DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This Office action is in response to the communication filed 3-9-23.
Claims 12-27 are pending in the instant application.
Claim Objections
Claims 15, 21 and 23 are objected to because of the following informalities: The claims list sequences with accompanying SEQ ID Nos.
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.
Claims 26 and 27 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for the in vitro inhibition of EGFR expression in vitro comprising the transfection of SEQ ID No. 1 or 2, does not reasonably enable methods of preventing and/or treating any EGFR related disease in any subject.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The following factors have been considered in determining that the specification does not enable the skilled artisan to make and/or use the invention over the broad scope claimed.
The breadth of the claims:
The claims are drawn to methods of preventing and/or treating any EGFR related disease comprising the administration of an interfering RNA comprising SEQ ID No. 1 and//or SEQ ID No. 2.
Teachings in the art and in the specification.
Teachings in the art:
Roberts et al (Nature Rev., Drug Discovery, Vol. 19, pages 673-694 (2020)) teaches on page 673 that “achieving efficient oligonucleotide delivery, particularly to extrahepatic tissues, remains a major translational limitation.”
Kobelt et al (Cancer Gene Therapy in Gene Therapy of Cancer: Methods and Protocols, Methods in Molecular Biology, Vol. 2521, pages 1-15 (Springer Nature 2022)) teach that limitations to cancer gene therapy relate to limitations in gene transfer efficiency (see esp. pages 3-4).
In addition, Osborn et al (Nucleic Acid Therapeutics, Vol. 28, No. 3, pages 128-136 (2018)) state the following about challenges to siRNA delivery on page 128:
…The primary challenge facing the clinical development of small interfering RNAs (siRNA) has been overcoming barriers that impede in vivo delivery. siRNAs are large, polyanionic macromolecules with intrinsically poor pharmacological properties. Unmodified siRNAs have a half-life of less than 5 min in circulation, and they do not permeate intact cellular membranes…
Damase et al (Frontiers in Bioengineering and Biotechnology, Vol. 9, Article 628137, pages 1-24 (2021)) on page 13 also address the challenges of using RNA-based drugs:
Targeted delivery is a major hurdle for effective RNA therapeutics, a hurdle that must be overcome to broaden the application of clinical translation of this type of therapeutic. …There is a need for novel delivery vehicles that will deliver the RNA drug to the site of therapeutic action facilitating the entry of the RNA drug into the cytoplasm where it may exert its effect…
Bost et al (ACS Nano, Vol. 15, pages 13993-14021 (2021)) on page 13993 also address the current challenges of oligonucleotide therapeutics:
…Historically, the largest hindrance to the widespread usage of ON therapeutics has been their inability to effectively internalize into cells and escape from endosomes to reach their molecular targets in the cytosol or nucleus…
Teachings in the specification:
The specification teaches the transfection in vitro of 293T cells of SEQ ID No. 1 or 2, each sequence additionally comprising dTdT overhangs on the 3’ termini. The examples provided in the instant specification, of the in vitro inhibition, are not representative or correlative of the broad claims encompassing the ability to prevent or treat any EGFR related disease in any subject, as instantly claimed.
In light of the teachings in the art and the specification, one skilled in the art would not accept on its face the examples provided in the instant disclosure as being correlative or representative of the ability to provide treatment effects in a subject. Since the specification fails to provide the requisite guidance for the treatment in any subject, and since determination of the factors required for accomplishing this in any subject is highly unpredictable, it would require undue experimentation to practice the invention over the broad scope claimed.
For these reasons, the instant rejection for lacking enablement over the full scope claimed is proper.
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) 12-27 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Avidity Biosciences, Inc. (USPN 12,234,290).
Avidity Biosciences Inc. (USPN 12,234,290) teach compositions and methods of treatment of an EGFR related disease comprising the administration of pharmaceutical compositions comprising siRNA of SEQ ID No. 1 and/or SEQ ID No. 2, which siRNA optionally comprise overhangs on the 3’ termini, which compositions also optionally comprise vector delivery systems (see entire document, esp. ¶¶ 240, 757-758, 767-768, 966, 985, see also the alignments set forth below between instantly claimed SEQ ID Nos. 1 and 2, and SEQ ID Nos. 1558, 1485, 1487 and 1488).
Alignments with SEQ ID Nos. 1 and 2:
RESULT 3
US-19-031-247-1558
(NOTE: this sequence has 2 duplicates in the database searched.
See complete list at the end of this report)
Sequence 1558, US/19031247 USPN 12,234,290
GENERAL INFORMATION
APPLICANT: AVIDITY BIOSCIENCES, INC. (en)
TITLE OF INVENTION: NUCLEIC ACID-POLYPEPTIDE COMPOSITIONS AND USES THEREOF (en)
FILE REFERENCE: 45532-707.309
CURRENT APPLICATION NUMBER: US/19/031,247
CURRENT FILING DATE: 2025-01-17
NUMBER OF SEQ ID NOS: 2117
SEQ ID NO 1558
LENGTH: 21
TYPE: DNA
FEATURE:
NAME/KEY: misc_feature
LOCATION: 1..21
QUALIFIERS: note = Description of Artificial Sequence: Synthetic
oligonucleotide
FEATURE:
NAME/KEY: source
LOCATION: 1..21
QUALIFIERS: mol_type = other DNA
organism = synthetic construct
FEATURE:
NAME/KEY: modified_base
LOCATION: 1
QUALIFIERS: mod_base = OTHER
note = 2'-O-Methyl nucleotide
FEATURE:
NAME/KEY: modified_base
LOCATION: 2
QUALIFIERS: mod_base = OTHER
note = 2'-O-Methyl nucleotide
FEATURE:
NAME/KEY: modified_base
LOCATION: 3
QUALIFIERS: mod_base = OTHER
note = 2'-fluoro nucleotide
FEATURE:
NAME/KEY: modified_base
LOCATION: 4
QUALIFIERS: mod_base = OTHER
note = 2'-O-Methyl nucleotide
FEATURE:
NAME/KEY: modified_base
LOCATION: 5
QUALIFIERS: mod_base = OTHER
note = 2'-fluoro nucleotide
FEATURE:
NAME/KEY: modified_base
LOCATION: 6
QUALIFIERS: mod_base = OTHER
note = 2'-O-Methyl nucleotide
FEATURE:
NAME/KEY: modified_base
LOCATION: 7
QUALIFIERS: mod_base = OTHER
note = 2'-fluoro nucleotide
FEATURE:
NAME/KEY: modified_base
LOCATION: 8
QUALIFIERS: mod_base = OTHER
note = 2'-O-Methyl nucleotide
FEATURE:
NAME/KEY: modified_base
LOCATION: 9
QUALIFIERS: mod_base = OTHER
note = 2'-fluoro nucleotide
FEATURE:
NAME/KEY: modified_base
LOCATION: 10
QUALIFIERS: mod_base = OTHER
note = 2'-O-Methyl nucleotide
FEATURE:
NAME/KEY: modified_base
LOCATION: 11
QUALIFIERS: mod_base = OTHER
note = 2'-fluoro nucleotide
FEATURE:
NAME/KEY: modified_base
LOCATION: 12
QUALIFIERS: mod_base = OTHER
note = 2'-O-Methyl nucleotide
FEATURE:
NAME/KEY: modified_base
LOCATION: 13
QUALIFIERS: mod_base = OTHER
note = 2'-fluoro nucleotide
FEATURE:
NAME/KEY: modified_base
LOCATION: 14
QUALIFIERS: mod_base = OTHER
note = 2'-O-Methyl nucleotide
FEATURE:
NAME/KEY: modified_base
LOCATION: 15
QUALIFIERS: mod_base = OTHER
note = 2'-fluoro nucleotide
FEATURE:
NAME/KEY: modified_base
LOCATION: 16
QUALIFIERS: mod_base = OTHER
note = 2'-O-Methyl nucleotide
FEATURE:
NAME/KEY: modified_base
LOCATION: 17
QUALIFIERS: mod_base = OTHER
note = 2'-fluoro nucleotide
FEATURE:
NAME/KEY: modified_base
LOCATION: 18
QUALIFIERS: mod_base = OTHER
note = 2'-O-Methyl nucleotide
FEATURE:
NAME/KEY: modified_base
LOCATION: 19
QUALIFIERS: mod_base = OTHER
note = 2'-fluoro nucleotide
FEATURE:
NAME/KEY: modified_base
LOCATION: 20
QUALIFIERS: mod_base = OTHER
note = deoxy-thymine phosphorothioate
FEATURE:
NAME/KEY: misc_feature
LOCATION: 1..19
QUALIFIERS: note = RNA
RESULT 4
PCT-US17-25431-1488
(NOTE: this sequence has 12 duplicates in the database searched.
See complete list at the end of this report)
Sequence 1488, PC/TUS1725431
GENERAL INFORMATION
APPLICANT: AVIDITY BIOSCIENCES LLC
TITLE OF INVENTION: EGFR NUCLEIC ACIDS AND USES THEREOF
FILE REFERENCE: 45532-709.601
CURRENT APPLICATION NUMBER: PCT/US17,25431
CURRENT FILING DATE: 2017-03-31
PRIOR APPLICATION NUMBER: 62/317,105
PRIOR FILING DATE: 2016-04-01
NUMBER OF SEQ ID NOS: 1893
SEQ ID NO 1488
LENGTH: 21
TYPE: DNA
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Description of Artificial Sequence: Synthetic
oligonucleotide
FEATURE:
OTHER INFORMATION: Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide
Query Match 100.0%; Score 19; Length 21;
Best Local Similarity 100.0%;
Matches 19; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AAGUCCAUCGACAUGUUGC 19
|||||||||||||||||||
Db 1 AAGUCCAUCGACAUGUUGC 19
RESULT 5
PCT-US17-25431-1485/c
(NOTE: this sequence has 12 duplicates in the database searched.
See complete list at the end of this report)
Sequence 1485, PC/TUS1725431
GENERAL INFORMATION
APPLICANT: AVIDITY BIOSCIENCES LLC
TITLE OF INVENTION: EGFR NUCLEIC ACIDS AND USES THEREOF
FILE REFERENCE: 45532-709.601
CURRENT APPLICATION NUMBER: PCT/US17,25431
CURRENT FILING DATE: 2017-03-31
PRIOR APPLICATION NUMBER: 62/317,105
PRIOR FILING DATE: 2016-04-01
NUMBER OF SEQ ID NOS: 1893
SEQ ID NO 1485
LENGTH: 21
TYPE: DNA
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Description of Artificial Sequence: Synthetic
oligonucleotide
FEATURE:
OTHER INFORMATION: Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide
Query Match 100.0%; Score 19; Length 21;
Best Local Similarity 73.7%;
Matches 14; Conservative 5; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AAGUCCAUCGACAUGUUGC 19
|||:|||:|||||:|::||
Db 20 AAGTCCATCGACATGTTGC 2
RESULT 6
PCT-US17-25431-1487/c
(NOTE: this sequence has 12 duplicates in the database searched.
See complete list at the end of this report)
Sequence 1487, PC/TUS1725431
GENERAL INFORMATION
APPLICANT: AVIDITY BIOSCIENCES LLC
TITLE OF INVENTION: EGFR NUCLEIC ACIDS AND USES THEREOF
FILE REFERENCE: 45532-709.601
CURRENT APPLICATION NUMBER: PCT/US17,25431
CURRENT FILING DATE: 2017-03-31
PRIOR APPLICATION NUMBER: 62/317,105
PRIOR FILING DATE: 2016-04-01
NUMBER OF SEQ ID NOS: 1893
SEQ ID NO 1487
LENGTH: 21
TYPE: DNA
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Description of Artificial Sequence: Synthetic
oligonucleotide
FEATURE:
OTHER INFORMATION: Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide
Query Match 100.0%; Score 19; Length 21;
Best Local Similarity 73.7%;
Matches 14; Conservative 5; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AAGUCCAUCGACAUGUUGC 19
|||:|||:|||||:|::||
Db 19 AAGTCCATCGACATGTTGC 1
Claim(s) 12-25 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Dharmacon, Inc. (US 2005/0255487).
Dharmacon, Inc. (US 2005/0255487) teach pharmaceutical compositions comprising siRNA of SEQ ID No. 1 and/or SEQ ID No. 2, which siRNA optionally comprise overhangs on the 3’ termini, which compositions also optionally comprise vector delivery systems (see entire document, esp. ¶¶ 0007, 0117, 0434, 0464, 0482. See alignments between instantly claimed SEQ ID Nos. 1 and 2, and SEQ ID Nos. 2509906,
Alignments with SEQ ID Nos. 1 and 2:
RESULT 2
US-10-940-892-2509906/c
(NOTE: this sequence has 8 duplicates in the database searched.
See complete list at the end of this report)
Sequence 2509906, US/10940892 US20050255487
GENERAL INFORMATION
APPLICANT: Dharmacon, Inc.
APPLICANT: Khvorova, Anastasia
APPLICANT: Reynolds, Angela
APPLICANT: Leake, Devin
APPLICANT: Marshall, William
APPLICANT: Read, Steven
APPLICANT: Scaringe, Stephen
TITLE OF INVENTION: Methods and Compositions for Improving
TITLE OF INVENTION: siRNA Functionality
FILE REFERENCE: 13608PCT
CURRENT APPLICATION NUMBER: US/10/940,892
CURRENT FILING DATE: 2004-09-14
NUMBER OF SEQ ID NOS: 2675299
SEQ ID NO 2509906
LENGTH: 19
TYPE: DNA
ORGANISM: Homo sapiens
FEATURE:
NAME/KEY: misc_RNA
LOCATION: (1)...(19)
OTHER INFORMATION: siRNA sense strand
Query Match 100.0%; Score 19; Length 19;
Best Local Similarity 73.7%;
Matches 14; Conservative 5; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AAGUCCAUCGACAUGUUGC 19
|||:|||:|||||:|::||
Db 19 AAGTCCATCGACATGTTGC 1
RESULT 2
US-10-940-892-2509906
(NOTE: this sequence has 8 duplicates in the database searched.
See complete list at the end of this report)
Sequence 2509906, US/10940892 20050255487
GENERAL INFORMATION
APPLICANT: Dharmacon, Inc.
APPLICANT: Khvorova, Anastasia
APPLICANT: Reynolds, Angela
APPLICANT: Leake, Devin
APPLICANT: Marshall, William
APPLICANT: Read, Steven
APPLICANT: Scaringe, Stephen
TITLE OF INVENTION: Methods and Compositions for Improving
TITLE OF INVENTION: siRNA Functionality
FILE REFERENCE: 13608PCT
CURRENT APPLICATION NUMBER: US/10/940,892
CURRENT FILING DATE: 2004-09-14
NUMBER OF SEQ ID NOS: 2675299
SEQ ID NO 2509906
LENGTH: 19
TYPE: DNA
ORGANISM: Homo sapiens
FEATURE:
NAME/KEY: misc_RNA
LOCATION: (1)...(19)
OTHER INFORMATION: siRNA sense strand
Query Match 100.0%; Score 19; Length 19;
Best Local Similarity 100.0%;
Matches 19; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GCAACAUGUCGAUGGACUU 19
|||||||||||||||||||
Db 1 GCAACAUGUCGAUGGACUU 19
Conclusion
Certain papers related to this application may be submitted to Art Unit 1637 by facsimile transmission. The faxing of such papers must conform with the notices published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 C.F.R. ' 1.6(d)). The official fax telephone number for the Group is 571-273-8300. NOTE: If Applicant does submit a paper by fax, the original signed copy should be retained by applicant or applicant's representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED so as to avoid the processing of duplicate papers in the Office.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jane Zara whose telephone number is (571) 272-0765. The examiner’s office hours are generally Monday-Friday, 10:30am - 7pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jennifer Dunston, can be reached on (571)-272-2916. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (703) 308-0196.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
Jane Zara
9-29-25
/JANE J ZARA/Primary Examiner, Art Unit 1637