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 .
Election/Restrictions
Applicant’s election of group I, and SEQ ID NO 2 in the reply filed on 10/10/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 12, 14 and 16 require SEQ ID NO 3 which has a different sequence.
Claims 12, 14, 16, 18, 21, 23, 25-28, 30, 32 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species/invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/10/2025.
Claims 1, 3, 6-7, 9, 11, 17 are being examined.
Priority
The instant application was filed 05/04/2023 is a National Stage entry of PCT/US2021/058010 with an international filing date: 11/04/2021 and claims priority from Provisional Application 63110225 , filed 11/05/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/13/2023 and 10/10/2025 is being considered by the examiner.
Claim Objections
Claims 1, 3, 6-7, 9, 11, 17 are objected to because of the following informalities:
Claim 1 is objected to as it recites “Tra2β” but does not recite the full terminology for the acronym (or abbreviation). Claims are more concise when the first time an acronym (or abbreviation) is presented the full terminology is also presented. Finally an acronym (or abbreviation) may have alternative meanings to an artisan.
Claim 17 is objected to as it recites “Tra2β-PE” but does not recite the full terminology for the acronym (or abbreviation). Claims are more concise when the first time an acronym (or abbreviation) is presented the full terminology is also presented. Finally an acronym (or abbreviation) may have alternative meanings to an artisan.
Appropriate correction is required.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 3, 6-7, 17 is/are rejected under 35 U.S.C. 102(a)(1)/102(a)(2) as being anticipated by Bennnett (US20030232977).
With regards to claims 1, 3 , Bennett discloses an antisense oligonucleotide comprising a sequence that binds to a target sequence on an MRNA that encodes TRA2.beta (para [0006]; human splicing factor R/S-rich 10 (also known as SFRS10; TRA2-BETA; TRA2B; htra2-beta-1; htra2- beta1"; para (0017); "The present invention is directed to compounds, particularly antisense oligonucleotides, which are targeted to a nucleic acid encoding splicing factor R/S-rich 10, and which modulate the expression of splicing factor R/S-rich 10"), wherein the antisense oligonucleotide further comprises a 2'-O-methoxyethy! modification (para [0051]; "improving the pharmacokinetic properties of an oligonucleotide, or a group for improving the pharmacodynamic properties of an oligonucleotide, and other substituents having similar properties. A preferred modification includes 2'-methoxyethoxy (2'-O-CH2CH2OCH3, also known as 2'-O-(2-methoxyethyl) or 2'-MOE)"; para [0283}; "All compounds in Table 1 are chimeric oligonucleotides ("gapmers") 20 nucleotides in length, composed of a central “gap” region consisting of ten 2'-deoxynucleotides, which is flanked on both sides (5' and 3' directions) by five-nucleotide "wings". The wings are composed of 2'-methoxyethyl (2'-MOE) nucleotides. The internucleoside (backbone) linkages are phosphorothioate (P=S) throughout the oligonucleotide"). .
With regards to claim 4, Bennett teaches, “The internucleoside (backbone) linkages are phosphorothioate (P.dbd.S) throughout the oligonucleotide. “ (0283).
With regards to claim 5, Bennet claims, “wherein the modified internucleoside linkage is a phosphorothioate linkage.” (claim 4)
With regards to claim 7, Bennett teaches “Both controls are 2'-O-methoxyethyl gapmers (2'-O-methoxyethyls shown in bold) with a phosphorothioate backbone.” (0260)
MPEP 2111 states: Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. However, examples of claim language, although not exhaustive, that may raise a question as to the limiting effect of the language in a claim are:
(A) “adapted to” or “adapted for” clauses;
(B) “wherein” clauses; and
(C) “whereby” clauses.
The determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case. See, e.g., Griffin v. Bertina, 283 F.3d 1029, 1034, 62 USPQ2d 1431 (Fed. Cir. 2002) (finding that a “wherein” clause limited a process claim where the clause gave “meaning and purpose to the manipulative steps”). In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that when a “‘whereby’ clause states a condition that is material to patentability, it cannot be ignored in order to change the substance of the invention.” Id. However, the court noted (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” Id.
Claim 17 recites, “wherein binding of the antisense oligonucleotide to the pre-mRNA increases TRA23-PE inclusion.”
Thus the broadest reasonable interpretation is the oligonucleotide of claim 1 provides for this outcome.
Thus the teachings of claim 1 anticipate the claim.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1, 3, 6-7, 9, 11, 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bennett (US20030232977), Grellscheid (PLoS Genet 7(12): e1002390. doi:10.1371/journal.pgen.1002390) and hd86g01.x1 NCI_CGAP_GC6 Homo sapiens cDNA clone IMAGE:2916432 3' similar to TR:O15449 O15449 HTRA2-BETA-2, mRNA sequence (https://www.ncbi.nlm.nih.gov/nuccore/AW515680, Jan 7, 2011) .
With regards to claims 1, 3 , Bennett discloses an antisense oligonucleotide comprising a sequence that binds to a target sequence on an MRNA that encodes TRA2.beta (para [0006]; human splicing factor R/S-rich 10 (also known as SFRS10; TRA2-BETA; TRA2B; htra2-beta-1; htra2- beta1"; para (0017); "The present invention is directed to compounds, particularly antisense oligonucleotides, which are targeted to a nucleic acid encoding splicing factor R/S-rich 10, and which modulate the expression of splicing factor R/S-rich 10"), wherein the antisense oligonucleotide further comprises a 2'-O-methoxyethy! modification (para [0051]; "improving the pharmacokinetic properties of an oligonucleotide, or a group for improving the pharmacodynamic properties of an oligonucleotide, and other substituents having similar properties. A preferred modification includes 2'-methoxyethoxy (2'-O-CH2CH2OCH3, also known as 2'-O-(2-methoxyethyl) or 2'-MOE)"; para [0283}; "All compounds in Table 1 are chimeric oligonucleotides ("gapmers") 20 nucleotides in length, composed of a central “gap” region consisting of ten 2'-deoxynucleotides, which is flanked on both sides (5' and 3' directions) by five-nucleotide "wings". The wings are composed of 2'-methoxyethyl (2'-MOE) nucleotides. The internucleoside (backbone) linkages are phosphorothioate (P=S) throughout the oligonucleotide"). .
Bennett does not specifically teach SEQ ID NO 2.
However, Grellscheid teaches, “The Sfrs10 gene itself is alternatively spliced to five mRNA isoforms encoding at least 2 protein isoforms [20], [21], [22]. The major isoform encodes full length Tra2β protein. Full length Tra2β protein regulates its own levels through activating splicing inclusion of a poison exon (exon 2) into a second mRNA isoform.”
Further hd86g01.x1 NCI_CGAP_GC6 Homo sapiens cDNA clone IMAGE:2916432 3' similar to TR:O15449 O15449 HTRA2-BETA-2, mRNA sequence teaches nucleotides 408-442 which comprise SEQ ID NO 2.
Therefore it would have been prima facie obvious to one of skill in the art prior to the effective filing date of the claims to target the Tra2β poison exon comprising SEQ ID NO 2. The artisan would be motivated to target Tra2β with an antisense oligonucleotide to further characterize the how inhibition of Tra2β affects splicing and/or spermatogenesis. The artisan would have a reasonable expectation of success as the artisan is merely targeting known sequence identified in the art by 2’-MOE and phosphorothioate as they play a role in oligonucleotide stability.
With regards to claim 4, Bennett teaches, “The internucleoside (backbone) linkages are phosphorothioate (P.dbd.S) throughout the oligonucleotide. “ (0283).
With regards to claim 5, Bennet claims, “wherein the modified internucleoside linkage is a phosphorothioate linkage.” (claim 4)
With regards to claim 7, Bennett teaches “Both controls are 2'-O-methoxyethyl gapmers (2'-O-methoxyethyls shown in bold) with a phosphorothioate backbone.” (0260)
MPEP 2111 states: Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. However, examples of claim language, although not exhaustive, that may raise a question as to the limiting effect of the language in a claim are:
(A) “adapted to” or “adapted for” clauses;
(B) “wherein” clauses; and
(C) “whereby” clauses.
The determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case. See, e.g., Griffin v. Bertina, 283 F.3d 1029, 1034, 62 USPQ2d 1431 (Fed. Cir. 2002) (finding that a “wherein” clause limited a process claim where the clause gave “meaning and purpose to the manipulative steps”). In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that when a “‘whereby’ clause states a condition that is material to patentability, it cannot be ignored in order to change the substance of the invention.” Id. However, the court noted (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” Id.
Claim 17 recites, “wherein binding of the antisense oligonucleotide to the pre-mRNA increases TRA23-PE inclusion.”
Thus the broadest reasonable interpretation is the oligonucleotide of claim 1 provides for this outcome.
Thus the teachings of claim 1 anticipate the claim.
Summary
No claims are allowed.
The 2’-MOE appears to require the hand of man as searching revealed 2’-MOE is a second generation nucleotide modification.
Conclusion
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/Steven Pohnert/ Primary Examiner, Art Unit 1683