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 .
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.
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 1-8, 12-13,16,18-21,23-25 and 35-36 are rejected under 35 U.S.C. 103 as being unpatentable over Mrksich et al. (US 2014/0206570) in view of Nishimi et al. (US 2007/0266775).
Mrksich teaches a self-assembled monolayer-substrate composition (para 19), comprising: a self-assembled monolayer (SAM) attached to at least a portion of the substrate surface (para 19; alkanethiolates on a metal substrate), wherein the SAM comprises an alkyl chain having a reactive group at one terminus for association with the substrate surface (para 19, alkanethiolates, fig. 6).
Mrksich does not teach at least a portion of the SAM further comprising a traceless linker that is capable of reacting with an analyte upon exposure to ultraviolet light (this limitation does not positively recite exposing the SAM to ultraviolet light).
Nishimi teaches a biosensor wherein a biomolecule is immobilized on the surface of said biosensor (para 28-33), comprising a self assembled monolayer that further comprises a traceless linker (para 41-44, a compound generating a reactive group as a result of external stimulus preferably binds to a metal film coated with a self assembled monolayer), that is capable of reacting with an analyte (para 47-48; physiologically active substance) upon exposure to ultraviolet light (para 33 states a compound generating a radical by light; UV taught in para 98; compounds having a diazo group or a diazirine ring which is a traceless linker as indicated by the instant claim 6). Mrksich and Nishimi both are directed to self assembled monolayers to which biomolecules are bound, and specifically teach alkyl chain SAM such as alkanethiol with alkyl chain. It would have been obvious to one having an ordinary skill in the art at the time of the invention to modify Mrksich in view of Nishimi to employ a photoreactive diazirine traceless linker on the self assembled monolayers in order to enhance the ease of attaching a biomolecule to said monolayer using a safe raw material as taught by Nishimi (para 9-10; 39).
Regarding claim 2, the composition of claim 1, wherein the SAM comprises the alkyl chain and a spacer group, with at least a portion of the SAM further comprising the traceless linker (para 33 states a compound generating a radical by light; UV taught in para 98; compounds having a diazo group or a diazirine ring which is a traceless linker as indicated by the instant claim 6). It would have been obvious to one having an ordinary skill in the art at the time of the invention to modify Mrksich in view of Nishimi to employ a photoreactive diazirine traceless linker on the self assembled monolayers in order to enhance the ease of attaching a biomolecule to said monolayer using a safe raw material as taught by Nishimi (para 9-10; 39).
Regarding claim 3, the composition of claim 2, wherein the spacer comprises two to twenty ethylene glycol groups. Mrksich teaches that the spacer comprises two to twenty ethylene glycol groups (para 25, oligo (ethylene glycol) oligomer preferably contains 3-7 units, see fig. 6a)
Regarding claim 4, the composition of claim 2, wherein the spacer has a structure of
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wherein EG is ethylene glycol, and n is 2-20 (see fig. 6a, b which shows ethylene glycol with n being between 2-20).
Regarding claim 5, the composition of claim 4, wherein n is 2-5 (Mrksich, para 16).
Regarding claim 6, the composition of claim 1, wherein the traceless linker comprises a diazirine (the modified Mrksich teaches diazirine as the traceless linker as seen above. Nishimi, para 33 states a compound generating a radical by light; UV taught in para 98; compounds having a diazo group or a diazirine ring which is a traceless linker).
Regarding claim 7, the composition of claim 1, wherein the traceless linker comprises 3-trifluoromethyl-3-phenyl-diazirine (TPD) (See Nishimi which further teaches the traceless linker of diazirine can be 3-trifluoromethyl-3-phenyl-diazirine as seen in para 39 A-1).
Regarding claim 8, the composition of claim 1, wherein the traceless linker forms a carbene upon exposure to ultraviolet light (the same traceless linker as seen in claim 6 and 7 is taught by the modified Mrksich. Claim 8 is a product by process which does not further limit the instant claim. Further Mrksich applies a UV light and therefore the traceless linker would form a carbene from exposure due to the same composition being claimed. Nishimi teaches carbene, para 39).
Regarding claim 12, the composition of claim 1, wherein the density of traceless linker is from about 0.1% to 100% (The modified Mrksich teaches the same diazirine ring and is present within the above density of the composition as seen in Nishimi, para 39).
Regarding claim 13, which depends from claim 1, wherein the density of traceless linker is from about 10% to about 50% (Mrksich teaches the density of the linker is about 10 to the 10th molecules /Cm2).
Regarding claim 16, the composition of claim 1, wherein the traceless linker is attached to the SAM (the modified Mrksich applies the traceless linker diazirine attached to the SAM via a complementary reactive group on the SAM) via reaction of complementary reactive groups on the SAM and on the traceless linker (this limitation is directed to a product by process limitation and is not given further weight in claims directed toward a product composition).
Regarding claim 18, Mrksich teaches a method of making the composition of claim 1, comprising
contacting the substrate with the alkyl chain having a reactive group at one terminus to attach the alkyl chain to at least a portion of the substrate surface to form the SAM (para 19; alkanethiolates with alky chain are attached to a metal substrate; fig. 6); wherein at least a portion of alkyl chains of the SAM further comprise a spacer (amine, carboxylic acid, thiol, or maleimide, para 26)
wherein at least a portion of alkyl chains of the SAM further comprise a spacer group (ligand is immobilized onto the SAM via spacer or reactive group of an amine, carboxylic acid, thiol, or maleimide , para 26).
Mrksich does not teach a traceless linker and contacting the reactive group and the traceless linker to attach the traceless linker via a complementary reactive group on the traceless linker.
Nishimi teaches a biosensor wherein a biomolecule is immobilized on the surface of said biosensor (para 28-33), comprising a self assembled monolayer that further comprises a traceless linker (para 41-44, a compound generating a reactive group as a result of external stimulus preferably binds to a metal film coated with a self assembled monolayer), that is capable of reacting with an analyte (para 47-48; physiologically active substance) upon exposure to ultraviolet light (para 33 states a compound generating a radical by light; UV taught in para 98; compounds having a diazo group or a diazirine ring which is a traceless linker as indicated by the instant claim 6). Mrksich and Nishimi both are directed to self assembled monolayers to which biomolecules are bound, and specifically teach alkyl chain SAM such as alkanethiol with alkyl chain. It would have been obvious to one having an ordinary skill in the art at the time of the invention to modify Mrksich in view of Nishimi to employ a photoreactive diazirine traceless linker on the self assembled monolayers in order to enhance the ease of attaching a biomolecule to said monolayer using a safe raw material as taught by Nishimi (para 9-10; 39).
Regarding claim 19, the method of claim 18, wherein the reactive group on the traceless linker comprises a maleimide (Mrksich, para 16, 26, 32).
Regarding claim 20, the method of claim 18, wherein the reactive group on the alkyl chain or the reactive group on the traceless linker comprises an azide, an alkyne, a maleimide (para 49), a thiol (para 26), an alcohol, an amine (para 26), a carboxylic acid (para 26), an olefin, an isothiocyanate, a N- hydroxysuccinimide, a phosphine, a nitrone, a norbornene, an oxanorbornene, a transcycloctene, an s-tetrazene, an isocyanide, a tetrazole, a nitrile oxide, a quadricyclane, or a carbodiimide to react with the maleimide.
Regarding claim 21, the method of claim 20, further comprising contacting the composition and an analyte under ultraviolet light to attach the analyte (para 33 states a compound generating a radical by light; UV taught in para 98; compounds having a diazo group or a diazirine ring which is a traceless linker).
Regarding claim 23, the method of claim 21, wherein the analyte comprises a protein (para 4-5), a peptide (para 4-5), an antibody, an oligonucleotide, a small molecule, a carbohydrate, a metabolite, an amino acid (para 4-5), a fatty acid, a lipid (para 4-5), a drug, or a reaction product.
Regarding claim 24, MrKsich teaches a method of measuring activity of an enzyme, comprising
(a) contacting the enzyme with an enzyme analyte to form a reaction mixture (para 8, 14); wherein the enzyme analyte, upon contact with the enzyme, forms a product, such that the enzyme analyte and the product comprise different masses (para 54);
(b) contacting the reaction mixture of (a) with the composition of claim 1 (see the rejection of claim 1 of MrKsich in view of Nishimi) such that the enzyme analyte and the product are attached to the composition via reaction with the traceless linker in the presence of ultraviolet light (para 33 states a compound generating a radical by light; UV taught in para 98; compounds having a diazo group or a diazirine ring which is a traceless linker);
(c) subjecting the composition to mass spectrometry to produce a mass spectrum having an enzyme analyte signal and a product signal (para 4, 17, 29-31) and
(d) measuring the activity of the enzyme by correlating a signal intensity of the enzyme analyte signal to a signal intensity of the product signal to determine the extent of product formation and thereby measuring the activity of the enzyme (para 17, kinetic profile for the enzymatic reaction; para 17,29-31).
Regarding claim 25, the method of claim 24, wherein the enzyme is a deacetylase, acetyltransferase, esterase, phosphorylase/kinase, phosphatase, protease, methylase, demethylase, or a DNA or RNA modifying enzyme (PRMT1 enzyme, para 16).
Regarding claim 35, MrKsich teaches a method of monitoring a chemical reaction, comprising
(a) contacting two or more reactants of the chemical reaction to form a reaction mixture; wherein the two or more reactants, upon contact, forms a product, such that the reactants and the product comprise different masses;
(b) contacting the reaction mixture (para 15) of (a) with the composition of claim 1 (see the rejection of claim 1 of MrKsich in view of Nishimi) such that the reactant and the product are attached to the composition via reaction with the traceless linker in the presence of ultraviolet light (para 33 states a compound generating a radical by light; UV taught in para 98; compounds having a diazo group or a diazirine ring which is a traceless linker);
(c) subjecting the composition to mass spectrometry to produce a mass spectrum having a product signal and reactant signals, one for each reactant (para 36); and
(d) monitoring the chemical reaction by correlating a signal intensity of at least one of the reactant signals to a signal intensity of the product signal to determine the extent of product formation and thereby monitoring the chemical reaction (para 61, fig. 7).
Regarding claim 36, the method of claim 35, the modified MrKsich does not teach wherein the chemical reaction is a Suzuki reaction, and the two or more reactants comprise an organoboron and a halide compound.
Nishimi teaches the compound generating reactive group as a result of light irradiation which generate a radical include aromatic halide compounds and active species which are fully incorporated document “Summary of S. A. Flemig, Tetrahedron, Vol. 51, pp. 12479-12520, 1995, and Summary of Yasumaru Hatanaka, Journal of Synthetic Organic Chemistry, Japan, Vol. 56, pp. 581-590, 1998.” It would have been obvious to one having an ordinary skill in the art at the time of the invention to modify the modified Mrksich to employ a reactive group from above due to the compounds ability to be a reactive group which results from the application of light irradiation as taught by Nishimi.
Response to Arguments
Applicant's arguments filed 9/19/25 have been fully considered but they are not persuasive.
Applicant argues, “The Office asserted that the reason to combine would be to "enhance the ease of attaching a biomolecule" to a SAM using "a safe raw material" but the Office has pointed to nothing in Mrksich or Nishimi suggesting that such asserted improvements over Mrksich were needed or desired.”
Mrksich teaches a biochip having a self assembled monolayer with a reactive group at the terminus of an alkyl chain for reacting with an analyte. Mrksich does not teach a tracerless linker. Nishimi which is in the analogous art of self assembled monolayers biosensors, teaches a biosensor having a self assembled monolayer having a compound generating a reactive group as a result of an external stimulus binds to a metal film coated with a self assembled monolayer. Nishimi teaches the traceless linker is a diazirine ring or diazo group. The instant claims recite a traceless linker that comprises a diazirine as seen in claim 3 and 6. Therefore the traceless linker of Nishimi is structurally capable of reacting with an analyte when presented. Claim 1 has not positively claim that an analyte is present and is then reacted with the linker to produce a reaction product or further compound. Claim 1 states that the traceless linker is capable of reacting with an analyte upon exposure to UV light. Nishimi states since these photoreactive compounds have their own characteristics, they may be selected and used depending on use conditions. From the viewpoint of relatively high safety, a compound having a diazirine ring is preferable. (para 39). It would have been obvious to one having an ordinary skill in the art at the time of the invention to modify Mrksich in view of Nishimi to employ a photoreactive diazirine traceless linker on the self assembled monolayers in order to enhance the ease of attaching a biomolecule to said monolayer using a safe raw material as taught by Nishimi (para 9-10; 39). That is, one would have chosen a traceless linker such asdiazirine due to the safety when irritated by light to react to produce a biosensor that can measure a substance in a sample solution (para 39, 80-81).
Applicant argues, “The Office's interpretation of Nishimi's disclosure is inconsistent with the arrangement of elements as recited in the instant claims. In their analysis of Nishimi, the Office appears to merge the claim elements "traceless linker" and "analyte" without considering the distinct roles that each element serves.” Claim 1 does not positivily recite an analyte. Claim 1 is directed to the SAM substrate that is capable of interacting with an analyte. The rejection is based upon the construction of Mrksich in view of Nishimi to teach this SAM substrate composition that is capable of interacting with an analyte. Since the rejection composes each element of the claimed SAM substrate it would be structurally capable of reacting with an analyte. The “traceless linker” is the same linker of the instant claims and would thereby be capable of interacting with an analyte. See MPEP 2112.01. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). “Products of identical chemical composition can not have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
Applicant argues, “There is no subsequent UV light treatment to attach CA to the Compound, nor any intervening step facilitating the attachment of CA to the Compound. Use of UV light to attach a SAM comprising a Compound to a substrate and subsequent attachment of CA to the Compound is not equivalent to the claim-recited traceless linker that is capable of reacting with an analyte upon exposure to UV light. Thus, Nishimi teaches a method comprising use of a photo-immobilizer and UV light to attach a SAM to a gold-substrate surface, followed by application of an analyte and subsequent quantification. Claim 1 does not positively recite applying UV light or applying UV light. Claim 1 is directed to the SAM substrate composition.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMUEL P SIEFKE whose telephone number is (571)272-1262. The examiner can normally be reached Monday, Tuesday, Thursday, Friday, 8-6.
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/SAMUEL P SIEFKE/Primary Examiner, Art Unit 1758