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 .
DETAILED ACTION
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 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.
Response to Restriction/Election
Applicant’s election of the followings in response to election of species is acknowledged:
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Since Applicant did not traverse the restriction/election requirement, the election has been treated as an election without traverse. Applicants preserve their right to file a divisional on the non-elected subject matter.
Status of the claims
Claims 1-18 are examined on merits in this office action.
Claim Objections
Claims 1, 3-4, 10 and 14 are objected to for not being in proper Markush format. A Markush claim is commonly formatted as: “selected from the group consisting of A, B, and C”. When materials recited in a claim are so related as to constitute a proper Markush group, they may be recited in the conventional manner, or alternatively. For example, if “wherein R is a material selected from the group consisting of A, B, C and D” is a proper limitation, then “wherein R is A, B, C or D” shall also be considered proper (MEPP § 2173.05).
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 of this title, 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, 3-7, 10-11 and 12 are rejected under 35 U.S.C. 103 as obvious over Li et al. (Langmuir 2019; Cite # 2, in the IDS of 9/28/2023) in view of Badescu et al (Bioconjugate Chem. 2014).
In regards to claims 1, 3-7 and 12, Li discloses a surface having plurality of reaction zones
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for immobilization of his tag protein (6His-anti-HER2 antibody) wherein the surface is provided by utilizing sulfone based bifunctional linker (abstract). Li teaches that His-tagged protein immobilization via surface vinyl sulfoneimidazole coupling on solid supports lead to improved sensitivity of biosensors, as the protein is oriented in a more favorable way. Li teaches that the surface with immobilized sulfone provides site-directed immobilization of proteins (biological molecules) by means of a sulfone based cross-linking agent (= VS surface) that attaches the His tag Ab to the substrate (Au surface = substrate) via a functionalized EG6-OH SAM (= linker; figure 1 a, figure 5b). Such immobilization via surface vinyl sulfone-imidazole coupling on solid supports lead to improved sensitivity of biosensors, as the protein is oriented in a more favorable way (see "conclusions" on page 16473; bridging paragraph between pages 16471-16472).
Li does not disclose the use of a sulphone-based cross-linker having the structure of Formula (1 ) as claimed.
Badescu discloses trifunctional linker 4-[2,2-Bis[(p-tolylsulfonyl)methyl]acetyl) benzoic acid-NHS ester; bis-sulfone NHS; i.e
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; page 1133, 1st col) for providing conjugates of antibody with a drug molecule (Abstract). Badescu teaches that the linker is useful for providing covalent attachment of drug to targeting antibody (Introduction). Badescu teaches that the bis-reactive sulfone group (bis-alkylating group) is capable of undergoing reaction with both sulfur atoms derived from a reduced disulfide bond in antibodies and antibody fragments resulting in covalent rebridging via a three-carbon bridge leaving the protein (antibody) structurally intact and the resulting conjugates are stable and retained antigen-binding (Abstract and introduction). Badescu teaches that the three-carbon bridge is small enough and sufficiently flexible not to perturb the tertiary structure of the antibody (page 1126, 1st col.).
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Badescu teaches that the linker with the antibody can be conjugated to drugs to provide antibody-drug conjugate (ADC) to the fluorophores to provide fluorescent tagged antibody (Fir 2).
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The trifunctional linker is of the same trifunctional linker as claimed (see claim 1 and formula 4 of claim 4). Note that the trifunctional linker of Badescu comprises OH for R3 which is in activated form (NHS).
Therefore, from the description in mind of Li and Badescu, it would be obvious to ordinary skilled in the art to easily envisage considering the trifunctional linker of Badescu for surface immobilization of antibody in view of Li with the expectation of expanding the arsenal of linkers and immobilization processes of various antibodies with other linkers, in the method of Li with a reasonable expectation of success. One of ordinary skilled in the art from the reading would understand that for the sulfone linker of Li, the antibody needs to be tagged with 6His but however, the linker of Badescu, as described above, does not require tagging antibody with 6His becasue Badescu teaches that the bis-reactive sulfone group is capable of undergoing reaction with both sulfur atoms derived from a reduced disulfide bond in antibodies and antibody fragments resulting in covalent rebridging via a three carbon bridge leaving the antibody structurally intact and the resulting conjugates are stable and retained antigen-binding. Badescu also teaches that monoalkylation reagents leave the original disulfides unbridged, potentially introducing instability to the antibody (Introduction). Therefore, one of ordinary skilled in the art would be motivated to utilize that bis-alkylating group of the linker of Badescu for binding to various antibodies with ease with a reasonable expectation of success. Moreover, since Badescu teaches drugs or fluorophores can be conjugated with the antibody by utilizing the other functional group of the linker as shown in Fig,2, one of ordinary skilled in the art can easily envisage the other functional group for immobilization of the linker to discrete surface locations for immobilization of the antibody to the surfaces in view of Li with a reasonable expectation of success. Badescu discloses that the other functional group can be modified with various functional groups including activated form (e.g. NHS) and thus various surfaces can be utilized with appropriate modification for immobilization of antibody utilizing the linker of Badescu with a reasonable expectation of success.
In regards to claim 10, Li teaches surface wherein titanium and gold sequentially deposited onto silicon wafers (page 16468, 2nd para of 1st col.), thus disclosing substrate comprising silicon.
In regards to claim 11, Li teaches surfaces of surface plamon resonance (SPR) chips, which would be considered as bio-chip surface (page 16466, 1st col.).
Claims 1-7 and 10-18 are rejected under 35 U.S.C. 103 as being obvious over Li et al. (Langmuir 2019) in view of Badescu et al (Bioconjugate Chem. 2014) as applied to claims 1, 3-7, 10-11 and 12 above, and further in view of Mcdonnell et al (2016/0287718A1; cited in IDS of 9/28/2023).
Li in view of Badescu have been described above providing obviousness of utilizing the bis-alkylating linker of Badescu for immobilization of antibody to biosensor surface for detection of analyte. Li in view of Badesco, as described above, teach gold and titanium surface but however, do not teach utilization of various other commonly used surfaces useful for biosensors and sensor arrays including epoxy surfaces and do not specifically teach a detection process.
In regards to claims 2, Mcdonnell teaches conjugate of a specific binding molecule (domain I β2GP1) with PEG polymer (Abstract) via a linker wherein the preferred linker is
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(para [0081]). Mcdonnell teaches that the linker is conjugated to the linker via two cysteine residues derived from a disulfide gridge in the domain I β2GP1 polypeptide (Abstract; claim 16 and para [0137]). Mcdonnell teaches that domain I β2GP1 polypeptide bind to analyte anti- β2GP1 antibody for detection of the analyte (para [0033] and [0037]). Mcdonnell teaches that to use the domain I β2GP1 polypeptide conjugate of the Invention in the detection of antibodies in an individual, an immunoassay may be conducted, the domain I β2GP1 polypeptide conjugate is provided as a reagent, and the antibody is the target in the biological sample (para [0039]). Mcdonnell teaches that in the methods of the invention, domain I β2GP1 polypeptide conjugates of the Invention may be immobilized, by known techniques, onto a suitable solid phase, such as affinity column packing material, or a plastic surface such as a microtiter plate or a dipstick (para [0041]).
Hernandez teaches SiO2 surfaces for immobilization of antibody. Hernandez teaches various surface modification for using the surface as biosensor (para 2 of page 2). Hernandez teaches surface modification of SiO2 surface with alkoxysilane. Hernandez teaches that the alkoxy groups in alkoxysilanes react with hydroxyl (OH) groups on activated silicon oxides, thus forming a covalent-Si-O-Si bond [24], while the remainder of the molecule can bear a range of different functional groups to couple the bioreceptor and examples include aminosilanes (NH2-organosilanes), glycidosilanes (epoxy-organosilanes), and mercaptosilanes (SH-organosilanes). Hernandex teaches that amine terminated silanes are a good option for immune biosensors based on antibody–antigen specific binding as functional groups NH2 can couple to a carboxylic acid (COOH) from the heavy chain of antibodies, yielding amide formation. Hernandez teaches APTES and APDMS as commonly used aminosilanes for surface modification of SiO2 (pages 2-3 and Figs. 1 & 2).
Therefore, given the fact that surface immobilization with sulfone-based linker useful and common in the art (Li and Mcdonnell) and given the fact that Mcdonnell envisaged immobilization of binding partner to surface utilizing linker having bis-alkylating group for immunoassay detection of analytes and given the fact that various surfaces, including silane surfaces can be utilized, it would be obvious to one of ordinary skilled to easily envisage utilizing the linker having bis-alkylating groups (e.g.
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) as disclosed by Badesco and Mcdonnell on various surfaces, as for example, epoxy silane surface and silane surface modified with various function group, with the expectation of immobilization of antibody on the surfaces for immunoassay detections with a reasonable expectation of success. Since Badesco disclosed the linker having activated NHS group, one of ordinary skilled in the art can easily envisage utilizing silane surface having amine group as taught by Hermendez useful for immobilization. Moreover, Badesco discloses derivation of the functional groups with amine group and one of ordinary skilled in the art understands that epoxy group taught by Hernandez will react to amine group of the linker to form a covalent linkage. Moreover, since the basic concept of utilizing the linker has been found to be obvious in view of Li and Badescu and various surfaces for immobilization have been taught by Mcdonnell and Hennandez, various surfaces having various functional groups and derivation of the linker functional group with various group for optimized conjugation would be obvious and within the purview of one of ordinary skilled in the art.
In regards to method process of detection as claimed in claims 13-18, Mcdonnell teaches immunoassay detection involving contacting the antibody conjugate with a sample containing the analyte , removing the unbound analyte and detecting the bound analyte with a detectable label. Mcdonnell also teaches competitive immunoassays utilizing labeled antibody (labeled analyte) to compete with the analyte present in the sample for binding to conjugate antibody wherein the amount of label negatively corelates with the amount of analyte (anti-β2GP1) present in the sample. Mcdonnell teaches detectably label includes enzyme label. (para [0043]; [0148]). Mcdonnell teaches various samples, including plasma.
Therefore, from the description in mind of Mcdonnell, one of ordinary skilled in the art can envisage that the solid support based immunoassay with the linker immobilized antibody would involve similar contacting, removing and detecting step with labeled antibody or labeled analyte and various samples and various types of common and known immunoassay method steps for detection of the various analytes with the immobilized linker would be obvious to one of ordinary skilled in the art.
Claims 1-18 are rejected under 35 U.S.C. 103 as being obvious over Li et al. (Langmuir 2019) in view of Badescu et al (Bioconjugate Chem. 2014) and Mcdonnell et al (2016/0287718A1) as applied to claims 1-7 and 10-18 above, and further in view of Fitzgerald et al (WO2017/085509A1).
Li in view of Badescu and Mcdonnell have been described above providing obviousness of utilizing the bis-alkylating linker of Badescu for immobilization of antibody to biosensor surface for detection of analyte utilizing various immunoassay processes. Li in view of Badesco and Mcdonnell as described above, teach biosensor surface of gold and titanium having plurality of reaction zones for immobilization of antibody but however, do not teach utilization of various other commonly used surfaces useful for biosensors and sensor arrays having masking/coating material on the surface wherein the reaction zones are uncoated and also does not teach the masking material further comprises a pigment.
In regards to claims 8-10, Fitzgerald teaches biosensor substrates (e.g. microarray) having plurality of reaction zones (page 1 and claims 1 and 10) wherein the substate comprises a coating of a masking material, and plurality of discrete reaction zones onto which one or more binding agents are intended to be covalently attached and wherein zones are uncoated areas on the substrate (page 2, lines 5-8). Fitzgerald teaches that it has surprisingly been found that the coated substrate provides improved detection sensitivity and image quality. Fitzgerald teaches the coated areas of the substrate reduce non-specific binding and the cross-linking of the spots and so background noise is reduced resulting in an enhanced signal-to-noise ratio (page 2, lines 10-14; page 3, line 20 to page 4, line 6). Fitzgerald teaches various types of substates including metal oxides, ceramic, glass and plastic (page 3, line 20 to page 4, line 6) and various types of resin for coating including acrylics and teaches that the coating may contain any suitable ink solvent and/or ink additive (page 4, lines 27-34 and claims 1,10-12, 13, 23 and 24). Fitzgerald further teaches that the masking material has a contact angle of 60-120⁰C (claim 13).
Therefore, given the fact that coating/masking, preferably with coating composition comprising black pigment in the area outside of reaction zones are useful for providing biosensor surfaces including microarray surfaces that provides improved detection sensitivity and image quality by reducing background noise resulting in an enhanced signal-to-noise ratio (Fitzgerald), it would be obvious to one of ordinary skilled in the art to easily envisage utilizing the coating composition and various sensor substrates in the method of detection as found obvious in view of Li, Badescu and McDonnell with a reasonable expectation of success.
Conclusion
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/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678
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