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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 14 October 2025 has been entered.
Election/Restrictions
Claims 12-14 and 24-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10 November 2023.
Claim Interpretation
Attention is directed to MPEP 904.01 [R-08.2012].
The breadth of the claims in the application should always be carefully noted; that is, the examiner should be fully aware of what the claims do not call for, as well as what they do require. During patent examination, the claims are given the broadest reasonable interpretation consistent with the specification. See In re Morris, 127 F.3d 1048, 44 USPQ2d 1023 (Fed. Cir. 1997). See MPEP § 2111 - § 2116.01 for case law pertinent to claim analysis.
It is noted with particularity that narrowing limitations found in the specification cannot be inferred in the claims where the elements not set forth in the claims are linchpin of patentability. In re Philips Industries v. State Stove & Mfg. Co, Inc., 186 USPQ 458 (CA6 1975). While the claims are to be interpreted in light of the specification, it does not follow that limitations from the specification may be read into the claims. On the contrary, claims must be interpreted as broadly as their terms reasonably allow. See Ex parte Oetiker, 23 USPQ2d 1641 (BPAI, 1992). In added support of this position, attention is directed to MPEP 2111 [R-11.2013], where, citing In re Prater, 415 F.2d 1393, 1404-05, 162 USPQ 541, 550-51 (CCPA 1969), is stated:
The court explained that “reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.” The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.
Additionally, attention is directed to MPEP 2111.01 [R-01.2024], wherein is stated:
II. IT IS IMPROPER TO IMPORT CLAIM LIMITATIONS FROM THE SPECIFICATION
“Though understanding the claim language may be aided by explanations contained in the written description, it is important not to import into a claim limitations that are not part of the claim. For example, a particular embodiment appearing in the written description may not be read into a claim when the claim language is broader than the embodiment.” Superguide Corp. v. DirecTV Enterprises, Inc., 358 F.3d 870, 875, 69 USPQ2d 1865, 1868 (Fed. Cir. 2004).
Attention is also directed to MPEP 2111.02 II [R-07.2022]. As stated herein:
II. PREAMBLE STATEMENTS RECITING PURPOSE OR INTENDED USE
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The claim preamble must be read in the context of the entire claim. The determination of whether preamble recitations are structural limitations or mere statements of purpose or use "can be resolved only on review of the entirety of the [record] to gain an understanding of what the inventors actually invented and intended to encompass by the claim" as drafted without importing "'extraneous' limitations from the specification." Corning Glass Works, 868 F.2d at 1257, 9 USPQ2d at 1966. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020) (The court found that the preamble in one patent’s claim is limiting but is not in a related patent); Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) ("where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation")… (Emphasis added)
Attention is directed to MPEP 2111 [R-10.2019]. As stated therein:
During patent examination, the pending claims must be "given their broadest reasonable interpretation consistent with the specification." The Federal Circuit’s en banc decision in Phillips v. AWH Corp., 415 F.3d 1303, 1316, 75 USPQ2d 1321, 1329 (Fed. Cir. 2005) expressly recognized that the USPTO employs the "broadest reasonable interpretation" standard:
The Patent and Trademark Office ("PTO") determines the scope of claims in patent applications not solely on the basis of the claim language, but upon giving claims their broadest reasonable construction "in light of the specification as it would be interpreted by one of ordinary skill in the art." In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364[, 70 USPQ2d 1827, 1830] (Fed. Cir. 2004). Indeed, the rules of the PTO require that application claims must "conform to the invention as set forth in the remainder of the specification and the terms and phrases used in the claims must find clear support or antecedent basis in the description so that the meaning of the terms in the claims may be ascertainable by reference to the description." 37 CFR 1.75(d)(1). (Emphasis added).
Claim Rejections - 35 USC § 112, (b) / Second Paragraph
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.
Standard for Definiteness.
Attention is directed to MPEP 2171 [R-11.2013]:
Two separate requirements are set forth in 35 U.S.C. 112(b) and pre-AIA 35 U.S.C. 112, second paragraph, namely that:
(A) the claims must set forth the subject matter that the inventor or a joint inventor regards as the invention; and
(B) the claims must particularly point out and distinctly define the metes and bounds of the subject matter to be protected by the patent grant.
The first requirement is a subjective one because it is dependent on what the inventor or a joint inventor for a patent regards as his or her invention. Note that although pre-AIA 35 U.S.C. 112, second paragraph, uses the phrase "which applicant regards as his invention," pre-AIA 37 CFR 1.41(a) provides that a patent is applied for in the name or names of the actual inventor or inventors.
The second requirement is an objective one because it is not dependent on the views of the inventor or any particular individual, but is evaluated in the context of whether the claim is definite — i.e., whether the scope of the claim is clear to a hypothetical person possessing the ordinary level of skill in the pertinent art.
Attention is directed to MPEP 2173.02 I [R-07.2022]:
During prosecution, applicant has an opportunity and a duty to amend ambiguous claims to clearly and precisely define the metes and bounds of the claimed invention. The claim places the public on notice of the scope of the patentee’s right to exclude. See, e.g., Johnson & Johnston Assoc. Inc. v. R.E. Serv. Co., 285 F.3d 1046, 1052, 62 USPQ2d 1225, 1228 (Fed. Cir. 2002) (en banc). As the Federal Circuit stated in Halliburton Energy Servs., Inc. v. M-I LLC, 514 F.3d 1244, 1255, 85 USPQ2d 1654, 1663 (Fed. Cir. 2008):
“We note that the patent drafter is in the best position to resolve the ambiguity in the patent claims, and it is highly desirable that patent examiners demand that applicants do so in appropriate circumstances so that the patent can be amended during prosecution rather than attempting to resolve the ambiguity in litigation.”
***
During examination, after applying the broadest reasonable interpretation to the claim, if the metes and bounds of the claimed invention are not clear, the claim is indefinite and should be rejected. Packard, 751 F.3d at 1310 (“[W]hen the USPTO has initially issued a well-grounded rejection that identifies ways in which language in a claim is ambiguous, vague, incoherent, opaque, or otherwise unclear in describing and defining the claimed invention, and thereafter the applicant fails to provide a satisfactory response, the USPTO can properly reject the claim as failing to meet the statutory requirements of § 112(b).”); Zletz, 893 F.2d at 322, 13 USPQ2d at 1322.
Attention is also directed to MPEP 2173.02 III B, which states in part:
To comply with 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph, applicants are required to make the terms that are used to define the invention clear and precise, so that the metes and bounds of the subject matter that will be protected by the patent grant can be ascertained. See MPEP § 2173.05(a), subsection I. It is important that a person of ordinary skill in the art be able to interpret the metes and bounds of the claims so as to understand how to avoid infringement of the patent that ultimately issues from the application being examined. See MPEP § 2173.02, subsection II (citing Morton Int ’l, Inc. v. Cardinal Chem. Co., 5 F.3d 1464, 1470 (Fed. Cir. 1993)); see also Halliburton Energy Servs., 514 F.3d at 1249, 85 USPQ2d at 1658 (“Otherwise, competitors cannot avoid infringement, defeating the public notice function of patent claims.”). Examiners should bear in mind that “[a]n essential purpose of patent examination is to fashion claims that are precise, clear, correct, and unambiguous. Only in this way can uncertainties of claim scope be removed, as much as possible, during the administrative process.” Zletz, 893 F.2d at 322, 13 USPQ2d at 1322 [Fed. Cir. 1989]. (Emphasis added)
Attention is also directed to MPEP 2173.04 [R-10.2019], which states in part:
A broad claim is not indefinite merely because it encompasses a wide scope of subject matter provided the scope is clearly defined. But a claim is indefinite when the boundaries of the protected subject matter are not clearly delineated and the scope is unclear. For example, a genus claim that covers multiple species is broad, but is not indefinite because of its breadth, which is otherwise clear. But a genus claim that could be interpreted in such a way that it is not clear which species are covered would be indefinite (e.g., because there is more than one reasonable interpretation of what species are included in the claim). (Emphasis added)
Holding and Rationale
Claims 1, 7, 10, 11, 15, and 18-23 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1 and 15 are the only independent claims pending. For convenience they are reproduced below.
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As can be seen in claim 1, step (a)(ii.), “the components of the hybridization solution are contacted with the sample as a single solution or each component of the hybridization solution is contacted separately in any order with the sample.” (Emphasis added) As can be seen above, the “hybridization solution” does not comprise “a capture probe”. If the components are “contacted separately” with the “sample”, then the “hybridization solution” is not created and used. It also stands to reason that the “hybridization composition” is not being formed if the components of what would be a “hybridization composition” are, on an individual basis, brought into contact with the sample.
Claim 1 is also confusing as to just what constitutes “a hybridization composition”. As seen in part (a) a “hybridization composition” is formed by combining “a hybridization solution” and “a capture probe”. However, as can be seen in the last “wherein clause”
wherein the hybridization composition comprises: aa. a sodium salt, wherein the sodium salt is NaCl in a concentration of 37.5 mM to 125 mM; and
bb. a quaternary ammonium salt, wherein the quaternary ammonium salt is tetramethylammonium bromide (TMAB), tetramethylammonium nitrate (TMAN), or tetraethylammonium bromide (TEAB) in a concentration of 0.25 M to 1.25 M.
As can be seen above, the “hybridization composition” as set forth in the last wherein clause does not comprise any probe. Given such, it is less than clear as to how one is to be isolating any poly(A) nucleic acid without any hybridization of a probe to the target- the “single stranded poly(A) nucleic acid stretch of consecutive adenine base residues”. It also stands to reason that one would not be “form[ing] nucleic acid-hybrids between the poly(A) nucleic acids and the capture probe” as there is no probe in the last version of “the hybridization composition”. Perhaps applicant had intended to offer two different versions of a “hybridization solution”.
For purposes of examination the recited concentrations of components of the “hybridization solution” (claim 1, first wherein clause) has been construed as final concentrations with all reactants present. Claim 1 is confusing as to just what concentration(s) of the different components of the “hybridization solution” are allowed to be used when the various components are “contacted separately in any order with the sample”. Similar issues of clarity exist with regard to independent claim 15, step (c), line 7.
Claims 7, 10, 11, and 18-23, which depend from claim 1, fail to overcome each of the above identified issues and are similarly rejected.
Claim 15 is indefinite with respect to what conditions are used to effect hybridization of the poly(A) sequence “to a capture probe”. While claim 15 does identify a “hybridization solution”, it is noted that such is “used for washing”. It is unclear as to what, if anything, is used for hybridization.
Claim 15 is indefinite with respect to just how one is to effect “separating the formed hybrids from the remaining portion of the sample” when the method does not require the use of any means that would allow or result in the isolation of the nucleic acid hybrids formed from any and all other nucleic acids, which can comprise other, non-target double-stranded nucleic acids.
The term “particle” in claims 20 and 21 is a relative term which renders the claims indefinite. The term “particle” is not defined by the claim, 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.
Response to argument
At page 11 of the response of 14 October 2025, hereinafter the response, applicant’s representative traverses the rejection of claims 20 and 21 under 35 USC 112(b) for being indefinite with regard to what constitutes the metes and bounds of a “particle”. As asserted to therein:
The Office alleges that “/t/he term “particle” in claims 20 and 21 is a relative term which renders the claims indefinite” and that that “Claim 23 is indefinite with respect to what constitutes the metes and bounds of “next generation sequencing.” Applicant refers to the arguments presented above regarding the use of MPEP 2145 and the reference to paragraph [0212] of the disclosure. Particles for nucleic acid isolation are well understood by persons having ordinary skill in the art such that the metes and bounds of claims 20 and 21 are clear. Moreover, embodiments of particles are discussed throughout the application.
For convenience, paragraph [0212] of the instant disclosure is reproduced below.
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As evidenced above, “the invention is not limited by the exemplary methods and materials disclosed”. Given such, it is less than clear as to just what does constitute the metes and bounds of “particles”.
While it has been asserted that “Particles for nucleic acid isolation are well understood by persons having ordinary skill in the art…” such has not been found persuasive. Attention is directed to MPEP 2145 I [R-01.2024].
An argument by the applicant is not evidence unless it is an admission, in which case, an examiner may use the admission in making a rejection. See MPEP § 2129 and § 2144.03 for a discussion of admissions as prior art.
Arguments presented by applicant cannot take the place of evidence in the record. See In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984); In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997) ("An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case of obviousness."). See MPEP § 716.01(c) for examples of applicant statements which are not evidence and which must be supported by an appropriate affidavit or declaration.
A review of the response fails to find where any affidavit or declaration has been provided.
In view of the above analysis and in the absence of convincing evidence to the contrary, the rejection is maintained.
In view of the above analysis and in the absence of convincing evidence to the contrary, claims 1, 7, 10, 11, 15, and 18-23 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as 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 (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.
Standard for Obviousness.
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 pre-AIA 35 U.S.C. 103(a) 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.
Attention is directed to In re Jung, 98 USPQ2d 1174, 1178 (Fed. Cir. 2011) wherein is stated:
There has never been a requirement for an examiner to make an on-the-record claim construction of every term in every rejected claim and to explain every possible difference between the prior art and the claimed invention in order to make out a prima facie rejection. This court declines to create such a burdensome and unnecessary requirement. “[Section 132] does not mandate that in order to establish prima facie anticipation, the PTO must explicitly preempt every possible response to a section 102 rejection. Section 132 merely ensures that an applicant at least be informed of the broad statutory basis for the rejection of his claims, so that he may determine what the issues are on which he can or should produce evidence.” Chester, 906 F.2d at 1578 (internal citation omitted). As discussed above, all that is required of the office to meet its prima facie burden of production is to set forth the statutory basis of the rejection and the reference or references relied upon in a sufficiently articulate and informative manner as to meet the notice requirement of § 132. As the statute itself instructs, the examiner must “notify the applicant,” “stating the reasons for such rejection,” “together with such information and references as may be useful in judging the propriety of continuing prosecution of his application.” 35 U.S.C. § 132.
Attention is directed to the decision in KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007):
When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill in the art has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
It is further noted that prior art is not limited to the four corners of the documentary prior art being applied. Prior art includes both the specialized understanding of one of ordinary skill in the art, and the common understanding of the layman. It includes “background knowledge possessed by a person having ordinary skill in the art. . . [A] court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR at 1396.
Suggestion, teaching or motivation does not have to be explicit and “may be found in any number of sources, including common knowledge, the prior art as a whole or the nature of the problem itself’” Pfizer, Inc. v. Apotex, Inc. 480 F.3d 1348, 82 USPQ2d 1321 (Fed. Cir. 2007) citing Dystar Textilfarben GMBH v. C. H. Patrick Co., 464 F.3d 1356 (Fed. Cir. 2006).
Holding and Rationale
Claim(s) 1, 7, 10, 11, 15, and 18-23 are rejected under 35 U.S.C. 103 as being unpatentable over Satterfield et al. (2007) (Satterfield et al., Microfluidic Purification and Preconcentration of mRNA by Flow-Through Polymeric Monolith, Anal Chem., 2007 Aug 15;79(16):6230-5.doi: 10.1021/ac0709201. Epub 2007 Jul 11.) in view of Gogos et al. (1990) (Gogos et al. Detection of single base mismatches of thymine and cytosine residues by potassium permanganate and hydroxylamine in the presence of tetralkylammonium salts, Nucleic Acids Res., 1990 Dec 11;18(23):6807-14. doi: 10.1093/nar/18.23.6807).
Satterfield et al. (2007) teach “Efficient and rapid isolation of mRNA is important in the field of genomics as well as in the clinical and pharmaceutical arena. We have developed UV-initiated methacrylate-based porous polymer monoliths (PPM) for microfluidic trapping and concentration of eukaryotic mRNA. PPM are cast-to-shape and are tunable for functionalization using a variety of amine-terminated molecules. Efficient isolation of eukaryotic mRNA from total RNA was first mathematically modeled and then achieved using PPM in capillaries. Purification protocols using oligo dT's, locked nucleic acid substituted dT's, and tetramethylammonium chloride (TMAC) salts were characterized. mRNA yield and purity were compared with mRNA isolated by commercial kits with statistically equivalent yields and purities (determined by qPCR ratio of 18s rRNA and Gusb mRNA markers). Even after extracting 16 microg of mRNA from 315 microg of total RNA, the 0.4-microL volume monolith showed no signs of saturation. Elution volumes were below 20 microL with concentrations up to 1 microg/microL. In addition, the polymeric material exhibited exceptional stability in a range of conditions (pH, temperature, dryness) and was stable for a period of months. All of these characteristics make porous polymer monoliths good candidates for potential microfluidic sample preconcentrators and purifiers (see Abstract).
Satterfield et al. (2007), at page 6230, right column, first paragraph, teach:
[mRNA] is typically extracted from eukaryotic cells via its polyadenosine tail (poly-A); mRNA extraction is based on the interactions between a sequence of polythymine deoxyribonucleotides (oligo dT’s) and the poly-A tail of mRNA. The use of functionalized cellulose to selectively extract polynucleotides was developed early in the 1960s.6-9 The integration of oligo dT’s, specifically for the purpose of mRNA purification, with cellulose columns, cellulose powders, polymeric beads, and magnetic beads was an innovation that followed. (Emphasis added)
Satterfield et al. (2007) further teach that “Several other purification methods were used also, each with three capillaries. Mixed LNA-dT, 100% LNA substituted dT, and oligo dT capillaries were functionalized and then blocked with 1% propylamine in 2-propanol at 90 °C for 15 min. Capillaries were flushed with 100 mL of 10 mM Tris-HCl buffer with 180 mM NaCl and 0.1% SDS. mRNA was bound to mixed LNA-dT columns in 10 mM Tris-HCl buffer with 180 mM NaCl and 0.1% SDS at 45 °C and was washed in 50 mM NaCl in 10 mM Tris-HCl buffer at 45°C. mRNA was eluted at 90 °C in diH2O. mRNA was bound to 100% LNA substituted dT columns with 10 mM Tris-HCl buffer with 180 mM NaCl and 0.1% SDS at 45 °C and was washed in diH2O at 0 °C. mRNA was eluted at 90 °C in diH2O. mRNA was bound to oligo-dT columns in 10 mM Tris-HCl buffer with 180 mM TMAC and 0.1% SDS at 45 °C and was washed in 10 mM Tris-HCl buffer in 3 M TMAC at room temperature (24 °C). A second wash step of 30 mL over 6 min was performed at 90 °C in 10 mM Tris-HCl buffer in 2 M TMAC. After flushing out salt solutions with air, mRNA was eluted at 90 °C in diH2O (See mRNA Purification, 6232).
With regard to the concentration tetramethylammonium chloride (TMAC) salts in hybridization, Gogos et al. (1990) teaches “The interactions of tetralkylarnmonium salts with nucleic acids have been studied for a number of years. Their cations have several interesting chemical properties: preferential binding to AT base pairs, hydrophobic side groups and high molecular weight resulting in low screening of the phosphate charges in DNA. These properties have been exploited in hybridization reactions, to abolish the preferential melting of AT versus GC base pairs, greatly facilitating hybridization studies with oligonucleotide probes. We have found that tetramethylammonium chloride (Me4NCl) accentuates the reactivity of T mismatches (and to a lesser degree C mismatches) towards potassium permanganate, a chemical much less hazardous and unstable than osmium tetroxide. Similarly, tetraethylammonium chloride (Et4NCl) can accentuate the reactivity of C mismatches towards hydroxylamine. We have also demonstrated that these reactions can be made compatible with the recently introduced Hybond M-G (Amersham) chemically modified paper. Thus, we propose tetraalkylammonium enhanced chemical modification on solid support as a very convenient method for detection of point mutations and polymorphisms (See right column, page 6807).
Gogos et al. (1990) further teaches that “When the DNA was immobilized on Hybond M-G, the reaction started by immersing the paper, still wet from the previous annealing step, in 250 ?I of 3M Me4NCl inside a 500 ml Eppendorf tube and then adding 250 ml of 0.2 mM KMnO4/3M Me4NCI (see above). The reaction was left to proceed for 30 min at 20°C and then the solution was replaced with freshly prepared one and left to proceed for another 30 min. The reaction was stopped by simply removing the paper and rinsing it with double distilled water. After another round of rinsing and dehydration in ethanol, the paper was immersed in l M piperidine (100 ml) and incubated as described below. It is important that the paper remains wet after the annealing step, since drying immobilizes the probe and causes increased intensity of background bands (see left column, page 6809).
In view of the above presentation it was well known in the art at the time of the invention to isolate poly(A) nucleic acids, e.g., mRNA through the use of the very same chemicals for the same purpose. In view of such disclosures and in the absence of convincing evidence to the contrary, claims 1, 7, 10, 11, 15, and 18-23 are rejected under 35 U.S.C. 103 as being unpatentable over Satterfield et al. (2007) (Satterfield et al., Microfluidic Purification and Preconcentration of mRNA by Flow-Through Polymeric Monolith, Anal Chem., 2007 Aug 15;79(16):6230-5.doi: 10.1021/ac0709201. Epub 2007 Jul 11.) in view of Gogos et al. (1990) (Gogos et al. Detection of single base mismatches of thymine and cytosine residues by potassium permanganate and hydroxylamine in the presence of tetralkylammonium salts, Nucleic Acids Res., 1990 Dec 11;18(23):6807-14. doi: 10.1093/nar/18.23.6807).
Conclusion
Objections and/or rejections which appeared in the prior Office action and which have not been repeated hereinabove have been withdrawn.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Bradley L. Sisson whose telephone number is (571)272-0751. The examiner can normally be reached Monday to Thursday, from 6:30 AM to 5 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Shen can be reached at 571-272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Bradley L. Sisson/Primary Examiner, Art Unit 1682