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 .
Detailed Action
This action is in response to the papers filed November 19, 2025.
Election/Restrictions
Applicant’s reply filed 11/19/2025 to the Requirement for Restriction/Election mailed 09/19/2025 is acknowledged.
Applicant elected without traverse a Cas9 nuclease and cancer cells, as the type of cells having sequence variation.
Claim Amendments
Applicant’s amendment to the claims filed 11/19/2025 is acknowledged.
Claims 44-60 are pending and under examination.
Priority
The instant application 17/911,018 was filed on 09/12/2022. This application is a national stage of international application PCT/KR2021/003109 filed 03/12/2021, claiming priority based on Korean patent application KR10-2020-0030473 filed 03/12/2020.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. While a certified copy of the foreign patent application is provided with the instant application, a certified English translation of said foreign patent application has not been provided.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 09/12/2022, 08/15/2023, 01/12/2024 and 05/14/2025 have been considered.
Sequence Compliance
Appropriate action is required so that the sequences disclosed in the specification comply with the sequence rules as discussed in MPEP 2421, MPEP 2422, and 37 CFR 1.821 through 1.825.
Pages 170, 171 and 173 of the specification fail to comply with the sequence rules.
The sequence rules embrace all unbranched nucleotide sequences with ten or more nucleotide bases and all unbranched, non-D amino acid sequences with four or more amino acids, provided that there are at least 10 "specifically defined" nucleotides or 4 "specifically defined" or amino acids. The rules apply to all sequences in a given application, whether claimed or not. All such sequences are relevant for the purposes of building a comprehensive database and properly assessing prior art. It is therefore essential that all sequences, whether only disclosed or also claimed, be included in the database. See MPEP 2421.02.
Where a sequence is presented in a drawing, reference must be made to the sequence by use of the sequence identifier, either in the drawing or in the Brief Description of the Drawings, where the correlation between multiple sequences in the drawing and their sequence identifiers in the Brief Description is clear.
Applicant should carefully review the entire specification to ensure compliance with the sequence rules. Applicant should provide a corresponding sequence identifier (SEQ ID NO) with every appearance of a sequence embraced by the sequence rules. If a sequence embraced by the sequence rules is lacking a corresponding sequence identifier (SEQ ID NO) in the instant Sequence Listing, Applicant should provide the sequence in a substitute computer readable form (CRF) copy and a substitute paper copy of the Sequence Listing, as an amendment specifically directing its entry into the application. Applicant should also provide a statement that the content of the paper and computer readable copies are the same and, where applicable, include no new matter, as required by 37 C.F.R.1.821(e) or 1.821(f) or 1.821(g) or 1.825(b) or 1.825(d). Applicant should provide a statement indicating any changes made to the Sequence Listing. Appropriate action is required in reply to this Office action. See attached PTO-2301.
Specification
The disclosure is objected to because of the following informalities:
The disclosure is objected to because it fails to comply with the sequence rules, as noted above.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. See paragraph 484. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
37 CFR 1.52 and 1.58 require all papers, other than drawings, that are submitted on paper or by facsimile transmission, and are to become a part of the permanent United States Patent and Trademark Office records in the file of a patent application or reexamination or supplemental examination proceeding, must be (i) plainly and legibly written either by a typewriter or machine printer in permanent dark ink or its equivalent and (ii) presented in a form having sufficient clarity and contrast between the paper and the writing thereon to permit the direct reproduction of readily legible copies in any number by use of photographic, electrostatic, photo-offset, and microfilming processes and electronic capture by use of digital imaging and optical character recognition. In this case, the Tables on pages 155, 170, 171 and 173 fail to comply with one or more of these requirements. Applicant should amend the identified Tables to remove the shading/ background color from each cell in the Tables. Tables should be presented in black-and-white only and without grayscale.
Appropriate action is required.
Claim Objections
Claim 55 is objected to because of the following informalities:
In claim 55, the phrase “through viral vector” should be “through a viral vector” instead.
Appropriate action is required.
Claim Rejections - 35 USC § 102
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.
Claims 44-60 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 2017/0114413 A1 to Hahn et al.
Hahn relates to compositions and methods for targeting cancer-specific DNA sequences, such as copy number amplifications and other types of cancer-specific variations, such as cancer-specific polymorphisms, insertions or deletions, and methods of treating cancer by administration of such sequence-specific DNA targeting agents. See Abstract.
The method of treating cancer in a subject comprises:
preparing a DNA targeting agent by identifying a cancer cell-specific sequence variation from sequencing a tumor sample obtained from the subject, wherein the DNA targeting agent is a CRISPR/Cas system comprising a Cas nuclease and guide RNA (gRNA); and
administering at least one composition comprising the DNA targeting agent to the subject.
See, e.g., paragraphs 14, 31-33, 38-39, 44-45, 72-76, 79-80, 83-84, 98, 123-125, 132.
The cancer-specific sequence variation refers to a DNA sequence which is specific for cancer cells and does not occur in non-cancerous cells (par. 125, 132), and the DNA targeting agent generates double-strand breaks which may induce cell cycle arrest or cell death, such as apoptosis (par. 123-124). Hahn suggests that targeting cancer-specific sequences may lead to an intolerable level of DNA damage burden in cancer cells, resulting in mitotic catastrophe with resultant cell cycle arrest or cell death (par. 11).
Accordingly, with respect to claim 44, Hahn is found to teach or fairly suggest a method for treating a cancer of a subject, comprising:
obtaining a sample form the subject, wherein the sample comprises at least cancer cells of the subject;
obtaining sequencing information from the sample;
identifying multiple mutated sequences of the cancer cell which are not found in a normal cell from the sequencing information;
selecting at least a part of the identified mutated sequences;
preparing a composition comprising a Cas protein and a guide RNA, wherein the guide RNA is complementary to the selected mutated sequences; and
administering the composition to the subject, whereby the Cas protein and guide RNA induces double strand breaks in the genomic DNA of the cancer cells, resulting in selective death of the cancer cells.
Claim 44 further recites that the composition comprises 6-30 guide RNAs, wherein each of the multiple guide RNAs is complementary to the selected multiple mutated sequences.
"[W]hen, as by a recitation of ranges or otherwise, a claim covers several compositions, the claim is ‘anticipated’ if one of them is in the prior art." Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (citing In re Petering, 301 F.2d 676, 682, 133 USPQ 275, 280 (CCPA 1962)) (emphasis in original) (Claims to titanium (Ti) alloy with 0.6-0.9% nickel (Ni) and 0.2-0.4% molybdenum (Mo) were held anticipated by a graph in a Russian article on Ti-Mo-Ni alloys because the graph contained an actual data point corresponding to a Ti alloy containing 0.25% Mo and 0.75% Ni and this composition was within the claimed range of compositions.). "If the prior art discloses a point within the claimed range, the prior art anticipates the claim." UCB, Inc. v. Actavis Labs. UT, Inc., 65 F.4th 679, 687, 2023 USPQ2d 448 (Fed. Cir. 2023). See MPEP 2131.03.
In this case, Hahn teaches that the subject may be administered two or more compositions, wherein each composition targets a different cancer-specific DNA sequence variation. The method may involve a multiplexed DNA targeting agent, wherein at least 2, 3, 4, 5, 6, 7, 8, 9, 10 or more different DNA targeting agents, each targeting a different cancer-specific sequence variation, is used. See paragraphs 73, 143. Therefore, since the DNA targeting agent is a CRISPR/Cas system comprising a Cas nuclease and guide RNA, Hahn is found to teach or fairly suggest the composition comprises, at least, 6, 7, 8, 9 or 10 different guide RNAs, each complementary to different mutated sequences. Accordingly, the claimed range of 6-30 guide RNAs, as claimed in claim 44, is anticipated by Hahn.
For these reasons, claim 44 is anticipated by Hahn.
Regarding dependent claim 45, Hahn teaches or fairly suggests that the sequencing information is obtained by performing next-generation sequencing on the sample. See, e.g., par. 90, 126, and fig. 1A.
Regarding dependent claims 46-47, 54, 57-60, Hahn is found to teach or fairly suggest the composition comprises, at least, 6, 7 or 8 different guide RNAs, each complementary to different mutated sequences, as discussed above. See paragraphs 73, 143. Further, as discussed above, cell death of the cancer cell is induced by double strand breaks generated by the CRISPR/Cas system, as claimed in claim 54. See paragraphs 11, 123-124.
Regarding dependent claims 48-49, Hahn teaches or fairly suggests that the Cas protein is a Cas9 protein derived from Streptococcus thermophilus or pyogenes. See, e.g., par. 14, 49, 176.
Regarding dependent claims 50-53, and 55, Hahn teaches or fairly suggests the composition comprises a Cas protein complexed with the guide RNA, the Cas protein and/or guide RNA is encoded by a nucleic acid, and/or the CRISPR/Cas system is delivered to the subject via a viral vector or nanoparticle. See, e.g., paragraphs 217, 256, 278, 296-297.
Regarding dependent claim 56, Hahn teaches or fairly suggests the cancer is sarcoma, colon cancer or lung cancer. See paragraph 80.
For these reasons, dependent claims 45-60 are also anticipated by Hahn.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 44-56 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending U.S. Application No. 17/276,090 (reference to claim listing filed 05/13/2025). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims anticipate the instant claims. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The reference claims recite a method of treating cancer of a subject comprising:
obtaining a sample from the subject, wherein the sample comprises at least cancer cells of the subject;
obtaining sequencing information from the sample;
identifying multiple mutated sequences of the cancer cell which are not found in a normal cell from the sequencing information;
selecting at least a part of the identified multiple mutated sequences;
preparing a composition comprising a Cas9 protein or a nucleic acid encoding the Cas9 protein, and multiple guide RNAs or nucleic acid encoding the multiple guide RNAs, wherein each of the multiple guide RNAs is complementary to the selected multiple mutated sequences; and
administering the composition to the subject, whereby the Cas protein and the multiple guide RNAs induce multiple double strand breaks in a genomic DNA of the cancer cells, which selectively induce death of the cancer cell. See claim 66.
The reference claims further recite that the cancer cell is a lung cancer cell, colon cancer cell or osteosarcoma cell (claim 67); the sequencing information is obtained by performing next-generation sequencing on the sample (claim 68); the cancer cell comprises at least ten mutated sequences, the number of the selected multiple mutated sequences that are targeted by the multiple guide RNAs is at least ten, the number of multiple guide RNAs is at least ten, and cell death is induced by at least ten double strand breaks in the genomic DNA of the cancer cell (claims 69-70, 77, 79); the Cas9 protein is derived from Streptococcus pyogenes, Streptococcus thennophilus, Staphylococcus aureus, or Campylobacter jejuni (claim 71); the composition comprises a ribonucleoprotein (RNP) in which the Cas9 protein is complexed with each of the multiple guide RNAs (claim 72); the Cas9 protein and/or multiple guide RNAs is encoded by a nucleic acid (claims 73-75); the composition is delivered via a viral vector or nanoparticles (claims 76-77, 80).
For these reasons, the reference claims anticipate instant claims 44-56.
Claim 57-60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending U.S. Application No. 17/276,090, as applied to claims 44-56 above, because the instant claims would have been prima facie obvious over the reference claims.
The reference claims recite the cancer cell comprises at least ten mutated sequences, the number of the selected multiple mutated sequences that are targeted by the multiple guide RNAs is at least ten, the number of multiple guide RNAs is at least ten, and cell death is induced by at least ten double strand breaks in the genomic DNA of the cancer cell (claims 69-70, 77, 79).
The reference claims do not recite that the composition comprises 6, 7 or 8 guide RNAs with different sequences or nucleic acids encoding the guide RNAs, as instantly claimed in claims 57-60.
"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). In this case, the instant claims recite a composition comprising 6, 7 or 8 different guide RNAs, and the reference claims recite a composition comprising at least 10 different guide RNAs. The guide RNAs target the cancer-specific mutations for Cas nucleases to induce double-strand breaks, resulting in cell death or apoptosis. Accordingly, one of ordinary skill in the art would have recognized that the number of guide RNAs is a result-effective variable influencing the amount of damage made to the genomic DNA of the cancer cells, which causes the desired cell death. Therefore, prior to the effective filing date of the instantly claimed invention, one of ordinary skill in the art would have been led to modify the number of guide RNAs through routine optimization in order to improve upon the invention of the reference claims, e.g., by making a more efficient composition while maintaining an effective level of genomic DNA damage.
For these reasons, the limitations of instant claims 57-60 would have been prima facie obvious over the reference claims.
Claims 44-56 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending U.S. Application No. 19/288,975 (reference to claim listing filed 08/01/2025). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims anticipate the instant claims. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The reference claims recite a method of treating cancer of a subject comprising:
obtaining a sample from the subject, wherein the sample comprises at least cancer cells of the subject;
obtaining sequencing information from the sample;
identifying multiple mutated sequences of the cancer cell which are not found in a normal cell from the sequencing information;
selecting at least a part of the identified multiple mutated sequences;
preparing a composition comprising a Cas9 protein or a nucleic acid encoding the Cas9 protein, and multiple guide RNAs or nucleic acid encoding the multiple guide RNAs, wherein each of the multiple guide RNAs is complementary to the selected multiple mutated sequences; and
administering the composition to the subject, whereby the Cas protein and the multiple guide RNAs induce multiple double strand breaks in a genomic DNA of the cancer cells, which selectively induce death of the cancer cell. See claim 1.
The reference claims further recite that the cancer cell is a lung cancer cell, colon cancer cell or osteosarcoma cell (claim 2); the sequencing information is obtained by performing next-generation sequencing on the sample (claim 3); the cancer cell comprises at least ten mutated sequences, the number of the selected multiple mutated sequences that are targeted by the multiple guide RNAs is at least ten, the number of multiple guide RNAs is at least ten, and cell death is induced by at least ten double strand breaks in the genomic DNA of the cancer cell (claims 4-5, 13-14); the Cas9 protein is derived from Streptococcus pyogenes, Streptococcus thennophilus, Staphylococcus aureus, or Campylobacter jejuni (claim 6); the composition comprises a ribonucleoprotein (RNP) in which the Cas9 protein is complexed with each of the multiple guide RNAs (claim 7); the Cas9 protein and/or multiple guide RNAs is encoded by a nucleic acid (claims 8-10); the composition is delivered via a viral vector or nanoparticles (claims 11-12, 15).
For these reasons, the reference claims anticipate instant claims 44-56.
Claim 57-60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending U.S. Application No. 19/288,975, as applied to claims 44-56 above, because the instant claims would have been prima facie obvious over the reference claims.
The reference claims recite the cancer cell comprises at least ten mutated sequences, the number of the selected multiple mutated sequences that are targeted by the multiple guide RNAs is at least ten, the number of multiple guide RNAs is at least ten, and cell death is induced by at least ten double strand breaks in the genomic DNA of the cancer cell (claims 4-5, 13-14).
The reference claims do not recite that the composition comprises 6, 7 or 8 guide RNAs with different sequences or nucleic acids encoding the guide RNAs, as instantly claimed in claims 57-60.
"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). In this case, the instant claims recite a composition comprising 6, 7 or 8 different guide RNAs, and the reference claims recite a composition comprising at least 10 different guide RNAs. The guide RNAs target the cancer-specific mutations for Cas nucleases to induce double-strand breaks, resulting in cell death or apoptosis. Accordingly, one of ordinary skill in the art would have recognized that the number of guide RNAs is a result-effective variable influencing the amount of damage made to the genomic DNA of the cancer cells, which causes the desired cell death. Therefore, prior to the effective filing date of the instantly claimed invention, one of ordinary skill in the art would have been led to modify the number of guide RNAs through routine optimization in order to improve upon the invention of the reference claims, e.g., by making a more efficient composition while maintaining an effective level of genomic DNA damage.
For these reasons, the limitations of instant claims 57-60 would have been prima facie obvious over the reference claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAMES J GRABER whose telephone number is (571)270-3988. The examiner can normally be reached Monday-Thursday: 9:00 am - 4:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James D Schultz can be reached at (571)272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JAMES JOSEPH GRABER/Examiner, Art Unit 1631