Tan.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Chaney et al. (US 20050255327 A1) teaches articles having bioactive surfaces (paragraph [0003]). Chaney teaches articles may include a sensing end of a fiber coated with a monomer, a polymer matrix coupled to the monomer, and a biological functional molecule covalently bound to the polymer matrix (paragraph [0045]). Chaney teaches monomer-deposited substrates or articles can be made of any polymer, such as polymethylpentene (paragraph [0052]). Chaney teaches the substrates may be optically transparent for biosensors (paragraph [0057]).
Potyrailo et al. (US 20060198760 A1) teaches a device that includes a sensor layer disposed on a substrate to interact with or react with a target species (abstract). Potyrailo teaches the substrate includes optical waveguides, such as optically transmissive fibers or plates (paragraph [0019]). Potyrailo teaches a sensor layer may be transparent (paragraph [0025]). Potyrailo teaches a sensor layer may include an immobilized dye in a polymer film coated onto a planar waveguide or on the end of an optical fiber (paragraph [0040]).
Nicolaides et al. (US 20210285960 A1; effectively filed 09/27/2018) teaches protein structural probes (abstract; Fig. 1). Nicolaides teaches an example of a probe and their approximate binding regions, wherein probes comprising conjugated paired dyes or fluors may be used to in FRET analysis (Fig. 1; paragraph [0039]). Nicolaides teaches the antibody includes a PA or PG, and donor and acceptor fluorophores (Fig. 1; paragraph [0039]).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HENRY H NGUYEN whose telephone number is (571)272-2338. The examiner can normally be reached M-F 7:30A-5:00P.
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/HENRY H NGUYEN/Primary Examiner, Art Unit 1758