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 Objections
Claim(s) 5-7 is/are objected to because of the following informalities:
Claim 5, lines 1-2: “the substituted vinyl monomer” is suggested to be “the first substituted vinyl monomer”
Claim 6, lines 1-2: “the substituted vinyl monomer” is suggested to be “the first substituted vinyl monomer”
Claim 7, lines 1-2: “the substituted vinyl monomer” is suggested to be “the second substituted vinyl monomer”
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(s) 1-22 is/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 pre-AIA the applicant regards as the invention.
Claim 1 recites the limitation
“b) contacting the modified inner surface with an aqueous mixture of a radical initiator and a first substituted vinyl monomer;
c) confining the aqueous mixture to the inner surface of the fused silica capillary;
d) initiating a living radical polymerization by heating or irradiating the aqueous mixture;
e) contacting the modified inner surface with an aqueous mixture of a radical initiator and a second substituted vinyl monomer; and
f) repeating steps c) and d) to form a diblock copolymer.”
It is unclear how the diblock copolymer composed of the first monomer and the second monomer is formed. The specification discloses “a living radical polymerization in the polymer coated separation capillary is reinitiated by repeating steps b) and c) with the second monomer” (PGpub ¶77), wherein the two steps are “b) contacting the modified inner surface with an aqueous mixture of a radical initiator, a substituted vinyl monomer, and an optional second monomer; and c) initiating a living radical polymerization by heating or irradiating the mixture” (¶¶72-73). Thus, the repeated steps are “contacting” and “initiating” steps, not “confining” step. Here, it is unclear for “confining the aqueous mixture to the inner surface of the fused silica capillary” because if the aqueous mixture is contacting the inner surface of a capillary, then the aqueous mixture is deemed to be confined inside the capillary. In light of the specification, it seems that the repeated steps are “contacting” and “initiating” steps that an aqueous mixture of the first and the second monomer is sequentially polymerized.
Further, the limitation “the aqueous mixture” in steps c) and d)” refers to the aqueous mixture of a radical initiator and the first substituted vinyl monomer, and then refers to the aqueous mixture of a radical initiator and the second substituted vinyl monomer after step e) because the repeated steps c) and d) would be confining (or more precisely, contacting) and initiating the aqueous mixture containing the second monomer. Also, it is unclear whether the radical initiator in step b) and in step e) is the same one or not. It is suggested deleting the “repeating steps” and listing out the specific steps.
Claims 2-22 are rejected due to their dependencies or incorporation of claim 1.
Claims 3 and 21 recite the limitation “chemically homogeneous” respectively. It is unclear what chemically homogenous means. Further, the term “homogeneous” is a relative term which renders the claim indefinite because the term is not defined by the claim and the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
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 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claim(s) 1, 3, 5, 7, 18-20, and 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ali (F. Ali, Open tubular capillary electrochromatography with an N-phenylacrylamide-styrene copolymer-based stationary phase for the separation of anomers of glucose and structural isomers of maltotriose, J. Sep. Sci. 2015(38), pp. 1763-70) in view of Huang (U.S. 7,303,821).
Regarding claim 1, Ali teaches a method of fabricating a diblock copolymer-coated separation capillary (Fig. 2; p. 1765, col. 1-2, section 2.2) comprising:
a) contacting the inner surface of a fused silica capillary with a chain transfer reagent (Fig. 2A; p. 1765, col. 1, last line: 4-CPI) to provide a covalently modified inner surface of the fused silica capillary (Fig. 2A: the ligand binding to silanol groups on the inner surface of capillary wall);
b) contacting the modified inner surface with a mixture of a radical initiator (Fig. 2B; p. 1765, col. 2, para. 1: the capillary was the treated with a flow of a solution of sodium diethyl dithiocarbamate in THF);
c) confining the aqueous mixture to the inner surface of the fused silica capillary (Fig. 2B: indicating sodium diethyl dithiocarbamate being confined to the inner capillary wall);
d) initiating a living radical polymerization by heating the aqueous mixture (Fig. 2C: two monomers; p. 1765, col. 2, para. 2: RAFT in situ copolymerization was carried out at 100 ⁰C);
wherein the diblock copolymer-coated separation capillary is thereby fabricated (Fig. 4: inner capillary wall showing thin and compact polymer layer formed on the inner surface of capillary wall as a result of RAFT polymerization).
Ali discloses addition of two monomers for in situ copolymerization (Fig. 2C; p. 1765, col. 2, para. 2) but fails to teach the monomer mixture is an aqueous mixture or contacting the aqueous mixture of a radical initiator and a first substituted vinyl monomer to initiating a living radical polymerization followed by contacting the aqueous mixture of a radical initiator and a second substituted vinyl monomer to initiating a living radical polymerization, i.e., repeating steps c) and d) to form the diblock copolymer after step e).
However, Huang teaches a uniform thin coating comprising of novel block copolymers on the interior wall of the microchannel and capillary columns for electrophoretic separation (Col. 3, lines 16-19). The block copolymer comprises monomers selected from a group consisting of styrene, acrylamide, etc. (Col. 3, lines 21-25), which are substituted vinyl monomer. A coupling agent plays a role of a platform on which a living radical polymerization (col. 4, ll. 37-38). For example, a small bifunctional organic molecule which, at one end, can form covalent bond with functional groups on the support surface, and at the other end, can generate a "living” radical for initiating polymerization of addition monomers (col. 4, ll. 40-43). Therefore, block copolymers can be prepared by the sequential activation of the dormant chain end in the presence of different monomers (col. 8, ll. 19-21), and the polymerization can be reinitiated to extend the chains, or multiblock copolymers can be synthesized by simply switching to a different monomer after each cycle (col. 8, ll. 25-27). Further, the polymerization can be conducted in aqueous or organic solutions (col. 4, ll. 53-54). If the addition monomer is soluble in water, aqueous solution is the most preferred because water is a safe solvent and can reduce the cost (col. 4, ll. 54-56).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Ali by substituting the copolymerization of two monomers by simultaneously initiating the polymerization with the sequential polymerization as taught by Huang so the length of the copolymer chain can be controlled by polymerization time of each step before reinitiating the polymerization to extend the chains by simply switching to a different monomer after each cycle (col. 8, ll. 19-27). Further, it would also have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Ali by conduct polymerization in aqueous solution because water is a safe solvent and can reduce the cost (col. 4, ll. 55-56). 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).
Regarding claim 3, Ali teaches wherein the coating of the diblock copolymer-coated separation capillary is chemically homogeneous (Fig. 4: thin and compact polymer layer).
Regarding claim 5, Ali and Huang disclose all limitations of claim 1, including wherein the molar concentration of the substituted vinyl monomer in the aqueous mixture of step b) has a molar concentration of about 0.1 to about 2 (Huang, col. 12, ll. 10-12: 1.5 M concentration of ethylene glycol methacrylate (EGM) in nanopure water).
Regarding claim 7, Ali and Huang disclose all limitations of claim 1. Huang teaches the molar concentration of one monomer solution, e.g., EGM, is 1.5 M (col. 12, ll. 10-12) and the molar concentration of another monomer solution, e.g., acrylamide, is 7.0 M (col. 11, ll. 48-49). Ali and Huang do not disclose wherein the molar concentration of the substituted vinyl monomer in the aqueous mixture of step e) has a molar concentration of about 0.1 to about 2.
However, Huang teaches one monomer, e.g., EGM, has a molar concentration of 1.5 M (col. 12, ll. 10-12).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Ali and Huang by adjusting the second monomer molar concentration within the claimed range because an overlapping monomer molar concentration is known in the prior art and the monomer molar concentration can be optimized through routine experimentation to. MPEP 2144.05 (II)(B). "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). MPEP 2144.05(II)(A).
Regarding claim 18, the limitation “wherein the diblock copolymer-coated separation capillary, when used for capillary electrophoresis, comprises about 200,000 to about 800,000 theoretical plates” is the intended result of fabricating the claimed diblock-coated separation capillary and does not further limit the method as claimed because it does not require steps to be performed. Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed. In method claims, it is the overall method steps that are given patentable weight not the intended result thereof because the intended result does not materially alter the overall method. Here, this designation is not given patentable weight when it simply expresses the intended result of a process step positively recited. MPEP 2111.04.
Regarding claim 19, the limitation “wherein the diblock copolymer coated separation capillary, when used for capillary electrophoresis, is capable of an electroosmotic flow of about 0.1 x 10-6 cm2 V-1 s-1 to about 10 x 10-6 cm2 V-1 s-1” is directed to the intended result of fabricating the claimed diblock-coated separation capillary and does not further limit the method as claimed because it does not require steps to be performed. Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed. In method claims, it is the overall method steps that are given patentable weight not the intended result thereof because the intended result does not materially alter the overall method. Here, this designation is not given patentable weight when it simply expresses the intended result of a process step positively recited. MPEP 2111.04.
Regarding claim 20, the limitation “wherein the diblock copolymer coated separation capillary, when used for capillary electrophoresis, is capable of performing reproducible separations of at least 5,000 identifiable peptides for at least 100 hours of continuous operation” is directed to the intended result of fabricating the claimed diblock-coated separation capillary and does not further limit the method as claimed because it does not require steps to be performed. Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed. In method claims, it is the overall method steps that are given patentable weight not the intended result thereof because the intended result does not materially alter the overall method. Here, this designation is not given patentable weight when it simply expresses the intended result of a process step positively recited. MPEP 2111.04.
Regarding claim 22, Ali in view of Huang teaches a method (p. 1764, col. 2, last para.: open tubular capillary electrochromatography (OT-CEC); CEC combines the advantageous effects of both CE and HPLC), wherein the method comprises using the diblock copolymer-coated separation capillary fabricated according to claim 1 (as described in claim 1) to separate a mixture of peptides (p. 1764, col. 2, last para.: for the separation of various classes of compounds and bio-molecules such as peptides), but fails to teach the method is for performing capillary electrophoresis.
However, Ali teaches the copolymer-coated OT-CEC column is performed by capillary electrochromatography, which combines the advantageous effects of both CE and HPLC (p. 1764, col. 2, last para.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Ali and Huang by substituting the method of capillary electrochromatography with capillary electrophoresis as suggested because capillary electrochromatography is an alternative method for separation of bio-molecules and the substitution of one known element for another would yield nothing more than predictable results. MPEP 2141(III)(B).
Claim(s) 2 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ali in view of Huang, and further in view of Zhang (B. Zhang, Enzyme-Initiated Reversible Addition-Fragmentation Chain Transfer Polymerization, Macromolecules, 2015(48), page 7792-7802).
Regarding claim 2, Ali and Huang disclose all limitations of claim 1. Ali further teaches using organometallic compound, e.g., dibutyl tin dichloride (DBTDC), as catalyst for attachment of initiator (Fig. 2A; p. 1765, col. 1, para. 1, col. 2, para. 1). Ali and Huang do not teach wherein the aqueous mixture is uncontaminated by metals and free radical scavengers.
However, Zhang teaches an enzyme-initiated reversible addition-fragmentation chain transfer (RAFT) polymerization using biocatalyst, e.g., horseradish peroxidase (HRP) ([Abstract] lines 1-4). The versatility of HRP-initiated RAFT polymerization was demonstrated by controlled polymerization of a wide range of monomers under a variety of conditions, including both homogeneous solution polymerization and heterogeneous dispersion polymerization conditions ([Abstract] lines 9-12), for excellent kinetics, predictable molecular weight, and narrow molecular weight distribution ([Abstract] line 13).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Ali and Huang by substituting the organometallic catalyst with the organic catalyst, HRP, as taught by Zhang because the HRP-initiated RAFT polymerization would provide controllable polymerization for predictable molecular weights and narrow molecular weight distribution ([Abstract] lines 9-10, 13). 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).
Claim(s) 4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ali in view of Huang, and further in view of in view of Liu (Q. Liu, Poly(diallyldimethylammonium chloride) as a Cationic Coating for Capillary Electrophoresis, Journal of Chromatographic Science, 1997 (36), pp. 126-130).
Regarding claim 4, Ali and Huang disclose all limitations of claim 1, but fail to teach wherein the diblock copolymer is positively charged.
However, Liu teaches a novel cationic polymer coating exhibiting a fast anodal EOF by chemically bonded poly(diallyldimethylammonium chloride) onto the interior capillary wall (Abstract). The covalent bonding of cationic groups to the capillary would offer significant advantages to the separation of basic solutes (p. 126, col. 2, last para.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Ali and Huang by substituting the diblock copolymer with one that is positively charged because its cationic groups would offer significant advantages to the separation of basic solutes (p. 126, col. 2, last para.). 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).
Claim(s) 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ali in view of Huang, and further in view of in view of Whitesides (US 2005/0168799).
Regarding claim 6, Ali and Huang disclose all limitations of claim 1. Ali and Huang do not disclose wherein the molar concentration of the substituted vinyl monomer in the aqueous mixture of step e) has a molar concentration of about 0.39 to about 0.56.
However, Whitesides teaches the molecular weight of the polymer chain may be adjusted in polymerization by the incorporation of chain transfer agents into the polymerization mixture, or by adjusting the concentrations of monomer or radical initiator in ways well known in the polymer art (¶213), which renders the monomer concentration a result-effective variable.
Since the eo velocity is equal to the product of the eo mobility and the electric field, thus it follows that the eo velocity may be modulated by changing the magnitude of the electric field ([0032] lines 1-4), rendering the electric field 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 Ali and Huang by adjusting the monomer concentration within the claimed range because the monomer concentration is a result-effective variable and can be optimized through routine experimentation. MPEP 2144.05 (II)(B).
Claim(s) 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ali in view of Huang, and further in view of in view of Rodriguez-Emmenegger (C. Rodriguez-Emmenegger, Low Temperature Aqueous Living/Controlled (RAFT) Polymerization of Carboxybetaine Methacrylamide up to High Molecular Weights, Macromolecular Rapid Communications, 2011(32), pp. 958-965).
Regarding claim 8, Ali and Huang disclose all limitations of claim 1. Ali and Huang do not disclose wherein the molar concentration of the radical initiator in the aqueous mixture of step b) has a molar concentration of about 10-5 to about 10-3.
However, Rodriguez-Emmenegger teaches living/controlled RAFT polymerization up to very high molecular weights of the (3-methacryloylamino-propyl)-(2-carboxy-ethyl)-dimethyl ammonium (carboxybetaine methacrylamide) (CBMAA-3) monomer (p. 959, col. 2, para. 2). All polymerizations were carried out with initiator concentrations of 0.45mM (p. 960, col. 2, para. 1), which is a molar concentration of 4.5 x 10-4 and overlaps the claimed range.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Ali and Huang by adjusting the initiator molar concentration within the claimed range because 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). Further, the monomer molar concentration can be optimized through routine experimentation to. MPEP 2144.05 (II)(B). "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). MPEP 2144.05(II)(A).
Claim(s) 9-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ali in view of Huang, and further in view of in view of Shen (Y. Shen, Effect of Polymerization Method on Structure and Properties of Cationic Polyacrylamide, J. of Appl. Poly. Sci., 2008, 110, page 3889-96), supported by Hiratsuka (U.S. Patent Pub. 2006/0113189) and Data Sheet of MADQUAT (2023) as evidence.
Regarding claims 9-10, Ali and Huang disclose all limitations of claim 1, and wherein the first substituted vinyl monomer and the second vinyl monomer are different (e.g., Ali, p. 1765, col. 2, para. 2: styrene, MAA, N-phenylacarylamide; Huang, col. 13, PEGM/PAAm copolymer), i.e., one substituted vinyl monomer or a block of polyethylene units of the diblock copolymer is i) –C(=O)NR2 wherein R is H (acrylamide monomer is –C(=O)NH2).
Ali and Huang do not disclose another substituted vinyl monomer is ii) –C(=O)O(C1-C6)alkyl-N(Ra)3X wherein each Ra is independently H, (C1-C6)alkyl, or aryl, and is X is a counter ion.
However, Shen teaches acrylamide-based cationic polymers are used in solids/liquid separations (page 3889, Col. 2, para. 1, lines 1-4) including Acrylamide(AM) and 2-(methacryloyloxy)ethyltrimethylammonium chloride (MADQUAT) copolymers (p(AM-MADQUAT)) (page 3889, Col. 2, para. 1, lines 6-9) with an effect on a reduced zeta potential (page 3894, Col. 2, para. 2, lines 6-7). As evidenced by Hiratsuka, by coating the inner wall surface of a separation column using materials with reduced absolute zeta potential value, the electroosmotic flow generated inside the separation column was delayed, thereby improving the separation efficiency (Hiratsuka, [0015] lines 1-5). Thus, the copolymers (p(AM-MADQUAT)) are suitable polymeric coating of separation capillary for reduced zeta potential, delayed EOF, and improved separation efficiency. As evidenced by its data sheet of MADQUAT, its chemical formula is:
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Here, MADQUAT is polyethylene substituted by -C(=O)OCH2CH2N(CH3)3Cl, wherein -CH2CH2- is the (C1-C6) alkyl, C2 alkyl, Ra is CH3, C1 alkyl, and Cl is the counter ion.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Ali and Huang by substituting the polyethylene units substituted by styrene with the MADQUAT substituted polyethylene units as taught by Shen because such a copolymer was also recognized as useful in separations and in reducing zeta potential (Shen, page 3894, Col. 2, para. 2, lines 6-7). The selection of a known material, which is based upon its suitability for the intended use, is within the ambit of one of ordinary skill in the art. MPEP § 2144.07. Here, the combined Ali, Huang, and Shen would necessarily result in the copolymer being a block copolymer p(AM-MADQUAT) with a block of polyethylene units substituted by -C(-O)NH2 and another block of polyethylene units substituted by -C(=O)OCH2CH2N(CH3)3Cl.
Regarding claim 11, Ali, Huang, and Shen disclose all limitations of claim 9, but fail to teach wherein a second block of polyethylene units of the diblock copolymer is substituted by -C(=O)OCH2N(CH3)3X.
However, Shen teaches copolymers (p(AM-MADQUAT), in which pMADQUAT is polyethylene substituted by -C(=O)OCH2CH2N(CH3)3Cl (X=Cl).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Ali, Huang, and Shen by substituting the second block of the diblock copolymer (i.e., pMADQUAT) with the one substituted by -C(=O)OCH2N(CH3)3Cl because MADQUAT and the claimed component have a very close structural similarity, i.e., the C1 alkyl and C2 alkyl, making a prima facie case of obviousness for chemical compounds having very close structural similarities and similar utilities. MPEP 2144.09(I).
Regarding claim 12, Ali, Huang, and Shen disclose all limitations of claim 9. Since Huang teaches the generic structure of a coupling agent is: Z-L-Y, wherein Z is a functional group capable of forming a covalent bond with a functional group on the surface; L is a divalent organic moiety; Y is a functional group capable of generating a living radical for initiating polymerization of addition monomers (Huang, col. 4, ll. 46-59), the combined Ali, Huang, and Shen would resulting in the diblock copolymer comprising one end of a block (e.g., polyethylene units substituted by –C(=O)OCH2N(CH3)3X) directly bonded to a chain transfer moiety (e.g., the support surface or the inner surface of capillary) and the other end of the group is directly bonded to another block (e.g., polyethylene units substituted by –C(=O)NH2).
Further, the sequence of the two blocks connected to the inner surface of the capillary is prima facie obvious because changes in sequence of adding monomers during the living RAFT polymerization for sequential copolymerization of two blocks in the absence of new or unexpected results. MPEP 2144.04(IV)(C).
Claim(s) 13-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ali, Huang, and Shen, and further in view of Rotzoll (R. Rotzoll, I. Controlled Radical Polymerization Trithiocarbonates Containing Trimethoxysilyl Functionalities as Mediating Agents in Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymerization of Methyl Acrylate, Macromol. Symp. 2009, 275-276, page 1–12), and further in view of Rodriguez-Emmenegger.
Regarding claims 13-15, Ali, Huang, and Shen disclose all limitations of claim 1 and all limitations of claim 11 (as described in claim 11). Thus, the modified combination of Ali, Huang, and Shen would result in a diblock copolymer of acrylamide (i.e., -C(=O)NH2 substituted polyethylene units) and -C(=O)OCH2N(CH3)3 substituted polyethylene units and meet the limitations that “X is halo (e.g., Shen: chloride),” “Ra is H,” “n is 2 to 10,000,” “m is 2 to 10,000” and “b indicates that Formula I and/or Formula IA is a diblock copolymer” in claims 14-15, respectively.
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Ali, Huang, and Shen do not explicitly disclose wherein the covalently modified inner surface of the fused silica capillary comprises -SiJ2(CH2)3SC(=S)S-, wherein each J is independently H, OH, -O(C1-C6)alkyl, or halo (claim 13) or wherein J is methoxy (claim 14).
However, Rotzoll teaches using RAFT to produce a block copolymerization of the living anchored pMA chains with styrene (Sty) (Abstract), wherein benzyl(3-trimethoxylsilylpropyl)trithiocarbonate(BTPT) is used as a chain transfer moiety (page 5, Scheme 1: BTPT; here, BTPT has the chain transfer moiety part -O-Si(OCH3)2- and J is -O(C1-C6)alkyl (e.g., methoxy); page 10, Scheme 3). RAFT graft polymerization of MA mediated by anchored BTPT afforded well-defined surface-bound pMA chains (page 12, Col. 1, para. 2, lines 21-22).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Ali, Huang, and Shen by substituting the chain transfer moiety with BTPT as taught by Rotzoll because RAFT graft polymerization of MA mediated by anchored BTPT afforded well-defined surface-bound pMA chains (page 12, Col. 1, para. 2, lines 21-22). 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).
Ali, Huang, and Shen do not explicitly disclose wherein E is cyano (claim 14) or -CN (claim 15).
However, Rodriguez-Emmeneger teaches using water soluble initiator 4,4-azobis(4-cyanopentanoic acid) (V-501) (p. 959, col. 2, para. 3). Since the initiator is the “living” radical for chain extension during RAFT polymerization, the end of the polymer would be the end of the polymer chain (see p. 960, Scheme 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Ali, Huang, and Shen by substituting end group of the diblock copolymer with cyano (CN) as taught by Rodriguez-Emmeneger because it is a known initiator for “living” RAFT polymerization and would result in the end group of the formed polymer. 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).
Regarding claims 16-17, Ali and Huang disclose all limitations of claim 1, and all limitations of claim 11 (as described in claim 11). Thus, the modified combination of Ali, Huang, and Shen would result in a diblock copolymer of acrylamide (i.e., -C(=O)NH2 substituted polyethylene units) and -C(=O)OCH2N(CH3)3 substituted polyethylene units and meet the limitations that “X is halo (e.g., Shen: chloride),” “Ra is H,” “n is 2 to 10,000,” “m is 2 to 10,000” and “b indicates that Formula II and/or Formula IIA is a diblock copolymer” in claims 16-17, respectively.
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Ali, Huang, and Shen do not explicitly disclose wherein the covalently modified inner surface of the fused silica capillary comprises -SiJ2(CH2)3SC(=S)S-, wherein each J is methoxy (claims 16-17).
However, Rotzoll teaches using RAFT to produce a block copolymerization of the living anchored pMA chains with styrene (Sty) (Abstract), wherein benzyl(3-trimethoxylsilylpropyl)trithiocarbonate(BTPT) is used as a chain transfer moiety (page 5, Scheme 1: BTPT; here, BTPT has the chain transfer moiety part -O-Si(OCH3)2- and J is -O(C1-C6)alkyl (e.g., methoxy); page 10, Scheme 3). RAFT graft polymerization of MA mediated by anchored BTPT afforded well-defined surface-bound pMA chains (page 12, Col. 1, para. 2, lines 21-22).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Ali, Huang, and Shen by substituting the chain transfer moiety with BTPT as taught by Rotzoll because RAFT graft polymerization of MA mediated by anchored BTPT afforded well-defined surface-bound pMA chains (page 12, Col. 1, para. 2, lines 21-22). 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).
Ali, Huang, and Shen do not explicitly disclose wherein E is cyano (claim 16) or -CN (claim 17).
However, Rodriguez-Emmeneger teaches using water soluble initiator 4,4-azobis(4-cyanopentanoic acid) (V-501) (p. 959, col. 2, para. 3). Since the initiator is the “living” radical for chain extension during RAFT polymerization, the end of the polymer would be the end of the polymer chain (see p. 960, Scheme 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Ali, Huang, and Shen by substituting end group of the diblock copolymer with cyano (CN) as taught by Rodriguez-Emmeneger because it is a known initiator for “living” RAFT polymerization and would result in the end group of the formed polymer. 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, Examiner notes that the sequence of the two blocks connected to the inner surface of the capillary is prima facie obvious because changes in sequence of adding monomers during the living RAFT polymerization for sequential copolymerization of two blocks in the absence of new or unexpected results. MPEP 2144.04(IV)(C).
Claim(s) 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ali, Huang, and Shen, and further in view of Zhang.
Regarding claim 21, Ali and Huang disclose all limitations of claim 1. Ali and Huang further disclose wherein the diblock copolymer coated separation capillary comprises:
a fused silica capillary (p. 1765, col. 1, para. 2: fused silica capillary); and
a surface-confined aqueous reversible addition-fragment chain transfer (SCARFT) coating (Fig. 2C: the formation of N-phenylacrylamide-styrene copolymer) comprising a chain transfer moiety (Fig. 2A; p. 1765, col. 1, last line: 4-CPI) covalently bonded to the inner surface of the fused silica capillary (Fig. 2A: inner capillary wall);
a substituted polyethylene polymer covalently bonded to the chain transfer moiety of the coating; wherein a block of polyethylene units of the polymer is substituted by:
i) –C(=O)NR2 wherein R is H or (C1-C6)alkyl (e.g., Ali, p. 1765, col. 2, para. 2: styrene, MAA, N-phenylacarylamide; Huang, col. 13, PEGM/PAAm copolymer; i.e., acrylamide monomer is –C(=O)NH2);
wherein the coating is chemically homogeneous (Fig. 4: thin and compact polymer layer).
Ali and Huang do not disclose another block of polyethylene units of the polymer is substituted by: ii) –C(=O)O(C1-C6)alkyl-N(Ra)3X wherein each Ra is independently H, (C1-C6)alkyl, or aryl, and is X is a counter ion.
However, Shen teaches acrylamide-based cationic polymers are used in solids/liquid separations (page 3889, Col. 2, para. 1, lines 1-4) including Acrylamide(AM) and 2-(methacryloyloxy)ethyltrimethylammonium chloride (MADQUAT) copolymers (p(AM-MADQUAT)) (page 3889, Col. 2, para. 1, lines 6-9) with an effect on a reduced zeta potential (page 3894, Col. 2, para. 2, lines 6-7). As evidenced by Hiratsuka, by coating the inner wall surface of a separation column using materials with reduced absolute zeta potential value, the electroosmotic flow generated inside the separation column was delayed, thereby improving the separation efficiency (Hiratsuka, [0015] lines 1-5). Thus, the copolymers (p(AM-MADQUAT)) are suitable polymeric coating of separation capillary for reduced zeta potential, delayed EOF, and improved separation efficiency. As evidenced by its data sheet of MADQUAT, its chemical formula is:
PNG
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280
747
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Greyscale
Here, MADQUAT is polyethylene substituted by -C(=O)OCH2CH2N(CH3)3Cl, wherein -CH2CH2- is the (C1-C6) alkyl, C2 alkyl, Ra is CH3, C1 alkyl, and Cl is the counter ion.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Ali and Huang by substituting the polyethylene units substituted by styrene with the MADQUAT substituted polyethylene units as taught by Shen because such a copolymer was also recognized as useful in separations and in reducing zeta potential (Shen, page 3894, Col. 2, para. 2, lines 6-7). The selection of a known material, which is based upon its suitability for the intended use, is within the ambit of one of ordinary skill in the art. MPEP § 2144.07. Here, the combined Ali, Huang, and Shen would necessarily result in the copolymer being a block copolymer p(AM-MADQUAT) with a block of polyethylene units substituted by -C(=O)NH2 and another block of polyethylene units substituted by -C(=O)OCH2CH2N(CH3)3Cl.
Ali further teaches using organometallic compound, e.g., dibutyl tin dichloride (DBTDC), as catalyst for attachment of initiator (Fig. 2A; p. 1765, col. 1, para. 1, col. 2, para. 1) and fails to teach wherein the aqueous mixture is uncontaminated by metals and free radical scavengers.
However, Zhang teaches an enzyme-initiated reversible addition-fragmentation chain transfer (RAFT) polymerization using biocatalyst, e.g., horseradish peroxidase (HRP) ([Abstract] lines 1-4). The versatility of HRP-initiated RAFT polymerization was demonstrated by controlled polymerization of a wide range of monomers under a variety of conditions, including both homogeneous solution polymerization and heterogeneous dispersion polymerization conditions ([Abstract] lines 9-12), for excellent kinetics, predictable molecular weight, and narrow molecular weight distribution ([Abstract] line 13).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Ali by substituting the organometallic catalyst with the organic catalyst, HRP, as taught by Zhang because the HRP-initiated RAFT polymerization would provide controllable polymerization for predictable molecular weights and narrow molecular weight distribution ([Abstract] lines 9-10, 13). 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).
Conclusion
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/C. SUN/Primary Examiner, Art Unit 1795
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