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 16 is objected to because of the following informalities: in claim 16, line 5, after “a dinitrophenyl label”, a “,” should be added. 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.
Claims 5, 9, 14-16, 18-19 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 5 is vague and indefinite because it is unclear how the linker links only "a portion" of the left-handed PNA. It is unclear what portion of the left-handed PNA is linked with the targeting moiety and how it is linked (covalently or non-covalently, for example).
Claim 5 recites the limitation "the targeting moiety". There is insufficient antecedent basis for this limitation in the claim.
Claim 9 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential structural cooperative relationships of elements, such omission amounting to a gap between the necessary structural connections. See MPEP § 2172.01. The omitted structural cooperative relationships are: it is unclear how the chain of plurality of links is build. It is unclear how said method is performed and what exactly is the chemical structure of said chain.
Claim 14 is vague and indefinite because it is unclear after what steps of the method, the bead is heat melted.
Claim 15 is vague and indefinite because it is unclear of what are the metes and bounds of the limitations provided in the parentheses (nanobody) as the parentheses make it unclear to what part of the claims said limitations apply.
Claim 16 is vague and indefinite because it is unclear of what are the metes and
bounds of the limitations provided in the parentheses (e.g. a metallic label such as gold) as the parentheses make it unclear to what part of the claims said limitations apply. Additionally, the claim is vague and indefinite because the term “e.g.” means “for
example” each time it is used, and therefore it is unclear of what are the metes and
bounds of said term. The addition of “e.g.” to an otherwise definite expression extends
the scope of the expression and therefore renders it indefinite. Further, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Additionally, regarding claim16, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 18 is vague and indefinite because it is unclear of what are the metes and bounds of the term "programmable to allow multiplexing". Is it thru a computer program, or chemical conditions? Is the multiplexing performed on an array? Clarification is needed.
Claim 19 is vague and indefinite because it is unclear of what exactly is "a cyclic modification" and how it is connected to the PNA molecules.
Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 1-4, 6-8, 10-13, 15-17 is/are rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 1-4, 6-12, 14-16 of prior U.S. Patent No.12,071,616 This is a statutory double patenting rejection.
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 5 and 14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 5 and 13 of U.S. Patent No. 12,071,616. Although the claims at issue are not identical, they are not patentably distinct from each other because they both claim identical method comprising wherein the left-handed PNA molecule comprises a linker linking the left-handed PNA molecule to targeting moiety and wherein the surface comprises a surface of a bead and provide a clean capture surface for reuse in further assay.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, 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.
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.
Claim(s) 1-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Carnegie Mellon University US 2015/0197793 A1 (hereinafter 'Carnegie'), in view of Boussaad et al. US 2007/0278111 A 1 (hereinafter 'Boussaad').
Regarding claim 1, Carnegie discloses a method of target enrichment in a sample (para [0014] - "FIG. 2 presents the sequences of PNA and gammaPNA probes and DNA targets."; para [0021] - "formats for using gammaPNA miniprobes for bright fluorescent labeling of nucleic acid, protein, or other targets."; para [0047] - "gammaPNA-2 hybridizes to each of the four model telomeric DNA targets, Telo-1, Telo-2, Telo-3 and Telo-4 having one, two, three and four repeat units respectively with differing affinities. Hybridization of the gammaPNA miniprobe to telomeric DNA was cooperative"), the method comprising the steps of:
introducing a probe comprising a left-handed PNA molecule (para [0008] - "the first and second domains of the gammaPNA probe are covalently attached end-to-end to form a chimeric gammaPNA probe ... the second domain comprises from 4 to 6 left handed PNA monomers"; para [0069] - "domain made exclusively from left-handed PNA monomers.") linked to a capture moiety into a sample comprising target analyte (para [0047] - "gammaPNA-2 hybridizes to each of the four model telomeric DNA targets, Telo-1, Telo-2, Telo-3 and Telo-4 having one, two, three and four repeat units respectively with differing affinities. Hybridization of the gammaPNA miniprobe to telomeric DNA was cooperative");
capturing, with the capture moiety, the target analyte (para [0076] - ''The result will be an overhang of unhybridized PNA residues in the left-handed domain of the first chimeric gammaPNA probe. To capture overhang and label the RNA or a telomeric DNA in a cell sample, one can employ a gammaPNA miniprobe, a fluorophore such as a quantum dot, phycobiliprotein, a DNA nanotag, an antibody, streptavidin, or an enzyme that is functionalized with a gammaPNA"; Note, Instant Applicant Specification pg 3 para 3 - "PNA probes of the invention use capture moieties to bind analyte that is of interest. In some instances, the analyte may be a protein or a surface antigen of a cell. Capture moieties thus may include an antibody or antibody fragment. The antibody or antibody fragment of the capture moiety can be used to capture the antigen associated with analyte of interest."); and
binding the left-handed PNA molecule with a complementary PNA molecule comprising a left-handed chiral structure (para [0067] - "The invention also contemplates chimeric gamma-PNA probes for detecting cellular RNA or DNA, such as telomeric DNA. The chimeric gamma-PNA probes of the invention ... have gamma-PNA monomers of opposite chirality ... The term "chirality" here refers to the ability of one or more gammaPNA monomers to induce ... left-handed twist (helicity) to the gammaPNA helix ... the L-enantiomer will induce lefthanded helical chirality."; para [0029] - "The first and second domains of the inventive chimeric gamma-PNA probe contain PNA monomers of opposing chirality and each domain has at least gamma-PNA monomer ... the second domain has left-handed PNA monomers."), but fails to specifically disclose the complementary PNA molecule being attached to a surface to thereby enrich for target analyte.
Boussaad discloses a PNA (para [0130] - "peptide nucleic acids") attached to a surface to capture target analytes (para [0004] - "a device using peptide nucleic acid receptors, designed to recognize a specific DNA sequence and attached to the surface of silicon nanowires, was able to detect the presence of a DNA sequence"; para [0129] - "peptide nucleic acid (PNA) ... The base sequence of an oligonucleotide probe is complementary to the sequence of the portion of the target nucleic acid molecule to which hybridization is desired. An oligonucleotide probe may also be used to bind to a nucleic acid binding protein.") and further discloses a capture moiety capturing an analyte (para [0155] - "Analyte and Capture Moiety"; para [0156] - "Analytes that are targets may be, for example, chemicals and biomolecules. Preferably, biomolecules are analyte targets of the invention. An analyte may be a nucleic acid that is either DNA"; para [0157] - "The capture moiety binds the analyte when it is present in the test sample. The capture moiety may be any molecule that can bind to an analyte"). Since Boussaad discloses an analyte capture system that comprises a PNA (para [0004] - "a device using peptide nucleic acid receptors, designed to recognize a specific DNA sequence and attached to the surface of silicon nanowires, was able to detect the presence of a DNA sequence"; para [0129] - "peptide nucleic acid (PNA) ... The base sequence of an oligonucleotide probe is complementary to the sequence of the portion of the target nucleic acid molecule to which hybridization is desired. An oligonucleotide probe may also be used to bind to a nucleic acid binding protein."; para [0130]), it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include the left-handed chiral PNA of Carnegie in the surface bound PNA system of Boussaad in order to improve analyte capture and target enrichment for applications thereof.
Regarding claim 2, Carnegie and Boussaad make obvious the method of claim 1, and Boussaad further discloses wherein the surface comprises a bead (para [0164] - "Preferably the capture moiety is on a surface ... Where the surface is a support, the support may be of any shape, including ... a bead, and a tube. A bead may be for example a magnetic bead, a hydrogel bead, a solid bead, a silica coated bead, or other type of bead.").
Regarding claim 3, Carnegie and Boussaad make obvious the method of claim 2, and Boussaad further discloses wherein the bead is a magnetic bead (para [0164] - "Preferably the capture moiety is on a surface ... Where the surface is a support, the support may be of any shape, including ... a bead, and a tube. A bead may be for example a magnetic bead, a hydrogel bead, a solid bead, a silica coated bead, or other type of bead.").
Regarding claim 4, Carnegie and Boussaad make obvious the method of claim 1, and Boussaad further discloses wherein the surface comprises a fixed substrate (para [0161] - "the capture moiety or redox reporter must be affixed to a surface."; para [0164] - "Preferably the capture moiety is on a surface ... Where the surface is a support, the support may be of any shape"; para [0160] - "In several embodiments the invention relies on the presence of a capture moiety to immobilize the analyte on a surface. Generally the capture moiety is affixed on the surface or support.").
Regarding claim 5, Carnegie and Boussaad make obvious the method of claim 1, and Carnegie further discloses wherein the left-handed PNA molecule comprises a linker linking a portion of the left-handed PNA molecule comprising a nucleotide sequence with the targeting moiety (para [0008] - "the first and second domains of the gammaPNA probe are covalently attached end-to-end to form a chimeric gammaPNA probe ... the second domain comprises from 4 to 6 left handed PNA monomers"; para [0069] - "domain made exclusively from left-handed PNA monomers."; para [0014] - "FIG. 2 presents the sequences of PNA and gammaPNA probes and DNA targets."; para [0009] - "attached to the gammaPNA monomer using a linker"; para [0047] - "gammaPNA-2 hybridizes to each of the four model telomeric DNA targets, Telo-1, Telo-2, Telo-3 and Telo-4 having one, two, three and four repeat units respectively with differing affinities. Hybridization of the gammaPNA miniprobe to telomeric DNA was cooperative"; para [0064] - ''The labeling of telomeric DNA according to this methodology is illustrated in Scheme 4, where an alkyne functionalized gammaPNA miniprobe will be permitted to contact an azido dye under mild conditions to form a triazole linked dye-gammaPNA miniprobe product").
Regarding claim 6, Carnegie and Boussaad make obvious the method of claim 1, and Carnegie further discloses wherein the method further includes introducing a second probe into the sample (para [0044] - "The ability of gamma-PNA miniprobes to label telomeres within cells was explored using fixed osteosarcoma cells. For this study, Cy3-labeled gammaPNA-1, a 12-mer, was introduced into fixed cells"), said second probe comprising a left-handed PNA, a targeting moiety, and a detection moiety (para [0008] - "the first and second domains of the gammaPNA probe are covalently attached end-to-end to form a chimeric gammaPNA probe ... the second domain comprises from 4 to 6 left handed PNA monomers"; para [0069] - "domain made exclusively from left-handed PNA monomers."; para [0014] - "FIG. 2 presents the sequences of PNA and gammaPNA probes and DNA targets."; para [0021] - "formats for using gammaPNA miniprobes for bright fluorescent labeling of nucleic acid, protein, or other targets."; para [0035] - "Dyes typically conjugated to the gammaPNA miniprobes or chimeric gammaPNA probes described above are Cy3, Cy5, Cy7, Cy3B, Cy3.5, Cy5.5, coumarin, acridine derivatives, eosin derivatives and fluorescein.").
Regarding claim 7, Carnegie and Boussaad make obvious the method of claim 6, and Carnegie further discloses wherein the targeting moiety is a right-handed targeting PNA (para [0029] - "the inventive chimeric gamma-PNA probe has a first domain having right-handed PNA monomers while the second domain has left-handed PNA monomers. The sequence of the first domain is complementary to the sequence of a target telomere"; para [0068] - "By using both right-handed and left-handed mini-PEG gamma-PNA monomers the present inventors will synthesize a chimeric gammaPNA probe having a right-handed domain and a left-handed domain that are attached to each other end-to end. The right-handed domain will have a sequence that is complementary to the sequence of a target DNA").
Regarding claim 8, Carnegie and Boussaad make obvious a method of claim 1, and Boussaad further discloses wherein the capture moiety comprises an antibody or an antibody fragment (para [0157] - "The capture moiety binds the analyte when it is present in the test sample. The capture moiety may be any molecule that can bind to an analyte ... lf an analyte is a protein, an antibody recognizing an epitope of that protein is a binding partner. If an analyte protein naturally binds to another protein"; para [0128] - "The term "antibody”).
Regarding claim 9, Carnegie and Boussaad make obvious the method of claim 1, and Carnegie further discloses wherein the method includes building a chain with a plurality of links provided by left-handed PNA pairs, and the chain includes some or all of targets, antibodies, and detection moieties (para [0076] - "The result will be an overhang of unhybridized PNA residues in the left-handed domain of the first chimeric gammaPNA probe. To capture overhang and label the RNA or a telomeric DNA in a cell sample, one can employ a gammaPNA miniprobe, a fluorophore such as a quantum dot, phycobiliprotein, a DNA nanotag, an antibody, streptavidin, or an enzyme that is functionalized with a gammaPNA"; para [0008] - "the first and second domains of the gammaPNA probe are covalently attached end-to-end to form a chimeric gammaPNA probe ... the second domain comprises from 4 to 6 left handed PNA monomers"; para [0069] -"domain made exclusively from left-handed PNA monomers."; para [0014] - "FIG. 2 presents the sequences of PNA and gammaPNA probes and DNA targets."; para [0009] - "attached to the gammaPNA monomer using a linker"; para [0047] - "gammaPNA-2 hybridizes to each of the four model telomeric DNA targets, Telo-1, Telo-2, Telo-3 and Telo-4 having one, two, three and four repeat units respectively with differing affinities. Hybridization of the gammaPNA miniprobe to telomeric DNA was cooperative"; para [0064] - ''The labeling of telomeric DNA according to this methodology is illustrated in Scheme 4, where an alkyne functionalized gammaPNA miniprobe will be permitted to contact an azido dye under mild conditions to form a triazole linked dye-gammaPNA miniprobe product").
Regarding claim 10, Carnegie and Boussaad make obvious the method of claim 1, and Carnegie further discloses wherein the method is carried out at a temperature in the range of 18°C to 80°C (para [0081] - "For staining and imaging of chromosome metaphase spreads the cells ... 12 min at 37°C."; para [0082] - ''The chromosomal DNA samples stained with G-clamp gammaPNA 6mer (gammaPNA-3) (FIG. 8) were treated with 500 ug/ml RNAse A (lnvitrogen) at 37°C.").
Regarding claim 11, Carnegie and Boussaad make obvious the method of claim 10, and Carnegie further discloses wherein the method is carried out at a temperature of about 37°C (para [0081] - "For staining and imaging of chromosome metaphase spreads the cells ... 12 min at 37°C."; para [0082] - "The chromosomal DNA samples stained with G-clamp gammaPNA 6mer (gammaPNA-3) (FIG. 8) were treated with 500 ug/ml RNAse A (lnvitrogen) at 37°C.").
Regarding claim 12, Carnegie and Boussaad make obvious the method of claim 1, and Boussaad further discloses wherein the target analyte comprises RNA (para [0156] - "An analyte may be a nucleic acid that is ... any type of RNA, for example ribosomal RNA, messenger RNA, and antisense RNA."; para [0181] - "Upon hybridization of the complementary strand of the analyte DNA (or RNA) to the enzymebound oligonucleotide probe"; para [0224] - "are both complementary to and bridged by the analyte single-stranded DNA/RNA to be detected.").
Regarding claim 13, Carnegie and Boussaad make obvious the method of claim 12, and Boussaad further discloses wherein the RNA comprises 18s ribosomal RNA (para [0156] - "An analyte may be a nucleic acid that is ... any type of RNA, for example ribosomal RNA, messenger RNA, and antisense RNA."; para [0181] - "Upon hybridization of the complementary strand of the analyte DNA (or RNA) to the enzyme-bound oligonucleotide probe"; para [0224] - "are both complementary to and bridged by the analyte single-stranded DNA/RNA to be detected.").
Regarding claim 14, Carnegie and Boussaad make obvious the method of claim 1, and Boussaad further discloses wherein the surface comprises a surface of a bead, and the bead (para [0164] - "Preferably the capture moiety is on a surface ... Where the surface is a support, the support may be of any shape, including ... a bead, and a tube. A bead may be for example a magnetic bead, a hydrogel bead, a solid bead, a silica coated bead, or other type of bead."), but fails to specifically disclose after performing steps of the method, is a heat melted to provide a clean capture surface for reuse in a further assay.
However, Boussaad does disclose including wash steps and various temperature conditions (para [0131] - "A nucleic acid molecule is "hybridizable" to another nucleic acid molecule ... under the appropriate conditions of temperature ... Hybridization and washing conditions are well known ... Post-hybridization washes determine stringency conditions. One set of preferred conditions uses a series of washes starting with 6xSSC, 0.5% SOS at room temperature for 15 min, then repeated with 2xSSC, 0.5% SOS at 45°C. for 30 min"; para [0188] - "Unbound analyte that does not bind to surface attached capture moiety molecules is removed. Likewise, any redox reporter conjugate that is not associated with bound analyte is removed. Removing these unbound molecules may be achieved by washing with an appropriate buffer, as would be known to one skilled in the art.") and Carnegie discloses applying melting conditions to a construct (para [0079] - "Melting curves were recorded by monitoring absorbance at 260 nm with heating/cooling ramps of 1°C./min."). Since it was commonly known in the field of molecular biology that elevated temperatures can be applied to melt a bead, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to apply the compositions and methods of Carnegie and Boussaad, during the course of experimentation, in order to heat melt a bead surface to clean a capture surface and improve assay re-usability.
Regarding claim 15, Carnegie and Boussaad make obvious the method of claim 1, and Boussaad further discloses wherein the capture moiety comprises any one or more of ... a protein, a peptide ... an antibody (para [0157] - "The capture moiety binds the analyte when it is present in the test sample. The capture moiety may be any molecule that can bind to an analyte ... lf an analyte is a protein, an antibody recognizing an epitope of that protein is a binding partner. If an analyte protein naturally binds to another protein"; para [0128] - ''The term "antibody"").
Regarding claim 16, Carnegie and Boussaad make obvious the method of claim 1, and Carnegie further discloses wherein a detection moiety is linked with the left-handed PNA molecule, and the detection moiety includes one or more of the following: a fluorescent label (para [0008] - "the first and second domains of the gammaPNA probe are covalently attached end-to-end to form a chimeric gammaPNA probe ... the second domain comprises from 4 to 6 left handed PNA monomers"; para [0069] - "domain made exclusively from left-handed PNA monomers."; para [0014] - "FIG. 2 presents the sequences of PNA and gammaPNA probes and DNA targets."; para [0021] - "formats for using gammaPNA miniprobes for bright fluorescent labeling of nucleic acid, protein, or other targets."; para [0035] - "Dyes typically conjugated to the gammaPNA miniprobes or chimeric gammaPNA probes described above are Cy3, Cy5, Cy7, Cy3B, Cy3.5, Cy5.5, coumarin, acridine derivatives, eosin derivatives and fluorescein.").
Regarding claim 17, Carnegie and Boussaad make obvious the method of claim 1, and Carnegie further discloses wherein the a lefthanded PNA molecule comprises a linker, and the linker comprises a length of 1 to 120 atoms, and/or has one or some of the elements: C, N, O and/or is in a chain that contains only one or a combination of the following bonds: a single bond, a double bond, a triple bond (para [0009] - "Also, the detectable label can be attached to the gammaPNA monomer using a linker, for example, a -CH2-(O-CH2-CH2)n-X linker where X is selected from the group consisting of -NH2-, -CH=H, -COOH and -N3 and n is an integer from 1 to 10."; para [0076] - "The result will be an overhang of unhybridized PNA residues in the left-handed domain of the first chimeric gammaPNA probe. To capture overhang and label the RNA or a telomeric DNA in a cell sample, one can employ a gammaPNA miniprobe, a fluorophore such as a quantum dot, phycobiliprotein, a DNA nanotag, an antibody, streptavidin, or an enzyme that is functionalized with a gammaPNA"; para [0008] - "the first and second domains of the gammaPNA probe are covalently attached end-to-end to form a chimeric gammaPNA probe ... the second domain comprises from 4 to 6 left handed PNA monomers"; para [0069] - "domain made exclusively from left-handed PNA monomers."; para [0014] - "FIG. 2 presents the sequences of PNA and gammaPNA probes and DNA targets."; para [0009] -"attached to the gammaPNA monomer using a linker''; para [0047] - "gammaPNA-2 hybridizes to each of the four model telomeric DNA targets, Telo-1, Telo-2, Telo-3 and Telo-4 having one, two, three and four repeat units respectively with differing affinities. Hybridization of the gammaPNA mini probe to telomeric DNA was cooperative"; para [0064] - ''The labeling of telomeric DNA according to this methodology is illustrated in Scheme 4, where an alkyne functionalized gammaPNA miniprobe will be permitted to contact an azido dye under mild conditions to form a triazole linked dye-gammaPNA miniprobe product").
Regarding claim 18, Carnegie and Boussaad make obvious the method of claim 1, and Carnegie further discloses wherein the PNA molecules are programmable to allow multiplexing (para [0028] - "A detectable label can be covalently attached to an end PNA monomer or an internal PNA monomer of a single domain or multiple detectable labels, such as fluorescent dyes can be attached within a single domain."; para [0059] - "As described above the multiple labels can be covalently attached to a single domain of the inventive gammaPNA miniprobe, as illustrated in Scheme 2."; para [0069] - "domain made exclusively from left-handed PNA monomers."; para [0014] - "FIG. 2 presents the sequences of PNA and gammaPNA probes and DNA targets."; para [0021] - "formats for using gammaPNA miniprobes for bright fluorescent labeling of nucleic acid, protein, or other targets."; para [0035] - "Dyes typically conjugated to the gammaPNA miniprobes or chimeric gammaPNA probes described above are Cy3, Cy5, Cy7, Cy3B, Cy3.5, Cy5.5, coumarin, acridine derivatives, eosin derivatives and fluorescein.").
Regarding claim 19, Carnegie and Boussaad make obvious the method of claim 1, and Carnegie further discloses wherein the PNA molecules are modified with a cyclic backbone modification that induces a left-handed helical structure (para [0069] - "The right-handed and left-handed domains can be directly attached end-to-end via an amide bond or the two domains are attached using a linker, The category "linker" refers to a (C1-C10) alkylene, a (C3-C14) aryl...residue"; para [0070] - "In the present context, the term "alkylene" refers to divalent alkyl."; para [0036] - ''The term "alkyl" denotes straight, branched chain, or cyclic hydrocarbyl groups"; para [0037] - ''The term "aryl" alone or in combination refers to an aromatic monocyclic or bicyclic ring system").
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEZIA RILEY whose telephone number is (571)272-0786. The examiner can normally be reached 7:30-6:00pm.
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/JEZIA RILEY/Primary Examiner, Art Unit 1681 2 September 2026
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