0DETAILED ACTION
Election/Restrictions
Applicant's election with traverse of Group IV, claims 115-118 in the reply filed on November 3, 2025 is acknowledged and election of SEQ ID NO:1 in claim 115, antisense oligonucleotide (ASO) in claim 116, and SEQ ID NO: 10 in claim 118 in the reply filed on August 27, 2025 is acknowledged. The traversal is on the ground(s) that “[A]ccording to the Restriction Requirement, Groups IV and V lack unity of invention based on an alleged absence of a corresponding technical feature linking the claims. Notably, no reference is cited by the Restriction Requirement and is not clear how the Restriction Requirement arrived at the conclusion that no corresponding technical feature without doing so. Prior to Applicant’s disclosure, it was entirely unknown that certain of long noncoding RNA (IncRNA) or the knockdown thereof may sensitize glioma cells to cancer. Claim 115 recites ‘a therapeutically effective amount of an agent that knockdowns expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to any of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 and SEQ ID NO: 9 and a pharmaceutically acceptable carrier’ while claim 119 recites ‘administering to the subject a therapeutically effective amount of an agent that knockdowns expression of a IncRNA having at least about 70% sequence identity to any of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 and SEQ ID NO: 9.’ These features are corresponding technical features linking the claims. At least the claims of Group IV (115 through 118, 126, and 127) and Group V (119 through 125 and 128 through 131) should be examined together. Applicant also notes that independent claims 106 and 109 also recite these features and, thus, are linked such that they should be examined together. Finally, claim 110 targets radiation sensitizers and is, thus, related to the other groups and could be examined along with the others without undue burden”.
The above arguments have been fully considered and have not been found persuasive toward the withdrawal of the restriction requirement nor persuasive toward the relaxation of same such that Groups I to V will be examined together. Although applicant argues that “no reference is cited by the Restriction Requirement and is not clear how the Restriction Requirement arrived at the conclusion that no corresponding technical feature without doing so. Prior to Applicant’s disclosure, it was entirely unknown that certain of long noncoding RNA (IncRNA) or the knockdown thereof may sensitize glioma cells to cancer”, based on PCT Rules 13.1 and 13.2, there is no requirement that the office must make the restriction requirement by citing a prior art as argued by applicant. Since page 5 of the restriction requirement mailed on August 27, 2025 clearly stated that “[G]roups IV and V do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features. For example, a pharmaceutically acceptable carrier in claim 115 of Group IV is not required for Group V while treating brain cancer in a subject in need thereof in claim 119 of Group V is not required for Group IV”, the restriction requirement on Groups IV and V is proper. Furthermore, although applicant argues that “independent claims 106 and 109 also recite these features and, thus, are linked such that they should be examined together” and “claim 110 targets radiation sensitizers and is, thus, related to the other groups and could be examined along with the others without undue burden”, the restriction requirement is not based on undue burden as argument by applicant but is dependent on whether these claims lack the same or corresponding special technical features. In fact, page 4 of the restriction requirement mailed on August 27, 2025 clearly stated that “[G]roups I and II do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features. For example, a solid support in claim 106 of Group I is not required for Group II while step a) in claim 109 of Group II is not required for Group I. Groups I and III do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features. For example, a solid support in claim 106 of Group I is not required for Group III while step a) in claim 110 of Group III is not required for Group I”, and “[G]roups II and III do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features. For example, step a) in claim 109 of Group II is not required for Group III while step a) in claim 110 of Group III is not required for Group II”. Therefore, the requirement is still deemed proper and is made FINAL. Since applicant added new claims 126-131 in the amendment filed on August 27, 2025 wherein claims 126 and 127 are dependent on claim 115 and claims 128-131 are dependent on claim 119, claims 115-118, 126, and 127 and SEQ ID No: 1, 10, and 38 will be examined.
Drawings
The phrase “Figure 5B” overlaps with the phrase “SUBSTITUTE SHEET (RULE 26)” in Figure 5B, the phrase “Figure 5F” overlaps with the phrase “SUBSTITUTE SHEET (RULE 26)” in Figure 5F, a phrase comprising some words overlaps with the phrase “SUBSTITUTE SHEET (RULE 26)” in Figure 10B, the phrase “Figure 11B” overlaps with the phrase “SUBSTITUTE SHEET (RULE 26)” in Figure 11B, the phrase “Figure 12C” overlaps with the phrase “SUBSTITUTE SHEET (RULE 26)” in Figure 12C, and the phrase “Figure 12E” overlaps with the phrase “SUBSTITUTE SHEET (RULE 26)”. Applicant is required to remove these overlap phrases in Figures 5B, 5F, 10B, 11B, 12C, and 12E in response to this office action. No new matter may be introduced in the required drawing. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d).
Claim Objections
Claim 116 is objected to because of the following informality: “a miRNA, siRNA, antisense oligonucleotide (ASO), or morpholino” should be “a miRNA, a siRNA, an antisense oligonucleotide (ASO), or a morpholino”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Written Description
Claims 115-118, 126, and 127 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.
Applicant is referred to the interim guidelines on written description published on December 21, 1999 in the Federal Register at Volume 64, Number 244, pp.71427-71440.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111 (Fed. Cir. 1991), clearly states that “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. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” Vas-Cath Inc. v. Mahurkar, 19USPQ2d at 1117. The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed”. Vas-Cath Inc. v. Mahurkar, 19USPQ2d at 1116.
The specification provides adequate written description for a pharmaceutical composition comprising a therapeutically effective amount of an agent that knockdowns expression of a long noncoding RNA (IncRNA) consisting of SEQ ID NO: 1 wherein the agent that knockdowns expression of the IncRNA is an antisense oligonucleotide consisting of SEQ ID No:10 or 11
(see SEQ ID No:1 from Table 1 in page 16, SEQ ID Nos:10 and 11 from Table 2 in page 32, paragraphs [0212] to [0214], and Figures 7C and 8D to 8G of US 2023/0193250 A1, which is US publication of this instant case). However, the specification fails to adequately describe: (1) a pharmaceutical composition comprising a therapeutically effective amount of any kind of agent that knockdowns expression of a long noncoding RNA (IncRNA) having at least about
70% sequence identity to SEQ ID NO:1 and a pharmaceutically acceptable carrier as recited in claims 115, 117, and 127; (2) a pharmaceutical composition comprising a therapeutically effective amount of an agent that knockdowns expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 and a pharmaceutically acceptable carrier wherein the agent that knockdowns expression of the IncRNA is a miRNA, a siRNA, an antisense oligonucleotide (ASO), or a morpholino as recited in claims 116; (3) a pharmaceutical composition comprising a therapeutically effective amount of an agent that knockdowns expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 and a pharmaceutically acceptable carrier wherein the agent that knockdowns expression of the IncRNA is an ASO comprising a nucleic acid sequence having at least about
70% sequence identity to SEQ ID NO: 10 as recited in claim 118; and (4) a pharmaceutical composition comprising a therapeutically effective amount of an agent that knockdowns expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 and a pharmaceutically acceptable carrier wherein the agent that knockdowns expression of the IncRNA is an ASO comprising a nucleic acid sequence having at least about
70% sequence identity to SEQ ID NO: 38 as recited in claim 126. The claimed inventions as a whole are not adequately described if the claims require essential or critical elements which are not adequately described in the specification and which are not conventional in the art as of Applicants effective filing date. Possession may be shown by actual reduction to practice, clear depiction of the invention in a detailed drawing, or by describing the invention with sufficient relevant identifying characteristics (as it relates to the claimed inventions as a whole) such that a person skilled in the art would recognize that the inventor had possession of the claimed invention. Pfaff v. Wells Electronics, Inc., 48 USPQ2d 1641, 1646 (1998).
In this instant case, since, according to the specification, SEQ ID NO:1 is a long noncoding RNA (IncRNA), IncGRS-1 (CTC-338M12.4), SEQ ID Nos: 10 and 11 are antisense oligonucleotides targeting a long noncoding RNA (IncRNA), IncGRS-1 (CTC-338M12.4), and SEQ ID NO:38 is a full complementary sequence of SEQ ID NO:1 (see SEQ ID No:1 from Table 1 in page 16, SEQ ID Nos:10 and 11 from Table 2 in page 32, SEQ ID NO:38, paragraphs [0212] to [0214], and Figures 7C and 8D to 8G of US 2023/0193250 A1, which is US publication of this instant case), the pharmaceutical composition recited in claims 115, 117, and 127 is read as a pharmaceutical composition comprising a therapeutically effective amount of any kind of agent that knockdowns expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 and a pharmaceutically acceptable carrier, the pharmaceutical composition recited in claims 116 is read as a pharmaceutical composition comprising a therapeutically effective amount of an agent that knockdowns expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 and a pharmaceutically acceptable carrier wherein the agent that knockdowns expression of the IncRNA is a miRNA, a siRNA, an antisense oligonucleotide (ASO), or a morpholino, the pharmaceutical composition as recited in claims 118 is read as a pharmaceutical composition comprising a therapeutically effective amount of an agent that knockdowns expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 and a pharmaceutically acceptable carrier wherein the agent that knockdowns expression of the IncRNA is an ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO:10, and the pharmaceutical composition as recited in claim 126 is read as a pharmaceutical composition comprising a therapeutically effective amount of an agent that knockdowns expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO: 1 and a pharmaceutically acceptable carrier wherein the agent that knockdowns expression of the IncRNA is an ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO: 38. Therefore, claims 115-118, 126 and 127 encompass numerous unknown and unidentified IncRNAs and pharmaceutical compositions that miss from the disclosure and it is unclear whether these numerous unknown and unidentified pharmaceutical compositions still can knockdown expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO: 1. For example, since SEQ ID NO:1, which is a long noncoding RNA (IncRNA), contains 886 amino acids, about 70% identical to SEQ ID NO: 1 means that the differences between the nucleotides of the long noncoding RNA (IncRNA) recited in claims 115, 117, and 127 and the nucleotides of SEQ ID NO: 1 are about 266 nucleotides and the about 266 nucleotides can be located on any location of SEQ ID No: 1. Furthermore, since SEQ ID NO:10 only contain 16 nucleotides, about 70% identical to SEQ ID NO:10 means that the differences between the nucleotides of the ASO recited in claim 118 and the nucleotides of SEQ ID NO:10 are about 5 nucleotides and the about 5 nucleotides can be located on any location of SEQ ID No:10. Since SEQ ID NO:38, which is fully complementary to SEQ ID NO:1, contains 886 amino acids, about 70% identical to SEQ ID NO:38 means that the differences between the nucleotides of the ASO recited in claim 126 and the nucleotides of SEQ ID NO:38 are about 266 nucleotides and the about 266 nucleotides can be located on any location of SEQ ID No:38. Thus, these unknown and unidentified IncRNAs and pharmaceutical compositions recited in claims 115-118, 126, and 127 have not been described in the specification. In addition, since the specification and available arts do not show that these unknown and unidentified pharmaceutical compositions recited in claims 115-118, 126, and 127115-118, 126, and 127 can inhibit the expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO: 1, whether these numerous unknown and unidentified pharmaceutical compositions recited in claims 115-118, 126, and 127 can serve as agents that knockdown expression of the long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO: 1 is unpredictable. Therefore, the general knowledge and level of skill in the art do not supplement the omitted description because specific, not general, guidance is what is needed.
With limited disclosure provided by the specification, the skilled artisan cannot envision all unknown and unidentified IncRNAs and pharmaceutical compositions recited in claims 115-118, 126, and 127 and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method used. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of identifying it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir. 1991).
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481, 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Scope of Enablement
Claims 115-118, 126, and 127 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for knocking down expression of the long noncoding RNA (IncRNA) consisting of SEQ ID NO:1 using a pharmaceutical composition comprising a therapeutically effective amount of the ASO consisting of SEQ ID NO:10 and a pharmaceutical acceptable carrier when the pharmaceutical composition comprising a therapeutically effective amount of the ASO consisting of SEQ ID NO:10 and the pharmaceutical acceptable carrier enters cells comprising the long noncoding RNA (IncRNA) consisting of SEQ ID NO:1, does not reasonably provide enablement for: (1) knocking down expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 using a pharmaceutical composition comprising a therapeutically effective amount of any kind of agent and a pharmaceutical acceptable carrier as recited in claims 115, 117, and 127 when the pharmaceutical composition comprising a therapeutically effective amount of the any kind of agent and the pharmaceutical acceptable carrier enters cells comprising the long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO: 1; (2) knocking down expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 using a pharmaceutical composition comprising a therapeutically effective amount of any kind of miRNA, siRNA, antisense oligonucleotide (ASO) or morpholio and a pharmaceutical acceptable carrier as recited in claim 116 when the pharmaceutical composition comprising a therapeutically effective amount of the any kind of miRNA, siRNA, antisense oligonucleotide (ASO) or morpholio and the pharmaceutical acceptable carrier enters cells comprising the long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1; (3) knocking down expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 using a pharmaceutical composition comprising a therapeutically effective amount of an ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO:10 and a pharmaceutical acceptable carrier as recited in claim 118 when the pharmaceutical composition comprising a therapeutically effective amount of the ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO:10 and the pharmaceutical acceptable carrier enters cells comprising the long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1; and (4) knocking down expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 using a pharmaceutical composition comprising a therapeutically effective amount of an ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO:38 and a pharmaceutical acceptable carrier as recited in claim 126 when the pharmaceutical composition comprising a therapeutically effective amount of the ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO:38 and the pharmaceutical acceptable carrier enters cells comprising the long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988). Wands states at page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.”
The Nature of The Invention
The claims are drawn a pharmaceutical composition. The invention is a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
The Breadth of The Claims
Since, according to the specification, SEQ ID NO:1 is a long noncoding RNA (IncRNA), IncGRS-1 (CTC-338M12.4), SEQ ID Nos:10 and 11 are antisense oligonucleotides targeting a long noncoding RNA (IncRNA), IncGRS-1 (CTC-338M12.4), and SEQ ID NO:38 is a full complementary sequence of SEQ ID NO:1 (see SEQ ID No:1 from Table 1 in page 16, SEQ ID Nos:10 and 11 from Table 2 in page 32, SEQ ID NO:38, paragraphs [0212] to [0214], and Figures 7C and 8D to 8G of US 2023/0193250 A1, which is US publication of this instant case), claims 115, 117, and 127 are read as a pharmaceutical composition comprising a therapeutically effective amount of any kind of agent that knockdowns expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1, claims 116 is read as a pharmaceutical composition comprising a therapeutically effective amount of an agent that knockdowns expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 and a pharmaceutically acceptable carrier wherein the agent that knockdowns expression of the IncRNA is a miRNA, a siRNA, an antisense oligonucleotide (ASO), or a morpholino, claims 118 is read as a pharmaceutical composition comprising a therapeutically effective amount of an agent that knockdowns expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO: 1 and a pharmaceutically acceptable carrier wherein the agent that knockdowns expression of the IncRNA is an ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO:10, and claim 126 is read as a pharmaceutical composition comprising a therapeutically effective amount of an agent that knockdowns expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 and a pharmaceutically acceptable carrier wherein the agent that knockdowns expression of the IncRNA is an ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO: 38.
Working Examples
The specification provides one working examples (see pages 30-37 of US 2023/0193250 A1, which is US publication of this instant case). However, the specification provides no working example for (1) knocking down expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO: 1 using a pharmaceutical composition comprising a therapeutically effective amount of any kind of agent and a pharmaceutical acceptable carrier as recited in claims 115, 117, and 127 when the pharmaceutical composition comprising a therapeutically effective amount of the any kind of agent and the pharmaceutical acceptable carrier enters cells comprising the long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1; (2) knocking down expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO: 1 using a pharmaceutical composition comprising a therapeutically effective amount of any kind of miRNA, siRNA, antisense oligonucleotide (ASO) or morpholio and a pharmaceutical acceptable carrier as recited in claim 116 when the pharmaceutical composition comprising a therapeutically effective amount of any kind of miRNA, siRNA, antisense oligonucleotide (ASO) or morpholio and the pharmaceutical acceptable carrier enters cells comprising the long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO: 1; (3) knocking down expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 using a pharmaceutical composition comprising a therapeutically effective amount of an ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO:10 and a pharmaceutical acceptable carrier as recited in claim 118 when the pharmaceutical composition comprising a therapeutically effective amount of the ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO:10 and the pharmaceutical acceptable carrier enters cells comprising the long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1; and (4) knocking down expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 using a pharmaceutical composition comprising a therapeutically effective amount of an ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO:38 and a pharmaceutical acceptable carrier as recited in claim 126 when the pharmaceutical composition comprising a therapeutically effective amount of the ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO:38 and the pharmaceutical acceptable carrier enters cells comprising the long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO: 1.
The Amount of Direction or Guidance Provided and The State of The Prior Art
Although The specification provides one working examples (see pages 30-37 of US 2023/0193250 A1, which is US publication of this instant case), the specification provides no working example for (1) knocking down expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 using a pharmaceutical composition comprising a therapeutically effective amount of any kind of agent and a pharmaceutical acceptable carrier as recited in claims 115, 117, and 127 when the pharmaceutical composition comprising a therapeutically effective amount of the any kind of agent and the pharmaceutical acceptable carrier enters cells comprising the long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1; (2) knocking down expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 using a pharmaceutical composition comprising a therapeutically effective amount of any kind of miRNA, siRNA, antisense oligonucleotide (ASO) or morpholio and a pharmaceutical acceptable carrier as recited in claim 116 when the pharmaceutical composition comprising a therapeutically effective amount of any kind of miRNA, siRNA, antisense oligonucleotide (ASO) or morpholio
and the pharmaceutical acceptable carrier enters cells comprising the long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1; (3) knocking down expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO: 1 using a pharmaceutical composition comprising a therapeutically effective amount of an ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO:10 and a pharmaceutical acceptable carrier as recited in claim 118 when the pharmaceutical composition comprising a therapeutically effective amount of the ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO:10 and the pharmaceutical acceptable carrier enters cells comprising the long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1; and (4) knocking down expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 using a pharmaceutical composition comprising a therapeutically effective amount of an ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO:38 and a pharmaceutical acceptable carrier as recited in claim 126 when the pharmaceutical composition comprising a therapeutically effective amount of the ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO:38 and the pharmaceutical acceptable carrier enters cells comprising the long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1. Furthermore, there is no experimental condition and/or experimental data in the specification to support the claimed invention. During the process of the prior art search, the examiner has not found any prior art which is related to (1) knock down expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 using a pharmaceutical composition comprising a therapeutically effective amount of any kind of agent and a pharmaceutical acceptable carrier as recited in claims 115, 117, and 127 when the pharmaceutical composition comprising a therapeutically effective amount of the any kind of agent and the pharmaceutical acceptable carrier enters cells comprising the long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1; (2) knock down expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 using a pharmaceutical composition comprising a therapeutically effective amount of any kind of miRNA, siRNA, antisense oligonucleotide (ASO) or morpholio and a pharmaceutical acceptable carrier as recited in claim 116 when the pharmaceutical composition comprising a therapeutically effective amount of any kind of miRNA, siRNA, antisense oligonucleotide (ASO) or morpholio and the pharmaceutical acceptable carrier enters cells comprising the long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1; (3) knock down expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 using a pharmaceutical composition comprising a therapeutically effective amount of an ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO:10 and a pharmaceutical acceptable carrier as recited in claim 118 when the pharmaceutical composition comprising a therapeutically effective amount of the ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO:10 and the pharmaceutical acceptable carrier enters cells comprising the long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1; and (4) knock down expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 using a pharmaceutical composition comprising a therapeutically effective amount of an ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO:38 and a pharmaceutical acceptable carrier as recited in claim 126 when the pharmaceutical composition comprising a therapeutically effective amount of the ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO: 38 and the pharmaceutical acceptable carrier enters cells comprising the long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO: 1.
Level of Skill in The Art, The Unpredictability of The Art, and The Quantity of Experimentation Necessary
While the relative skill in the art is very high (the Ph.D. degree with laboratory experience), there is no predictability whether: (1) an expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 can be knocked down using a pharmaceutical composition comprising a therapeutically effective amount of any kind of agent and a pharmaceutical acceptable carrier as recited in claims 115, 117, and 127 when the pharmaceutical composition comprising a therapeutically effective amount of the any kind of agent and the pharmaceutical acceptable carrier enters cells comprising the long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1; (2) an expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 can be knocked down using a pharmaceutical composition comprising a therapeutically effective amount of any kind of miRNA, siRNA, antisense oligonucleotide (ASO) or morpholio and a pharmaceutical acceptable carrier as recited in claim 116 when the pharmaceutical composition comprising a therapeutically effective amount of the any kind of miRNA, siRNA, antisense oligonucleotide (ASO) or morpholio and the pharmaceutical acceptable carrier enters cells comprising the long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1; (3) an expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 can be knocked down using a pharmaceutical composition comprising a therapeutically effective amount of an ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO:10 and a pharmaceutical acceptable carrier as recited in claim 118 when the pharmaceutical composition comprising a therapeutically effective amount of the any kind of ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO:10 and the pharmaceutical acceptable carrier enters cells comprising the long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1; and (4) an expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 can be knocked down using a pharmaceutical composition comprising a therapeutically effective amount of an ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO:38 and a pharmaceutical acceptable carrier as recited in claim 126 when the pharmaceutical composition comprising a therapeutically effective amount of the ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO:38 and the pharmaceutical acceptable carrier enters cells comprising the long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1.
Although the specification teaches a pharmaceutical composition comprising a therapeutically effective amount of an agent that knockdowns expression of a long noncoding RNA (IncRNA) consisting of SEQ ID NO:1 wherein the agent that knockdowns expression of the IncRNA is an antisense oligonucleotide consisting of SEQ ID No: 10 or 11 (see SEQ ID No: 1 from Table 1 in page 16, SEQ ID Nos:10 and 11 from Table 2 in page 32, paragraphs [0212] to [0214], and Figures 7C and 8D to 8G of US 2023/0193250 A1, which is US publication of this instant case), the scopes of claims 115-118, 126, and 127 are much broader than the teachings of the specification because, as mentioned in above written description rejection, the pharmaceutical composition recited in claims 115, 117, and 127 is read as a pharmaceutical composition comprising a therapeutically effective amount of any kind of agent that knockdowns expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 and a pharmaceutically acceptable carrier, the pharmaceutical composition recited in claims 116 is read as a pharmaceutical composition comprising a therapeutically effective amount of an agent that knockdowns expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 and a pharmaceutically acceptable carrier wherein the agent that knockdowns expression of the IncRNA is a miRNA, a siRNA, an antisense oligonucleotide (ASO), or a morpholino, the pharmaceutical composition as recited in claims 118 is read as a pharmaceutical composition comprising a therapeutically effective amount of an agent that knockdowns expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 and a pharmaceutically acceptable carrier wherein the agent that knockdowns expression of the IncRNA is an ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO:10, and the pharmaceutical composition as recited in claim 126 is read as a pharmaceutical composition comprising a therapeutically effective amount of an agent that knockdowns expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 and a pharmaceutically acceptable carrier wherein the agent that knockdowns expression of the IncRNA is an ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO: 38. Therefore, claims 115-118, 126 and 127 encompass numerous unknown and unidentified IncRNAs and pharmaceutical compositions that miss from the disclosure and it is unclear whether these numerous unknown and unidentified pharmaceutical compositions still can knockdown expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1. For example, since SEQ ID NO:1, which is a long noncoding RNA (IncRNA), contains 886 amino acids, about 70% identical to SEQ ID NO: 1 means that the differences between the nucleotides of the long noncoding RNA (IncRNA) recited in claims 115, 117, and 127 and the nucleotides of SEQ ID NO:1 are about 266 nucleotides and the about 266 nucleotides can be located on any location of SEQ ID No:1. Furthermore, since SEQ ID NO:10 only contain 16 nucleotides, about 70% identical to SEQ ID NO: 10 means that the differences between the nucleotides of the ASO recited in claim 118 and the nucleotides of SEQ ID NO: 10 are about 5 nucleotides and the about 5 nucleotides can be located on any location of SEQ ID No: 10. Since SEQ ID NO:38, which is fully complementary to SEQ ID NO:1, contains 886 amino acids, about 70% identical to SEQ ID NO:38 means that the differences between the nucleotides of the ASO recited in claim 126 and the nucleotides of SEQ ID NO: 38 are about 266 nucleotides and the about 266 nucleotides can be located on any location of SEQ ID No: 38. Thus, these unknown and unidentified IncRNAs and pharmaceutical compositions recited in claims 115-118, 126, and 127 have not been described in the specification. In addition, since the specification and available arts do not show that these unknown and unidentified pharmaceutical compositions recited in claims 115-118, 126, and 127 can inhibit the expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1, whether these numerous unknown and unidentified pharmaceutical compositions recited in claims 115-118, 126, and 127 can serve as agents that knockdown expression of the long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO: 1 is unpredictable. Without knowing the information of these unknown and unidentified IncRNAs and pharmaceutical compositions in the specification, a skilled artisan does not know how to knock down expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO: 1 using the pharmaceutical compositions recited in claims 115-118, 126, and 127. Although the specification teaches that “[T]he term ‘microRNA’ or ‘miRNA’ as used herein refers to a small non-coding RNA molecule containing about 22 nucleotides that functions in RNA silencing and post-transcriptional regulation of gene expression. MicroRNAs function via base-pairing with complementary sequences within mRNA molecules. As a result, these mRNA molecules are silenced, by cleavage of the mRNA strand into two pieces, destabilization of the mRNA through shortening of its poly-A tail, and/or less efficient translation of the mRNA into proteins by ribosomes” and “the term ‘small interfering RNA’ or ‘siRNA,’ sometimes known as short interfering RNA or silencing RNA, refers to a class of double-stranded, noncoding RNA molecules of about 20-25 base pairs in length, similar to miRNA, which operate within the RNA interference (RNAi) pathway. They interfere with the expression of specific genes with complementary nucleotide sequences by degrading mRNA after transcription, thus preventing translation” (see paragraphs [0059] and [0060] of US 2023/0193250 A1, which is US publication of this instant case), since the specification does not show that an expression of a long noncoding RNA (lncRNA) having at least about 70% sequence identity to SEQ ID NO: 1 in cells comprising the long noncoding RNA (IncRNA) can be inhibited by a miRNA, a siRNA, or a morpholio, it is unpredictable how an expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO: 1 can be knocked down using a pharmaceutical composition comprising a therapeutically effective amount of any kind of miRNA, siRNA, antisense oligonucleotide (ASO) or morpholio as recited in claim 116.
Case law has established that “(t)o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation’.” In re Wright 990 F.2d 1557, 1561. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) it was determined that “[T]he scope of the claims must bear a reasonable correlation to the scope of enablement provided by the specification to persons of ordinary skill in the art”. The amount of guidance needed to enable the invention is related to the amount of knowledge in the art as well as the predictability in the art. Furthermore, the Court in Genentech Inc. v Novo Nordisk 42 USPQ2d 1001 held that “[I]t is the specification, not the knowledge of one skilled in the art that must supply the novel aspects of the invention in order to constitute adequate enablement”.
In view of above discussion, the skilled artisan will have no way to predict the experimental results. Accordingly, it is concluded that undue experimentation is required to make the invention as it is claimed. These undue experimentation at least includes to test whether: (1) an expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 can be knocked down using a pharmaceutical composition comprising a therapeutically effective amount of any kind of agent and a pharmaceutical acceptable carrier as recited in claims 115, 117, and 127 when the pharmaceutical composition comprising a therapeutically effective amount of the any kind of agent and the pharmaceutical acceptable carrier enters cells comprising the long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1; (2) an expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 can be knocked down using a pharmaceutical composition comprising a therapeutically effective amount of any kind of miRNA, siRNA, antisense oligonucleotide (ASO) or morpholio and a pharmaceutical acceptable carrier as recited in claim 116 when the pharmaceutical composition comprising a therapeutically effective amount of the any kind of miRNA, siRNA, antisense oligonucleotide (ASO) or morpholio and the pharmaceutical acceptable carrier enters cells comprising the long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1; (3) an expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 can be knocked down using a pharmaceutical composition comprising a therapeutically effective amount of an ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO:10 and a pharmaceutical acceptable carrier as recited in claim 118 when the pharmaceutical composition comprising a therapeutically effective amount of the any kind of ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO:10 and the pharmaceutical acceptable carrier enters cells comprising the long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1; and (4) an expression of a long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1 can be knocked down using a pharmaceutical composition comprising a therapeutically effective amount of an ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO:38 and a pharmaceutical acceptable carrier as recited in claim 126 when the pharmaceutical composition comprising a therapeutically effective amount of the ASO comprising a nucleic acid sequence having at least about 70% sequence identity to SEQ ID NO:38 and the pharmaceutical acceptable carrier enters cells comprising the long noncoding RNA (IncRNA) having at least about 70% sequence identity to SEQ ID NO:1.
Conclusion
In the instant case, as discussed above, the level of unpredictability in the art is high, the specification provides one with no guidance that leads one to claimed methods. One of skill in the art cannot readily anticipate the effect of a change within the subject matter to which the claimed invention pertains. Thus given the broad claims in an art whose nature is identified as unpredictable, the unpredictability of that art, the large quantity of research required to define these unpredictable variables, the lack of guidance provided in the specification, the absence of any working example related to claimed invention and the no teaching in the prior art balanced only against the high skill level in the art, it is the position of the examiner that it would require undue experimentation for one of skill in the art to perform the method of the claim as broadly written.
Conclusion
No claim is allowed.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Frank Lu, Ph.D., whose telephone number is (571)272-0746. The examiner can normally be reached on Monday-Friday from 9 A.M. to 5 P.M.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Dr. Anne Gussow, Ph.D., can be reached on (571)272-6047.
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/FRANK W LU/Primary Examiner, Art Unit 1683
January 30, 2026