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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on January 86 has been entered. Claims 11-13 and 15-16 are pending in the application.
Status of Objections and Rejections
The rejection of claims 17-20 and 22-24 is obviated by Applicant’s cancellation.
All rejections from the previous office action are maintained.
New grounds of rejection are necessitated by the amendments.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 11-13 and 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mao (US 20160296147) in view of Gregg (US 5,320,725), supported by “Thioglycolic Acid_ PubChem” as an evidence.
Regarding claim 11, Mao teaches a method for preparing a glucose electrochemical sensor ([Abstract]: electrochemical sensors), which is based on a hydrogel of a cationic (¶5: the coating is preferably not soluble in water, though it may swell in water; ¶57: X represents counter ion(s) and is a halide, such as chloride; thus the polymer is cationic) redox polymer ([Abstract]: transition metal complexes attached to polymeric backbones) containing a transition metal complex medium ([Abstract]: transition metal complexes), wherein the method comprises the following steps:
A. reacting the transition metal complex medium with a nitrogen-containing heterocyclic compound (e.g., p. 15, ¶105, Formula 21 indicates the transition metal complex are coupled to the nitrogen-containing heterocyclic compound) and a terminal mercapto alkyl acid (¶40: a substituted functional group (e.g., substituted alkyl) include mercapto; ¶67: R8, R9, and R10 are independently -COOH, -SH, etc.) to obtain a short-chain graftable molecule containing the transition metal complex; said terminal mercapto alkyl acid being thioglycolic acid (as evidenced by PubChem, thioglycolic acid has a molecular formula HS-CH2-COOH, and is also called mercaptoacetic acid);
said nitrogen-containing heterocyclic compound being one or more of vinylimidazole, allyl imidazole (Formula 4,5; ¶65: suitable heterocyclilc monodentate ligands include substituted and unsubstituted imidazole);
B. grafting the short-chain graftable molecule onto the side chain of a cationic polymer backbone molecule (e.g., pp. 28-29, ¶¶208-212: compound C is the graftable molecule to be grafted to the backbone molecule) to obtain a cationic redox polymer containing the transition metal complex medium (Formula 17; ¶99: indicates a general formula of the polymeric transition metal complexes including a polymer backbone and the side group comprising the transition metal) as shown below:
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366
497
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Greyscale
wherein,
M is a transition metal (see Formula 21: Os is the transition metal);
L is a ligand in the transition metal complex that is selected from derivatives of diimidazoles and dipyridines (see Table 1: derivatives of biimidazole and bipyridine); and
x is the length of the hydrocarbon chains on the side chain of the cationic redox polymer molecule (¶93: the polymeric backbone has functional groups; see Formula 21: the spacer L);
y is the length of the hydrocarbon chains on the terminal mercapto alkyl acid molecule (¶96: the transition metal complex precursor includes at least one reactive group; ¶94: the spacer couples the transition metal complex to the polymeric backbone; the spacer includes non-cyclic functional group, e.g., -S-, -C(O)NH-);
z is the length of the hydrocarbon chains on the vinyl nitrogen-containing heterocyclic compound grafted with the transition metal complex (see Formulae 22-24; ¶106: m” is typically in the range of 1 to 18),
wherein the cationic polymer backbone molecule is polylysine (¶93; e.g., Formula 16).
Mao does not disclose 4<x+y+z< 20.
However, Mao teaches the preferred spacer includes a 4 to 30 atom long linear segment having any combination of segments C-C, C-N, and C-S (¶94), which overlaps the claimed range.
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 Mao by adjusting the number of x+y+z within the claimed range because it represents a suitable length of the spacer coupling the polymer backbone and the transition metal complex medium. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05(I). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). MPEP 2144.05(I).
Mao does not disclose the steps of C. dissolving the cationic redox polymer containing the transition metal complex medium obtained in step B in deionized water to obtain an aqueous solution of the cationic redox polymer containing the transition metal complex medium, D. coating a mixed solution of the aqueous solution of the cationic redox polymer containing the transition metal complex medium obtained in step C, and an aqueous solution of glucose oxidase and an aqueous solution of crosslinking agent onto the surface of an electrode, and E. drying the electrode by placing it into a vacuum drying oven after evaporation of the water, to obtain the glucose electrochemical sensor based on the hydrogel of the cationic redox polymer containing the transition metal complex medium.
However, Gregg teaches an amperometric biosensor having on its testing surface a three-dimensional redox polymer network in which peroxidase is immobilized ([Abstract]). The three-dimensional redox polymer network includes a peroxidase enzyme, a cross-linking agent, and a cross-linkable compound (col. 5, ll. 45-46). Mixture of peroxidase and the various polymer components in a common solution is followed by the application of the solution to an electrode surface, using the application including the addition of drops of the solution onto the electrode surface, dip coating, spin coating, or spraying the solution onto the electrode surface. The application step is followed by a curing or setting step, involving drying in air or vacuum (col. 6, ll. 26-34).
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 Mao to dissolving all components, including the redox polymer, transition metal complex medium, and oxidase, and crosslinking agent, to obtain an aqueous solution, which is coated on the electrode surface, and then dried in vacuum as taught by the method of Gregg because it is a well-known technique for fabricating the coating of biosensor electrode. Here, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results. MPEP 2143(I)(A). Further, Mao teaches the use of its transition metal complexes as redox mediators is described in the US Patent 5,320,725 (Gregg) (¶108).
Mao does not disclose wherein the mass ratio of the cationic redox polymer containing the transition metal complex medium, the glucose oxidase and the cross-linking agent in the mixed solution is 1: 5: (0.01-0.5).
However, Gregg teaches the three-dimensional redox polymer network includes an enzyme, a cross-linking agent (e.g., col. 5, line 56: PEGDGE), and a cross-linkable compound (col. 5, ll. 44-46). Gregg teaches an example, using an enzyme HRP (2mg in 100 µL of 0.1M sodium bicarbonate solution; the calculated concentration is 20 mg/mL) and an osmium redox polyamine (10 mg/ml solution) (col. 8, ll. 38-45). The ratio of the enzyme and Polymer I (osmium redox polyamine) varies, such as 1:5, 1:10, 1:50, or 1:100 (col. 8, ll. 47-49). Thus, Gregg teaches the mass ratio of the cationic redox polymer and the enzyme is 1:5. Further, Mao teaches the degree of crosslinking of the redox polymer can influence the transport of electrons or ions and thereby the rates of the electrochemical reactions (Mao, ¶165). Excessive cross-linking of the polymer can reduce the mobility of the segments of the redox polymer (¶165), and inadequate crosslinking of a redox polymer can result in excessive swelling of the redox polymer film and to the leaching of the components of the redox polymer film (¶166), and thus renders the crosslinking degree a result-effective variable.
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 Mao and Gregg by adjusting the mass ratio of the redox polymer and the enzyme as 1:5 as taught by Gregg and adjusting the mass of the cross-linking agent within the claimed range as suggested by Mao because 1:5 is a known ratio for the redox polymer and the enzyme and using such a ratio would yield nothing more than predictable results. MPEP 2143(I)(A). Further, since the amount of the cross-linking agent is a result-effective variable, 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 Mao and Gregg by optimizing the mass ratio of these three components through routine experimentation to achieve a desired crosslinking degree for both mobility and mechanical stability (Mao, ¶¶165-167). MPEP 2144.05 (II)(B).
Regarding claim 12, Mao teaches wherein the transition metal M is osmium (e.g. Formula 1; ¶49).
Regarding claim 13, Mao teaches wherein the ligand L in the transition metal complex is 2,2’-bipyridine (e.g., Table 1, Complex I).
Regarding claim 15, Mao teaches wherein the crosslinking agent is polyethylene glycol diglycidyl ether (¶144: last three lines).
Claim(s) 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mao in view of Gregg, and further in view of Gregg-1 (B.A. Gregg, Redox Polymer Films Containing Enzymes. 1. A Redox-Conducting Epoxy Cement: Synthesis, Characterization, and Electrocatalytic Oxidation of Hydroquinone, J. Phys. Chem. 1991 (95), pp. 5970-75).
Regarding claim 16, Mao and Gregg disclose all limitations of claim 11, but fails to teach wherein the solution mixture in step D is obtained by blending the aqueous solution of the cationic redox polymer containing the transition metal complex medium obtained in step B, the aqueous solution of glucose oxidase and the aqueous solution of crosslinking agent at 0-45°C for 45 minutes to 2 days.
However, Gregg-1 teaches the resulting mixture, including the stock solutions of the redox polymer, POs-EA (Fig. 1: the chemical structure of the osmium-containing redox polymer backbone and the cross-linking agent) and crosslinking agent PEGDE, which is applied to the carbon disk (i.e., electrode) and allowed to dry and set up at 37.5 for 48 h (p. 5971, col. 1, para. 3), which overlaps the claimed ranges of the reaction temperature and time.
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 Mao and Gregg by adjusting the reaction temperature and time within the claimed range as taught by Gregg-1 to obtain the redox polymer containing osmium complex. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05(I). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). MPEP 2144.05(I).
Response to Arguments
Applicant’s arguments have been fully considered but are unpersuasive.
Applicant argues Mao in view of Gregg does not disclose (1) to first graft the spacer groups to the transition metal complex to synthesize a short chain branching molecule, and then graft the resulting short-chain branching molecule onto the side chain of the cationic polymer; (2) the raw materials used for preparing the cationic redox polymer containing the transition metal complex medium; and (3) the ratio of the components in the mixed solution used for coating the electrode (Response, p. 6, last para.).
Applicant relies on Example 6 (¶¶210, 212) to show that Mao first grafts spacer groups to the polymeric backbone and then couples with the transition metal complex (pp. 8-9; p. 11, last para.). This argument is unpersuasive. Examiner notes that compound C (¶208) is firstly synthesized as the short-chain graftable molecule, which contains the transition metal complex (¶208: Os compound A), a nitrogen-containing heterocyclic compound, and an amine terminal group (¶208: compound B; Examiner notes here that the terminal group may be either an amine or a mercapto alkyl acid, as disclosed in ¶¶40-41, and then grafted to the polymer backbone (¶212: compound F).
Applicant argues Mao only generally include the groups -C(O)NH- and C-S, and does not teach these group are preferred groups within the spacers (p. 12, para. 2). This argument is unpersuasive. The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain. A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. MPEP 2123. A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use.
Applicant argues Mao recites an overall spacer segment length, but does not specify the number of carbon atoms within any spacer chain (p. 7, para. 1). This argument is unpersuasive because claim 1 merely recite the overall spacer segment length, i.e., “x+y+z” between 4 and 20.
Applicant argues Gregg fails to disclose the ratios of the components of the solution (p. 13, para. 3). This is unpersuasive because Gregg teaches the ratio of the cationic redox polymer, which is the osmium redox polymer, and the enzyme is 1:5 (Gregg, col. 8, ll. 47-49). Examiner agrees that Gregg does not disclose the ratio of the crosslinking agent with other components. However, Mao teaches the degree of crosslinking of the redox polymer can influence the transport of electrons or ions and thereby the rates of the electrochemical reactions (Mao, ¶165), and must be within a range so that the cross-linking degree would not be excessive to reduce the mobility of the segments of the redox polymer or inadequate to result in excessive swelling of the redox polymer film and the leaching of the components of the redox polymer film (¶¶165-166). Thus, the amount of the cross-linking agent is a result-effective variable that can be optimized through routine experimentation to arrive the claimed subject matter and achieve the desired crosslinking degree for both mobility and mechanical stability. MPEP 2144.05 (II)(B).
Applicant’s Declaration has been considered. The Declarant asserts that Comparative Example 1 employs a redox medium comprising a pyridine ring but lacking a mercapto group between the transition metal complex and the polymer backbone (Declaration, Item 3) which falls within the scope of the chemical structure disclosed in Mao (Item 4). The Declarant seems to refer to Example 3 as disclosed in the present application (Item 1), which seems to implicitly refer to the claimed subject matter in claim 1, and asserts that the glucose electrochemical sensor of the invention exhibit superior interference resistance and more stable signals than the previously disclosed mediator (Item 6). Examiner notes that there are no Comparative Example 1 or Appendix A as described in the Declaration. It seems that Comparative Example 1 refers to the disclosed Example 1 (PGpub Fig. 1; ¶¶38-44), and the claimed example refers to the disclosed Example 3 (Fig. 3; ¶¶51-57). The glucose electrochemical sensor of Example 1 is made from vinylimidazole and 11-mercaptouhndecanoic acid (¶39), and that of Example 3 is made from allyl imidazole and 1-mercaptopropionic acid (¶52). There is no disclosure of a redox medium comprising a pyridine ring but lacking mercapto group. Further, Fig. 1 and 3 are not comparable because Fig. 1 shows the redox curves of the electrode tested with different amount of glucose (Fig. 1; ¶44), while Fig. 3 shows the current curves over time of the electrode with 10 mM of glucose (Fig. 3; ¶57). Thus, Applicant does not provide any evidence or rationale in support for its arguments more than a cursory conclusion.
Conclusion
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/C. SUN/Primary Examiner, Art Unit 1795