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 Status
Claims 4, 7-12 are amended.
Claims 12-16 are new.
Claims 1-16 are examined on the merits.
Priority
The applicant’s application is a U.S. National Stage application of PCT International Patent Application Serial No. PCT/KR2022/003884, filed 03/22/2022, which itself claims the benefit of Korean Patent Application Serial No. KR10-2021-0148357, filed 11/01/2021 is acknowledged.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Specification
The disclosure is objected to because of the following informalities: paragraphs [22] and [24] refer to underlined letters that are not visible in Table 1 of the specification.
Appropriate correction is required.
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 5-8, 15 and 16 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 recites the variables “nth” and “mth” without defining them, specifying their values or stablishing numerical ranges/limits for each variable.
Claim 6 depends from claim 5 and introduces positional limitations referencing the (n+1)th and (m+1)th. By depending of claim 5, claim 6 inherits the defect of undefined variables “n” and “m”.
Claim 7 recites oligonucleotides represented by SEQ ID NOs: 5-37 in Table 1. First, the claim does not require the sequence of the recited sequence identifiers, rather it requires the sequence identifiers to be used as a representation of the claimed oligonucleotides. It is unclear how much of the sequence of any recited sequence identifier is required by the claim given that it is only a stand in for the actual sequence. Furthermore, Table 1 only includes SEQ ID NOs: 1-30. As a result, SEQ ID NOs 31-37 lacks support and clear definition in Table 1, making it impossible to determine the sequence of those claimed species. Moreover, the claim recites, “wherein nucleotides indicated in bold and underlined letters in Table 1 below are modified nucleotides.” However, bold and underline cannot be seen in Table 1. Accordingly, the metes and bounds of claim 7 are unclear.
Claim 8 depends on claim 7 and is rejected for the same reasons applied to claim 7.
Claim 15 recites the variables “nth” and “mth” without defining them, specifying their values or stablishing numerical ranges/limits for each variable.
Claim 16 depends from claim 15 and introduces positional limitations referencing the (n+1)th and (m+1)th. By depending of claim 5, claim 6 inherits the defect of undefined variables “n” and “m”.
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.
Claims 1, 7, 9-10 and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Schlingensiepen et al. (“Schlingensiepen”, US 8,629,117 B2).
For the purpose of this rejection, claim 7 recites that the antisense oligonucleotide is “represented by” any one of SEQ ID NOs: 5-37. Under the broadest reasonable interpretation, the claim does not require exact identity across the entire length of the recited sequence identifier; rather, it uses the sequence identifiers merely as a stand-in representation for the claimed nucleotide sequence. Consequently, it is unclear how much of the sequence of any recited sequence identifier is required by the claim given that it serves only as a representation of the actual sequence.
Regarding claims 1 and 7, Schlingensiepen teaches medicament comprising a combination of at least one inhibitor of the effect of a substance negatively affecting an immune response, the substance selected from the group consisting of TGF-B. The inhibitor can be an oligonucleotide which may function as an antisense nucleotide (e.g., lines [37]-[51], column 1). Schlingensiepen teaches the antisense oligonucleotide of SEQ ID NO 71 that has 100% identity with SEQ ID NO: 1 and SEQ ID NO 5 of the instant claims (e.g., column 25, see alignment below).
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Schlingensiepen teaches oligonucleotides and/or nucleic acids have modifications wherein the modifications are 2'-O-derivatives, such as 2'-O-methyl or 2'-O-methoxyethoxy modifications of the sugar and/or modifications of the bases (e.g., lines [8]-[15], column 4).
Regarding claims 9-10, Schlingensiepen teaches oligonucleotides and/or nucleic acids have modifications wherein the modifications are phosphorothioate (S-ODN) internucleotide linkages and/or methylphosphonate internucleotide linkages and/or phosphoramidate linkages and/or peptide linkages (e.g., lines [8]-[15], column 4).
Regarding claim 11, Schlingensiepen teaches a method of treating hyperproliferative diseases, neoplasms or infectious diseases by administering a medicament of the invention to patients in need thereof. The method is especially useful for the treatment of leukemia, non-Hodgkin lymphoma, Hodgkin lymphoma, bronchial carcinoma, esophageal carcinoma, colorectal carcinoma, gastric carcinomas, intestinal tumors,
hepatic tumors, gall bladder and gallduct carcinomas, pancreatic carcinoma, anal carcinoma, breast cancer, ovarian carcinoma, cervical carcinoma, endometrium carcinoma, prostatic carcinoma, bladder carcinoma, malignant melanoma, brain tumors, and sarcomas (e.g., lines [23]-[35], column 4) (It reads on treatment of cancer). Schlingensiepen teaches the antisense oligonucleotide of SEQ ID NO 71 that has 100% identity with SEQ ID NO 1 of the instant claim. Schlingensiepen teaches oligonucleotides and/or nucleic acids have modifications wherein the modifications are 2'-O-derivatives, such as 2'-O-methyl (e.g., lines [8]-[15], column 4). Schlingensiepen teaches that the inhibitor of the effect of a substance negatively affecting an immune response is applied locally to a tumor or other pathologically affected site or organ and the stimulator positively effecting an immune response is applied systemically (e.g. i.v. or s.c. or orally) (e.g., line 43, column 4).
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 2-6, 8, 12-16 are rejected under 35 U.S.C. 103 as being unpatentable over Schlingensiepen et al. (“Schlingensiepen”, US 8,629,117 B2) as applied to claims 1, 7, 9-10 and 11 above, and further in view of Jaschinski et al. (“Jaschinski”, WO 2014/154843 A1, cited as reference 1, on IDS filed 05/21/2026).
The teachings of Schlingensiepen et al. are described above and applied as before.
Schlingensiepen does not teach one or more nucleotides at a 5'-end or one or more nucleotides at a 3'-end of the oligonucleotide are modified nucleotides. Schlingensiepen does not teach the first to nth nucleotides at the 5'-end of the oligonucleotide or the first to mth nucleotides at the 3'-end of the oligonucleotide are the modified nucleotides. Schlingensiepen does not teach the first to nth nucleotides at the 5'- end of the oligonucleotide and the first to mth nucleotides at the 3'-end of the oligonucleotide are the modified nucleotides. Schlingensiepen does not teach the oligonucleotide further comprises one or more modified nucleotides between the (n+1)th nucleotide at the 5'-end and the (m+1)th nucleotide at the 3'-end of the oligonucleotide. Schlingensiepen does not teach a modified nucleotide of an oligonucleotide represented by any one of SEQ ID NO: 5 is a 2'-0- methoxyethyl (MOE)-modified nucleotide. However, this is cured by Jaschinski.
Regarding claims 2-3, 12-13, Jaschinski teaches that the oligonucleotide or the pharmaceutical composition according to the invention is used in a method for the treatment of many different diseases, preferably benign or malignant tumors (e.g., line 28, page 10). Jaschinski teaches an oligonucleotide consisting of 10 to 18 nucleotides of selected regions of the TGF-β2 nucleic acid sequence, which comprises modified nucleotides such as LNA, ENA, polyalkylene oxide-, 2'-fluoro, 2'-O-methoxy and/or 2'-O-methyl modified nucleotides (e.g., abstract). Jaschinski teaches that the modifications are preferably located at the 5'- and/or 3'- end of the oligonucleotide. An oligonucleotide comprising such modified nucleotide is a modified oligonucleotide (e.g., line 18, page 4). Jaschinski teaches that the modified oligonucleotides show a significantly increased inhibition on TGF-β expression and activity, respectively, which results in an improved prevention and/or treatment of a malignant or benign tumor (e.g., line 29, page 7).
Regarding claims 4-6, 14-16, Jaschinski teaches modified nucleotides are for example arranged in a row, one directly next to the other, or in different patterns, where one or more unmodified nucleotides follow a modified nucleotide. For example, an oligonucleotide starts with one or more modified nucleotides followed by one or more, e.g., one, two, three or four, unmodified or unlocked nucleotides followed again by one or more modified nucleotides. In one embodiment both ends of the oligonucleotide comprise an identical pattern of modified and unmodified or unlocked nucleotides. Preferably the modified oligonucleotides comprise a series of 8 or 9 unlocked nucleotides (e.g., lines [21]-[31], page 4). Alternatively, a nucleotide at any other position in the oligonucleotide is modified, or at least one nucleotide at the 5'- and/or 3'-end of the oligonucleotide and at any other position in the oligonucleotide (e.g., line 1, page 5). Jaschinski teaches modified oligonucleotides, comprise at least one modified nucleotide, preferably LNA and/or ENA, at the 5'- and/or 3'-end of the oligonucleotide. In a preferred embodiment, the oligonucleotide comprises 1, 2, 3, or 4 LNAs or ENAs at the 5'-end, and 1, 2, 3, or 4 LNAs or ENAs at the 3'-end. In another preferred embodiment, the oligonucleotide comprises 1, 2, 3, or 4 LNAs or ENAs at the 5'-end or 3'-end, and a polyalkylene oxide such as TEG at the 3'- or 5'end (e.g., lines [23]-[29], page 7; Table 1, page 12) (It reads on incorporating one or more modified nucleotides in the internal region between the (n+1)th nucleotide at the 5’ end and the (m+1)th nucleotide at the 3’ end).
Regarding claim 8, Jaschinski teaches the 2’-O-methoxyethyl (MOE) modification (e.g., Fig. 2, page 3/6).
It would have been obvious to a person of ordinary skill in the art at the time of the invention to modify the antisense SEQ ID NO 71 taught by Schlingensiepen (that has 100% identity to SEQ ID NOs: 1 and 5 of instant claims) with the specific terminal and internal modification patterns taught by Jaschinski, because modifying the terminal 1-10 nucleotides and the internal positions of antisense oligonucleotides was a well-understood, routine technique in the art for stabilizing antisense oligonucleotides, a person of ordinary skill in the art would have had a reasonable expectation of success in applying the modification patterns taught by Jaschinski to the antisense SEQ ID NO 71 to obtain the modified antisense oligonucleotide and methods of claims 2-6, 8-10 and 12-16.
A person of ordinary skill in the art of designing antisense therapies against TGF-β in cancer as taught by Schlingensiepen would be motivated to look at stablished modification strategies in the antisense art, such as the modified oligonucleotides show a significantly increased inhibition on TGF-β expression and activity, which results in an improved treatment of a malignant or benign tumor as taught by Jaschinski.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JULIO GOMEZ RODRIGUEZ whose telephone number is (571)270-0991. The examiner can normally be reached Monday - Friday 8:00 am - 5:00 pm.
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/JULIO WASHINGTON GOMEZ RODRIGUEZ/Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637
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