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.
This office action is a response to applicant’s communication submitted May 7, 2024, wherein claim 7 was preliminarily amended.
Claims 1-11 are pending in this application.
Priority
This application is a 371 of PCT/JP2022/019139 filed April 27, 2022 and claims foreign priority to JP 2021-076609 filed April 28, 2021. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been received. The Examiner notes that no English translation was provided.
Specification
The disclosure is objected to because of the following informalities:
On page 33 of the instant specification (para. 0031), the phrase “the phosphorous atom to which they are attached to form a ring structure” should read “the phosphorus atom to which they are attached to form a ring structure” since the phrase is referring to an atom and not a composition.
Appropriate correction is required.
Claim Objections
Claims 1-6, 8, and 10 are objected to because of the following informalities:
In claim 1 the phrase “with a group removable under basic condition” should read “with a group removable under a basic condition”. This error repeats several times throughout the claim.
In claims 1, 8, and 10 the term “HDBU” should be defined the first time it appears.
In claim 1 the phrase “Q1 is a group removable under acidic condition” should read “Q1 is a group removable under an acidic condition”.
In claim 2 the phrase “The method according to claim 1 comprising further that the compound of the formula” should read “The method according to claim 1 further comprising that the compound of the formula”.
In claim 3 the phrase “The method according to claim 1 comprising further that the compound of the formula” should read “The method according to claim 1 further comprising that the compound of the formula”.
In claim 4 the phrase “The method according to claim 3 comprising further that the compound of the formula” should read “The method according to claim 3 further comprising that the compound of the formula”.
In claim 5 the phrase “The method according to claim 1 comprising further that the compound of the formula” should read “The method according to claim 1 further comprising that the compound of the formula”. See indefinite issues below.
In claim 6 the phrase “The method according to claim 1 comprising further that the compound of the formula” should read “The method according to claim 1 further comprising that the compound of the formula”. See indefinite issues below.
Appropriate correction is required.
Claim Rejections - 35 USC § 112 (a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-7 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims require “Phosphorus Reagent 1, Phosphorus Reagent 2 and onium reagent””. The claims do not require that the reagents possess any particular conserved structure, or other distinguishing feature. Thus, the claims are drawn to a genus of compounds that is defined by novelty.
To satisfy the written-description requirement, the specification must describe every element of the claimed invention in sufficient detail so that one of ordinary skill in the art would recognize that the inventor possessed the claimed invention at the time of filing. Vas-Cath, 935 F.3d at 1563; see also Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 [41 USPQ2d 1961] (Fed. Cir. 1997) (patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention”); In re Gosteli, 872 F.2d 1008, 1012 [10 USPQ2d 1614] (Fed. Cir. 1989) (“the description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed”). Thus, an applicant complies with the written-description requirement “by describing the invention, with all its claimed limitations, not that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F.3d at 1572.
According to the MPEP §2163 I. A. “the issue of a lack of adequate written description may arise even for an original claim when an aspect of the claimed invention has not been described with sufficient particularity such that one skilled in the art would recognize that the applicant had possession of the claimed invention. The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art.” The MPEP states in §2163 II 3 ii) “The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A), above), reduction to drawings (see i)(B), above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.”
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed. (See MPEP 2163 (3a)(II)). The instant specification recites embodiments that may be exemplary of phosphorus reagent 1 (pg. 32, para. 0030), phosphorus reagent 2 (pg. 33, para. 0031) and onium reagent (pg. 34, para. 0032), but the group itself is not clearly defined. The instant specification describes a large number of phosphorus containing reagents are encompassed by the genus which vary significantly in structure that is not particularly limiting (pg. 31-32, para. 0029). However, the instant specification only demonstrates two specific phosphorus containing species which are not representative of the entire genus claimed, especially considering the entire genus is not even limited to phosphorus containing species.
According to the MPEP §2163.02 Standard for Determining Compliance With the Written Description Requirement,
“The courts have described the essential question to be addressed in a description requirement issue in a variety of ways. An objective standard for determining compliance with the written description requirement is, “does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed". In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989). Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and that the invention, in that context, is whatever is now claimed. The test for sufficiency of support in a parent application is whether the disclosure of the application relied upon “reasonably conveys to the artisan that the inventor had possession at that time of the later claimed subject matter". Ralston Purina Co. v. Far-Mar-Co., Inc., 772 F.2d 1570, 1575, 227 USPQ 177, 179 (Fed. Cir. 1985) (quoting In re Kaslow, 707 F.2d 1366, 1375, 217 USPQ 1089, 1096 (Fed. Cir. 1983)).”
Applicants are reminded of what the U.S. Court of Appeals Federal Circuit wrote in University of California v. Eli Lilly and Co. 43 USPQ2d 1398, "In claims involving chemical materials, generic formulae usually indicate with specificity what the generic claims encompass. One skilled in the art can distinguish such a formula from others and can identify many of the species that the claims encompass. Accordingly, such a formula is normally an adequate description of the claimed genus." "A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is.” See Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen). "It is only a definition of a useful result rather than a definition of what achieves that result." "The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.")".
Therefore, the full breadth of the claim fails to meet the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision.
Claim Rejections - 35 USC § 112 (b)
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 1-7 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.
Regarding claims 1-7: The term “long-chain” in claim 1 is a relative term which renders the claim indefinite. The term “long-chain” 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. It is unclear as to what constitutes a long chain versus what would be considered a short chain. Claims 2-7 which depend from claim 1 are similarly rejected.
Regarding claims 1-7: Claims 1-2, 4 recite the phrases “Phosphorus Reagent 1, Phosphorus Reagent 2 and onium reagent”. However each of these phrases are not clearly defined within the instant specification. The instant specification recites embodiments that may be exemplary of phosphorus reagent 1 (pg. 32, para. 0030), phosphorus reagent 2 (pg. 33, para. 0031) and onium reagent (pg. 34, para. 0032), but the group itself is not clearly defined. Given the lack of a clear, explicit definition of these phrases, the scope of the compounds to be encompassed is unclear, rendering the claims indefinite. Claims 2-7 which depend from claim 1 are similarly rejected.
Regarding claims 2 and 6: Claims 2 and 6 recite the phrase “a scavenger”. The instant specification does not provide a clear explicit definition for the phrase. According to the instant specification a scavenger is a reagent for removing Q1, but as written in the claim it is not clear that this is the purpose (pg. 53, para. 0087). The lack of clarity and description of the phrase renders the claims indefinite.
Regarding claim 3: Claim 3 recites “is treated under a condition for removing the hydroxyl-protecting group”. There is a lack of antecedent basis for the phrase “the hydroxyl protecting group. It is also unclear what constitutes a hydroxyl-protecting group. Does being bound to a solid support and then cleaved constitute a protecting group? Thus, the lack of clarity renders claim 3 indefinite.
Regarding claim 4: Claim 4 recites “
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”. However, it is unclear from the claim that this formula is a limitation of a previously described formula (i.e. A-1). The formula could be interpreted as an entirely new formula that requires explicit definition of each individual. Thus, the scope of what is encompassed by the formula is unclear, thereby rendering the claim indefinite.
Regarding claim 5: Claim 5 recites:
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However, it is unclear from the claim that this formula is a limitation of a previously described formula (i.e. B-1). The formula could be interpreted as an entirely new formula that requires explicit definition of each individual. Thus, the scope of what is encompassed by the formula is unclear, thereby rendering the claim indefinite.
Regarding claim 5: Claim depends from claim 1 and recites:
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. However, this formula is defined in claim 3, not in claim 1. Thus, the scope of what is encompassed by the formula is unclear, thereby rendering the claim indefinite.
Regarding claim 6: Claim 6 recites: a compound of the formula [A-0]:
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However, it is unclear from the claim that this formula is a limitation of a previously described formula (i.e. A-1). The formula could be interpreted as an entirely new formula that requires explicit definition of each individual. Thus, the scope of what is encompassed by the formula is unclear, thereby rendering the claim indefinite.
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 9 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 9: Claim 9 recites specific compounds of formula [B-1] according to claim 8, however, several compounds recited do not specify the L’ group as either
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(salt) as required by instant claim 8. For example,
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.The claim is thus interpreted wherein these specific compounds the L’ group is OH (not a salt), which is not encompassed by the formula as recited by instant claim 8. Thus claim 9 expands, rather than limits instant claim 8.
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.
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 1-2, and 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Kotobuki (CA 3099778, IDS filed March 28, 2025) in view of over Bhadra (Tetrahedron Letters, 2015, IDS filed March 28, 2025) and Powles (Org. Biomol. Chem., 2012, cited on PTO-892). The supplementary material for Bhadra was also provided in the IDS filed March, 28, 2025.
Regarding claims 1-2 and 6-7: Kotobuki teaches the following synthesis
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(pg. 31, top of page) Kotobuki teaches the compound C-1 can be treated with an acid to remove the Q1 group and generate compound E-1
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(pg. 36, para. 0066-0067). Kotobuki teaches the specific examples of A-1:
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(pgs. 83-84, table 3). Kotobuki teaches the specific examples of B-1
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(pgs. 20-21, para. 0034, table 1). This compounds react as shown above to form corresponding compounds of C-1. Kotobuki teaches the n values can range from 1 to 25 for A-1 (pg. 13, top half of page). Kotobuki teaches the p values can range from 1 to 5 for B-1 (pg. 19, chem. 22, bottom half of page). Kotobuki teaches “The "optionally protected nucleic acid base" refers to an unprotected "nucleic acid base" and/or a protected nucleic acid base, and examples thereof include adenine, guanine, hypoxanthine, cytosine, thymine, uracil, adenine (Anz) having an amino group protected by benzoyl, cytosine (CBz) having an amino group protected by benzoyl, and guanine (GCE,Pac) having a hydroxyl group protected by 2-cyanoethyl and an amino group protected by phenoxyacetyl.” (pg. 26, middle of page).
The method of Kotobuki differ from the instantly claimed method utilizes a chlorophosphoramidate instead of an H-phosphonate triethylammonium salt. To clarify, Kotobuki teaches this group:
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, while the instantly claimed compounds in the method possess this group:
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. The method does not teach following condensation A-1 and B-1 are treated with an oxidizing agent and an organic amine to obtain C-1.
However, Bhadra teaches the synthesis of T-containing phosphorodiamidate morpholino oligomers by H-phosphate methods on solid support (abstract). Bhadra teaches the following synthesis of an H-phosphonate T monomer:
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(pg. 4566, col. 1, scheme 2). Bhadra teaches this monomer is utilized in the solid phase synthesis of PMO via H-phosphonate chemistry (pg. 4566, col. 2, para. 1, scheme 3). Bhadra teaches 5’-chlorophosphoramidate morpholino monomers are unstable in solution (pg. 4565, col. 1, para. 2). Bhadra teaches the H-phosphonate method with a T morpholino monomer is unique in comparison to chlorophosphoramidate method as it can be transferred to a DNA synthesizer and is stable in solution (pgs. 4567-4568, bridging para.).
Taken together it would have been prima facie obvious to a person of ordinary skill in the art to modify the compound of Kotobuki such that the chlorophosphoramidate (
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) is replaced with an H-phosphonate triethylammonium salt(
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) as taught by Bhadra which is subsequently oxidized in the presence of an oxidizing agent and an organic amine. A person of ordinary skill in the art would have had the motivation to do with a reasonable expectation of success as the H-phosphonate triethylammonium salts are known in the art for the synthesis of PMO oligomers which are subsequently oxidized and reacted with an organic amine to form a PMO and H-phosphonate triethylammonium salts are stable in solution compared to chlorophosphoramidate reagents. Bhadra teaches that following activation and coupling steps the oligomer is subsequently subjected to an oxidizing agent (iodine) and an organic amine (Me2NH)
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(Supporting information, pg. 4, scheme).
The method further differs in the Kotobuki and Bhadra do not teach wherein the condensation between A-1 and B-2 is in performed in the presence of phosphorus reagent 1, phosphorus reagent 2, or an onium reagent in the presence of a base prior to oxidation. According to the instant specification diphenyl chlorophosphite is an example of these reagents (pgs. 31-32, para. 0029).
However, Bhadra establishes that H-phosphonate triethylammonium salts are viable compounds in both PMO (
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) and DNA syntheses (
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) of oligomers (pg. 4566, col. 1, scheme 2, pg. 4567, scheme 4). Additionally Powles teaches that coupling reactions for the synthesis of most oligonucleotides utilize phosphate esters, phosphoramidites, or H-phosphonates (pg. 5940, col. 2, para. 1). Powles teaches that H-phosphonates are a simple and efficient way to produce dinucleoside, which can be activated with diphenylchlorophosphate and pyridine (i.e. a base) (pg. 5940, col. 2, para. 1, scheme 1).
Taken together it would have been prima facie obvious to modify the method such that A-1 and B-1 are reacted in the presence of an activator and base, such as diphenylchlorophosphate and pyridine as taught by Powles. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as activator systems, such as those taught by Powles, are a known technique in the art for forming oligonucleotides with H-phosphonate chemistry.
Claims 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Kotobuki (CA 3099778, IDS filed March 28, 2025) in view of over Bhadra (Tetrahedron Letters, 2015, IDS filed March 28, 2025). The supplementary material for Bhadra was also provided in the IDS filed March, 28, 2025.
Regarding claims 8-9: Kotobuki teaches the preparation of PMO using the following synthesis
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(pg. 31, top of page). Kotobuki teaches the specific examples of A-1:
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(pgs. 83-84, table 3). Kotobuki teaches the specific examples of B-1
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(pgs. 20-21, para. 0034, table 1). This compounds react as shown above to form corresponding compounds of C-1 via the chlorophosphoramidate method. Kotobuki teaches that the p value in [B-1] is suitably an integer from 1 to 10 (pg. 19, chem. 22). Kotobuki teaches the amino group or hydroxyl group of the nucleic acid base for BP may be protected (pg. 26, top paragraph).
The compounds of Kotobuki differ from the instantly claimed compounds in that a chlorophosphoramidate is present instead of an H-phosphonate triethylammonium salt. To clarify, Kotobuki teaches this group:
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, while the instantly claimed compounds possess this group:
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.
However, Bhadra teaches the synthesis of T-containing phosphorodiamidate morpholino oligomers by H-phosphate methods on solid support (abstract). Bhadra teaches the following synthesis of an H-phosphonate T monomer:
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(pg. 4566, col. 1, scheme 2). Bhadra teaches this monomer is utilized in the solid phase synthesis of PMO via H-phosphonate chemistry (pg. 4566, col. 2, para. 1, scheme 3). Bhadra teaches 5’-chlorophosphoramidate morpholino monomers are unstable in solution (pg. 4565, col. 1, para. 2). Bhadra teaches the H-phosphonate method with a T morpholino monomer is unique in comparison to chlorophosphoramidate method as it can be transferred to a DNA synthesizer and is stable in solution (pgs. 4567-4568, bridging para.).
Taken together it would have been prima facie obvious to a person of ordinary skill in the art to modify the compound of Kotobuki such that the chlorophosphoramidate (
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) is replaced with an H-phosphonate triethylammonium salt(
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) as taught by Bhadra. A person of ordinary skill in the art would have had the motivation to do with a reasonable expectation of success as the H-phosphonate triethylammonium salts are known in the art for the synthesis of PMO oligomers and are stable in solution compared to chlorophosphoramidate. Kotobuki teaches “The "optionally protected nucleic acid base" refers to an unprotected "nucleic acid base" and/or a protected nucleic acid base, and examples thereof include adenine, guanine, hypoxanthine, cytosine, thymine, uracil, adenine (Anz) having an amino group protected by benzoyl, cytosine (CBz) having an amino group protected by benzoyl, and guanine (GCE,Pac) having a hydroxyl group protected by 2-cyanoethyl and an amino group protected by phenoxyacetyl.” (pg. 26, middle of page). Kotobuki demonstrates the particular protected B-1 compound with the following structure:
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(pgs. 19-20, table 1, morG). Given that Kotobuki teaches a large amount of known protected bases and the H-phosphonate TEA reagent is encompassed by the prior art, so too are the specific compounds recited by claim 9.
Claims 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over Kotobuki (CA 3099778, IDS filed March 28, 2025) and Bhadra (Tetrahedron Letters, 2015, IDS filed March 28, 2025) as applied to claims 8-9 above in view of Link (Link Technologies, Guidebook for the synthesis of Oligonucleotides, 2015, cited on PTO-892) and Sinha (US 2021/0130379, cited on PTO-892, filed October 30, 2020). The supplementary material for Bhadra was also provided in the IDS filed March, 28, 2025.
Regarding claims 10-11: As discussed above the prior art render obvious the compounds of claims 8-9. Bhadra establishes that H-phosphonate triethylammonium salts are viable compounds in both PMO (
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) and DNA syntheses (
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) of oligomers (pg. 4566, col. 1, scheme 2, pg. 4567, scheme 4).
They do not teach wherein the compound is an H-phosphonate DBU salt.
However, Link teaches known reagents for solid-phase oligonucleotide assembly by using H-phosphonates (pg. 61, para. 2). Link teaches the following reagents which differ in their salt form:
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(pg. 60, bottom of page, compounds 2005 and 2035). Additionally Sinha contemplates morpholino H-phosphonate monomer DBU salts to be used in the synthesis of PMOs
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(abstract, pg. 6, bottom right of page).
Taken together, it would have been prima facie obvious to modify the compound such that a DBU salt is utilized instead of a TEA salt as taught by Link and Sinha. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as both these salts are known in the art for H-phosphonate chemistry and the art establishes H-phosphonate chemistry is compatible with PMO and DNA synthesis. Wherein the salts are established equivalents, it is prima facie obvious to substitute equivalents known for the same purpose (See MPEP 2144.03 (II)). As discussed above, Kotobuki teaches the amino group or hydroxyl group of the nucleic acid base for BP may be protected (pg. 26, top paragraph). Kotobuki teaches “The "optionally protected nucleic acid base" refers to an unprotected "nucleic acid base" and/or a protected nucleic acid base, and examples thereof include adenine, guanine, hypoxanthine, cytosine, thymine, uracil, adenine (Anz) having an amino group protected by benzoyl, cytosine (CBz) having an amino group protected by benzoyl, and guanine (GCE,Pac) having a hydroxyl group protected by 2-cyanoethyl and an amino group protected by phenoxyacetyl.” (pg. 26, middle of page). Kotobuki demonstrates the particular protected B-1 compound with the following structure:
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(pgs. 19-20, table 1, morG). Given that Kotobuki teaches a large amount of known protected bases and the H-phosphonate DBU reagent is encompassed by the prior art, so too are the specific compounds recited by claim 11.
Conclusion
No claims are allowed in this action.
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/S.L.G./Examiner, Art Unit 1693
/ANDREA OLSON/Primary Examiner, Art Unit 1693