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 .
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.
Response to Amendment
The amendment filed January 5, 2026 has been entered. Claims 1, 12-13, 24, 26, and 29 have been amended and claims 4, 9, 18-23, 27-28, and 31-32 are cancelled. Applicant’s amendments have overcome objections to the claims and specification, and the 112(b) rejections and the 103 rejections over Swaminathan, Swaminathan and Liu, Swaminathan and Paudyal, and Swaminathan and Ueno previously set forth in the Non-Final Office Action mailed October 6, 2025. As such, these rejections and objections are hereby withdrawn. This application is the U.S. national phase of International Application No. PCT/US2021/027397, filed on April 15, 2021, which claims the benefit of United States Provisional Patent Application No. 63/011,398, filed April 17, 2020.
Applicant’s arguments filed January 5, 2026 were fully considered but they were not persuasive. Modified/new rejections necessitated by applicants amendment and response to arguments are addressed below.
Claims 1-3, 5-8, 10-17, 24-26, and 29-30 are pending in this application.
Claim Interpretation
Regarding claims 1 and 3: Claim 1 recites inter alia “An oligomer comprising (a) from about 8 to about 25 monomer units of formula (I)…. (b) from 0 to about 24 monomer units of formula (II)….”. Claim 3 recites inter alia, “….wherein the oligonucleotide comprises a sum of from about 12 to about 25 monomer units of formula (I) and formula (II).”. Given that formula (II) can be 0, claim 3 also includes oligomers wherein the sum is based upon the addition of “0” monomer units of formula (II). For example, 12 units of formula (I) plus 0 units of formula (II) equals a sum of 12 monomer units of formula (I) and formula (II).
New Claim Rejections - 35 USC § 112 (d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 6 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Regarding claim 6: Claim 6, which depends from claim 1, recites “wherein the monomer 6. unit of formula (I) has two chiral carbon atoms, wherein the two chiral carbon atoms of at least one monomer unit of formula (I) have an (R,R) configuration or an (S,S) configuration.”. However, claim 1 already recites “monomer units of formula (I):
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wherein the substituents on the tetrahydrofuranyl group have a trans configuration”, which encompasses both R,R and S,S configurations of the monomer unit. Additionally the phrase “at least one” implies that others do not have the configuration that is required to be present as recited by instant claim 1. Thus, claim 6 fails to limit claim 1 with respect the trans configuration and also expands claim 1 by implying, by way of recitation, that such a configuration is not necessarily required by claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Modified 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.
Claims 1-3, 5-8, 10, 16-17, 25-26, and 29-30 are rejected under 35 U.S.C. 103 as being unpatentable over Swaminathan (WO 93/24507, cited in previous action) in view of Pokorski (J. Am. Chem. Soc., 2004, IDS filed October 13, 2022) as evidenced by Fieldhouse (WO 2015/055994, cited in previous action).
Regarding claims 1-3, 5-6, 10, 16-17: Swaminathan teaches oligomers which comprise the presence of one or more nucleomonomers exemplified by formula (V):
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where B is a purine or pyrimidine base or an analogous form thereof; X1 is S, O, SO, SO2, CH2, CHF, CF2, NR or CH lower alkyl including CH-methyl, CH-ethyl, CH-propyl and CH-butyl, provided that adjacent X1 are not both O(pg. 13, lines 16-19, pg. 14, lines 20-25, pg. 15, lines 1-13, drawings pg. 14, figure 8). Although X1 can be selected from multiple options, a specific claim of the reference recites that in formula (V) X is O (pg. 52, lines 1-2, claim 6). Thus, a person of ordinary skill would be drawn to select O from the list of possible alternatives, leading to an oligomer represented by formula (I) as recited by instant claim 1. Pyrimidines include uracil and cytosine and purines include adenine and guanine, as well as analogs thereof (pg. 21, lines 12-21). Swaminathan teaches oligomers containing 2 to 30 nucleomonomers are preferred (pg. 16, lines 16-17). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists (See MPEP 2144.05 (I)). All monomers that are used for incorporation into oligomers are protected at the amino terminus using groups commonly employed in peptide synthesis methods, such as t-butylcarbamates (tBOC) and FMOC (pg. 33, lines 18-21). Terminal oligomer moieties such.as -NH2 or -COOH can be blocked or derivatized using standard procedures of routine use (i.e. amino terminus and carboxy terminus, wherein amino terminus is -NH2 and carboxy terminus is -COOH, as recited by instant claims 10 and 16, pg. 31, lines 12-14). The oligomers of the invention are for binding to complementary nucleic acid target sequences (as recited by instant claim 17, pg. 12, lines 1-8). Swaminathan is directed towards the use of constrained nucleomonomers that are able to bind to a target nucleic acid in a sequence specific manner (pg. 2, lines 15-21).
Swaminathan does not teach the specific stereochemistry (S,S) as recited by instant claim 6.
However, Pokorski teaches that oligomers comprising (S,S)-trans cyclopentyl units significantly increases binding affinity and sequence specificity to complementary DNA (abstract). Pokorski teaches that the (S,S) stereochemistry is more compatible than (R,R) in PNA-DNA duplexes (pg. 15073, col. 1, para. 2). Pokorski teaches both ring size and stereochemistry must restrict the PNA to access only the range of dihedral angles necessary for binding, while excluding conformations that are irrelevant to duplex formation (pg. 15073, col. 1, para. 2).
Taken together, it would have been prima facie obvious to a person of ordinary skill in the art to modify the oligomer of Swaminathan by (3S,4S)-trans stereochemistry into the constrained backbone as taught by Pokorski. A person of ordinary skill in the art would have the motivation to do so with a reasonable expectation of success given that the art establishes the trans configuration is preferred in 5 membered rings in these types of oligomers, in order to improve the ability to bind to DNA sequences.
Regarding claims 7-8: As discussed above, Swaminathan renders obvious the oligomer of instant claim 1. Swaminathan teaches oligomers containing 2 to 30 nucleomonomers are preferred (pg. 16, lines 16-17). Swaminathan further teaches cyclopentyl backbones are contemplated as an alternative in the oligomer (drawings pg. 19, figure 13). Swaminathan suggests the oligomer can comprise one or more invention nucleomonomers disclosed (pg. 13, lines 16-19). Swaminathan directly compares the spatial comparison of an amide linked oligomer with an amide linked oligomer composed of linked cyclopentyl monomers (pg. 19, lines 33-35, drawings pg. 19, figure 13).
Swaminathan does not explicitly teach an oligomer comprising cyclopentyl and tetrahydrofuran backbones as recited by instant claims 7-8.
However, Pokorski teaches that oligomers comprising one or more nucleomonomers, such as the inclusion of cyclopentyl, is a known practice in the art (pg. 15068, top of page, figure 1,). Pokorski teaches that combinations of monomers can impact the stability of the oligomers or modulate binding affinity (pg. 15068, col. 1).
Taken together it would have been prima facie obvious to a person of ordinary skill in the art to modify the oligomer of Swaminathan by incorporating different backbone monomers into the oligomer, such as cyclopentyl (i.e. formula (III) as recited by instant claims 7-8), as taught by Pokorski. A person of ordinary skill in the art would have the motivation to do so with a reasonable expectation of success given that the art establishes mixed oligomers are known in the art, and incorporation of constrained monomers, or other monomers can modulate binding affinity and stability. A person of ordinary skill in the art would be capable of determining the appropriate amount of individual monomers in the oligomer through routine optimization, as the art establishes that by substituting monomers, stability and sequence specificity can be modulated (See MPEP 2144.05 (II)).
Regarding claim 25: Swaminathan teaches, for therapeutic applications, the oligomer active ingredient is generally combined with a carrier such as a diluent or excipient (pg. 42, lines 4-13)
Regarding claims 26 and 29-30: As discussed above Swaminathan and Pokorski render obvious the oligomer of instant claim 6 with trans stereochemistry.
Swaminathan further teaches the synthetic scheme for preparing a monomer corresponding to formula (V) (pg. 33, lines 7-16). Swaminathan teaches synthesis of the monomer described above in figure 8, would be conducted in a manner analogous to the synthetic schemes shown in figures 5 and 6, with synthesis of compounds analogous to compound 26 starting from protected, substituted ethylene diamine having the ring constraints corresponding to those shown in Formulas V (pg. 33, lines 10-16). Figure 5 is directed towards the synthesis of a hydroxymethyl monomer:
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wherein the hydroxymethyl group is protected with a silicon group(pg. 19, lines 12-13, drawings pgs. 8-9, figures 5.1-5.2, drawings pg. 9, compound 26). Replacing the hydroxymethyl ethylene diamine with the appropriate ethylene diamine group as suggested by Swaminathan would lead to the following monomer structure:
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wherein R1 is Fmoc (a nitrogen protecting group), R2 is H, and B is thymine (a nucleobase) (with appropriate stereochemistry as suggested by Pokorski, rendering obvious the compounds of claims 29-30). Additionally, as discussed previously, Swaminathan teaches monomers that are used for incorporation into oligomers are protected at the amino terminus using groups commonly employed in peptide synthesis methods, such as t-butylcarbamates (tBOC) and FMOC (pg. 33, lines 18-21). Thus, R1 can alternatively be a tert-butylcarbamate. Fieldhouse demonstrates that the appropriate trans (3S,4S) tBOC diethylene diamine reagent is known in the prior art:
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(pg. 74, col. 2, top of page, pg. 75, col. 1, para. 0660). With respect to instant claim 26 which can be a considered a precursor the compounds represented by instant claims 29-30, Swaminathan teaches that compound 26 discussed above is synthesized in part utilizing the following reaction:
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(drawings pg. 8, figure 5.1, bottom of page). Similarly, replacing the hydroxymethyl ethylene diamine with the appropriate ethylene diamine group as suggested by Swaminathan would lead to the following precursor monomer structure:
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wherein R1 is Cbz (a nitrogen protecting group), and R2 is ethyl (a c2alkyl), rendering obvious the compound of claim 26.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Swaminathan (WO 93/24507, cited in previous action), Pokorski (J. Am. Chem. Soc., 2004, IDS filed October 13, 2022), and Fieldhouse (WO 2015/055994, cited in previous action) as applied to claims 1-3, 5-8, 10, 16-17, 25-26, and 29-30 above in view of Liu (WO 2010/027326, cited in previous action).
Regarding claim 11: As discussed above, Swaminathan, Pokorski, and Fieldhouse render obvious the oligomer with appropriate stereochemistry an amino terminus as recited by instant claims 1, 6, and 10. Swaminathan teaches the oligomers of the invention can be used as diagnostic reagents to detect the presence or absence of the target nucleic acid sequences to which they specifically bind (pg. 43, lines 23-26). The enhanced binding affinity of the invention oligomers is an advantage for their use as primers and probes (pg. 43, lines 26-28). Diagnostic tests can be conducted by hybridization through either double or triple helix formation which is then detected by conventional means (pg. 43, lines 29-31). For example, the oligomers can be labeled using radioactive, fluorescent, or chromogenic labels and the presence of label bound to solid support detected (pg. 43, lines 31-34). Swaminathan teaches that the amino terminus is suitable for coupling to a label, such as a radioisotope, enzyme, or chromophore (pg. 16, lines 20-28). Swaminathan directly compares the spatial comparison of an amide linked oligomer with an amide linked oligomer composed of linked cyclopentyl monomers (pg. 19, lines 33-35, drawings pg. 19, figure 13).
Swaminathan does not teach wherein the oligomer comprises the dye fluorescein at the amino terminus as recited by instant claim 11.
However, Liu teaches the preparation of peptide nucleic acid molecules comprising peptide acid monomers with a terminal amine group (abstract). Liu teaches the peptide nucleic acid molecules can effectively by labeled by fluorescein at the N-terminus for cellular uptake studies (pg. 39, para. 0123).
Taken together, it would have been prima facie obvious to a person of ordinary skill in the art to modify the oligomer of Swaminathan by conjugating the amino terminus to the dye fluorescein as taught by Liu. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as the art establishes this as a known modification of these types of oligomers for the purpose of performing cellular uptake studies in establishing oligomer uptake. It is prima facie obvious to apply a known technique to a known device (method, or product) ready for improvement to yield predictable results (See MPEP 2143 (ID)).
Claims 12-13 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Swaminathan (WO 93/24507, cited in previous action), Pokorski (J. Am. Chem. Soc., 2004, IDS filed October 13, 2022), and Fieldhouse (WO 2015/055994, cited in previous action) as applied to claims 1-3, 5-8, 10, 16-17, 25-26, and 29-30 above in view of Paudyal (Nucl. Med. Biol., 2013, cited in previous action).
Regarding claims 12-13 and 15: As discussed above, Swaminathan, Pokorski, and Fieldhouse render obvious the oligomer with appropriate stereochemistry an amino terminus as recited by instant claims 1, 6, and 10. Swaminathan teaches the oligomers of the invention can be used as diagnostic reagents to detect the presence or absence of the target nucleic acid sequences to which they specifically bind (pg. 43, lines 23-26). The enhanced binding affinity of the invention oligomers is an advantage for their use as primers and probes (pg. 43, lines 26-28). Diagnostic tests cab be conducted by hybridization through either double or triple helix formation which is then detected by conventional means (pg. 43, lines 29-31). For example, the oligomers can be labeled using radioactive, fluorescent, or chromogenic labels and the presence of label bound to solid support detected (pg. 43, lines 31-34). Swaminathan teaches that the amino terminus is suitable for coupling to a label, such as a radioisotope, enzyme, or chromophore (pg. 16, lines 20-28).
Swaminathan does not teach wherein the oligomer comprises 1,4,7,10-tetraazacyclododecane-N, N’, N”, N”’-tetraacetic acid (DOTA) in combination with 64Cu at the amino terminus with a linker comprising
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wherein m is 2 as recited by instant claim 12-13 and 15.
However, Paudyal teaches a method for monitoring breast cancer therapy by determining HER2 mRNA in malignant breast cancer cells with positron emission tomography (abstract). Paudyal teaches the synthesis of a radionuclide-chelator-peptide nucleic acid-peptide agents comprising a Cu-64-DOTA as the radiolabel-chelator with a
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linker, wherein m is 2, conjugated to a peptide nucleic acid (PNA) at the amino terminus (pg. 2, introduction, paras. 4, pg. 13, scheme 1). The conjugate has the following structure
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(pg. 13, scheme 1).
Taken together, it would have been prima facie obvious to a person of ordinary skill in the art to modify the oligomer of Swaminathan by conjugating the amino terminus to a radiolabel as demonstrated by Paudyal. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as the art establishes this as a known modification of these types of oligomers for the purpose of acting as hybridizing diagnostic agents as suggested by Swaminathan and taught by Paudyal. It is prima facie obvious to use a known technique to improve similar devices (methods, or products) in the same way (See MPEP 2143 (IC)).
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Swaminathan (WO 93/24507, cited in previous action), Pokorski (J. Am. Chem. Soc., 2004, IDS filed October 13, 2022), and Fieldhouse (WO 2015/055994, cited in previous action) as applied to claims 1-3, 5-8, 10, 16-17, 25-26, and 29-30 above in view of Gildea (US 6,326,479, cited in previous action).
Regarding claim 14: As discussed above, Swaminathan, Pokorski, and Fieldhouse render obvious the oligomer with appropriate stereochemistry an amino terminus as recited by instant claims 1, 6, and 10. Swaminathan teaches oligomers of any length may be prepared including 10-mers (10 nucleomonomers), 20-mers, 50-mers, 100-mers, 200-mers, 500-mers or oligomers of greater length (pg. 16, lines 13-16). Swaminathan teaches oligomers containing 2 to 30 nucleomonomers are preferred (pg. 16, lines 16-17). Swaminathan teaches oligomers are two or more nucleomonomers covalently coupled to each other by a linkage or substitute linkage moiety (i.e. a linker, pg. 23, lines 22-24). Thus, an oligomer can have as few as two covalently linked nucleomonomers (a dimer) (i.e. a linker, pg. 23, lines 24-26).
They do not explicitly teach wherein the oligomer is a conjugated through the amino terminus with a second oligomer comprising about 12 to about 25 monomer units of formula (I).
However, Gildea teaches methods for modulating the aqueous solubility of peptide nucleic acid (PNA) polymers (abstract). Gildea teaches for most applications an oligomer of 12-15 is optimal (col. 2, lines 58-59). Longer PNA oligomers, depending on the sequence, tend to aggregate and are difficult to purify and characterize (col. 2, lines 59-61). A number of modifications have been made to peptide nucleic acids in order to improve their aqueous solubility or minimize polymer self-aggregation, which include modification of the backbone (col. 3, lines 10-12, 17-20). For example, a PNA may be modified by condensation of a suitable carboxylic acid moiety with the N-terminus or side chain nucleophilic group ( e.g. amine, hydroxyl or thiol) of the polymer during chemical assembly (col. 16, lines 56-60). Alternatively, if polymer assembly is to be continued after N-terminal modification or labeling, typically a suitably protected amino acid synthon is used so that the amino group of this synthon can be used to further extend the polymer (col. 16, lines 61-65). Gildea teaches the use of branched protected amino acid synthons (i.e. a linker) which can be incorporated at any position of the polymer sequence without terminating polymer assembly in order to enhance solubility and reduce polymer aggregation (col. 17, lines 3-12). When modifying PNAs it is preferable to use suitably protected amino acids which will maintain the spacing between nucleobases (col. 29, lines 38-40). Preferred modifying moieties can be inserted within the polymer without disrupting the nucleobase spacing and thereby, presumably, not alter the hybridization efficiency of the oligomer to a target nucleic acid (col. 29, lines 40-43).
Taken together it would have been prima facie obvious to a person of ordinary skill in the art to further modify the oligomer of Swaminathan by incorporating a linker at the amino-terminus to combine oligomer subunits as taught by Gildea. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success in order to improve solubility and reduce aggregation thereby facilitating the production of longer oligomers with similar makeup. Wherein Swaminathan teaches Swaminathan teaches oligomers containing 2 to 30 nucleomonomers are preferred but can be greater in length, oligomer subunits combining 12+12 (24 total) nucleomonomers of formula (I) separated by a linker are encompassed. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists (See MPEP 2144.05 (I)).
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Swaminathan (WO 93/24507, cited in previous action), Pokorski (J. Am. Chem. Soc., 2004, IDS filed October 13, 2022), and Fieldhouse (WO 2015/055994, cited in previous action) as applied to claims 1-3, 5-8, 10, 16-17, 25-26, and 29-30 as applied to claims 1-3, 5, 10, 16-17, and 25 above in view of Ueno (PLoS ONE, 2014, cited in previous action).
Regarding claim 24: As discussed above, Swaminathan, Pokorski, and Fieldhouse render obvious the oligomer with appropriate stereochemistry an amino terminus as recited by instant claims 1, 6, and 10. Swaminathan teaches the oligomers of the invention can be used as diagnostic reagents to detect the presence or absence of the target nucleic acid sequences to which they specifically bind (pg. 43, lines 23-26). The enhanced binding affinity of the invention oligomers is an advantage for their use as primers and probes (pg. 43, lines 26-28). Diagnostic tests cab be conducted by hybridization through either double or triple helix formation which is then detected by conventional means (pg. 43, lines 29-31).
Swaminathan does not teach wherein the oligomer has the specific sequence AGTCTGATAAGCTA as recited by instant claim 24.
However, Ueno teaches the use of DNA probes for diagnostic testing of microRNAs, which are biomarkers for cancer and other human diseases (abstract). Ueno specifically teaches the use of a capture probe comprising the sequence AGTCTGATAAGCTA for the detection of miR-21 (pg. 3, col. 1, para. 1).
Taken together it would have been prima facie obvious to a person of ordinary skill in the art to modify the oligomer of Swaminathan by using the base sequence AGTCTGATAAGCTA as taught by Ueno. A person of ordinary skill in the art would have the motivation to do so with a reasonable expectation of success as the art establishes this sequence can capture miR-21 for the purpose of diagnostic testing of microRNAs, and Swaminathan establishes that the oligomers can be effectively used for this purpose.
Response to Arguments
Applicant’s arguments and the declaration of Appella filed January 5, 2026 have been fully considered but they are not persuasive.
On pages 11 of Applicant’s response, Applicant argues that the Examiner argues that if the hydroxymethyl ethylene diamine group of compound 26
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was replaced with the appropriate ethylene diamine group, it would lead to the following structure (para. 1). Applicant argues that the synthetic method is in error as the reaction would not lead to the claimed compound, and is thus a non-enabling reference (para. 2). Applicant points to the declaration of Appella to support this point (para. 2). The declaration of Appella, filed January 5, 2026, argues that the position of the Examiner is that Swaminathan discloses the following reaction:
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(pg. 3, section 7). The declaration of Appella argues that such a transformation is not possible as the compound produced by such a reaction would have an extra CH2 group to the oxygen labeled 1.
However, the argument of the examiner is that Swaminathan (in combination with other references) renders obvious a method in which ethylene-diamine reagents are substituted for one another. In the cited case, the specific ethylene-diamine reagent in compound 26 is one that possesses a hydroxymethyl protected silicon group. Swaminathan teaches that synthesis of other monomers would follow a manner analogous to the synthetic scheme, by using alternative ethylene diamine reagents. The specific synthesis of compound 23 in Swaminathan is based upon the modification of L-serine into an ethylene diamine-type reagent, wherein the carboxylic acid group of L-serine is converted into the silicon protected compound 23 (See drawings, pg. 8, figure 5-1). Swaminathan teaches the following structure:
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(wherein X1 can be O), which does not have a silicon-protected hydroxymethyl group (drawings, figure 8). As stated above, and in the previous action.
“Swaminathan further teaches the synthetic scheme for preparing a monomer corresponding to formula (V) (pg. 33, lines 7-16). Swaminathan teaches synthesis of the monomer described above in figure 8, would be conducted in a manner analogous to the synthetic schemes shown in figures 5 and 6, with synthesis of compounds analogous to compound 26 starting from protected, substituted ethylene diamine having the ring constraints corresponding to those shown in Formula V (pg. 33, lines 10-16). “Figure 5 is directed towards the synthesis of a hydroxymethyl monomer:
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wherein the hydroxymethyl group is protected with a silicon group(pg. 19, lines 12-13, drawings pgs. 8-9, figures 5.1-5.2, drawings pg. 9, compound 26). Replacing the silicon protected hydroxymethyl ethylene diamine with the appropriate ethylene diamine group as suggested by Swaminathan would lead to the following monomer structure:
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wherein R1 is Fmoc (a nitrogen protecting group), R2 is H, and B is thymine (a nucleobase) (with appropriate stereochemistry as suggested by Pokorski, rendering obvious the compounds of claims 29-30).”.
Although compound 26 possesses a silicon protected hydroxymethyl group, this group is a part of the starting ethylene diamine reagent, and thus would not be present in the structure if replaced with the appropriate ethylene diamine reagent if one was following the synthesis of other compounds encompassed by Swaminathan. Swaminathan teaches the following structure:
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, which does not have a silicon-protected hydroxymethyl group (drawings, figure 8). Although the structure of 26 possesses this silicon-protected hydroxymethyl group, a person of ordinary skill attempting the make the figure 8 structure, would understand to utilize the appropriately protected ethylene diamine reagent. And wherein, as discussed above, X1 can be oxygen, a person of ordinary skill in the art would understand that the appropriate ethylene diamine reagent would naturally lead them to the following structure
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. It is not the argument of the examiner that the reactions explicitly described for compound 26 leads to the claimed compound, but substitution of the individual components during the synthesis naturally does. The argument of the Examiner is not that the reaction explicitly describes the production of the claimed compound using compound 23, it is that substitution of compound 23 does. In short, by modifying the following reaction scheme
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with the appropriate ethylene diamine (in view of figure 8) as suggested by Swaminathan, Swaminathan renders obvious the following reaction:
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wherein the silicon protected hydroxy methyl group is omitted. The Examiner notes that the reaction above was shown without appropriate stereochemistry, however, as discussed above in the 103 rejections, Pokorski is relied upon for such a teaching which is not contested in the current arguments.
Applicant’s reply is considered to be a bona fide attempt at a response and is being accepted as a complete response. The 35 USC § 103 rejections are maintained for reason of record and foregoing discussion.
Conclusion
No claims are allowed in this action.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMUEL L GALSTER whose telephone number is (571)270-0933. The examiner can normally be reached Monday - Friday 8:00 AM - 5:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Scarlett Y Goon can be reached at 571-270-5241. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/S.L.G./ Examiner, Art Unit 1693
/ANDREA OLSON/ Primary Examiner, Art Unit 1693