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
Election/Restrictions
Applicant's election without traverse of Group I, claims 74-85, in the reply filed on 04/02/2026 is acknowledged. New Claims 94-103 have been added and are within the scope of the elected claims.
Status of the Application
Claims 74, 75, 77-81, 83-85 and 94-103 are pending and currently under examination. Claims 1-73, 76, 82 and 86-93 have been canceled. SEQ ID Nos. 3 and 62 are free of the prior art searched.
Sequence Disclosures Filed On Or After July 1, 2022
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
There are skipped sequences for SEQ ID Nos. 2 and 5 in the Sequence Listing filed 09/14/2023 which are prohibited. SEQ ID Nos. 2 and 5 are sequences having 7 amino acids and therefore are required in the sequence listing in view of WIPO ST.26 rules. Applicant should amend the specification to replace all relevant SEQ ID NOs with the actual sequences, if originally disclosed.
Specification Objections
The disclosure is objected to because it refers to different sequences that are not in the sequence listing filed 09/14/2023. Specifically Table 1 refers to SEQ ID Nos. 2 and 5 as amino acid sequences however the sequence listing does not have a sequence for these SEQ ID Nos. Applicant is required to correct these errors. This is not an extensive search for all instances of missing sequences in the specification and Applicant is encouraged to review the specification and make corrections if appropriate.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Paragraph [0056] lists hyperlinks and/or other forms of browser-executable code. 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.
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 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.
Claim(s) 74, 83, 85 and 99-103 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Liu et al. ("CRISPR-Cas9-mediated multiplex gene editing in CAR-T cells." Cell research 27.1 (2017): 154-157).
Liu et al. teach a method of editing multiple genes in CAR-T cells comprising introducing a Cas9 nuclease and guide RNAs engineered to target two (TRAC and B2M) or three genes (TRAC, B2M and PD-1) each configured to specifically target each target loci (see page 154 and 155), wherein the editing was quantified by tracking of indels (page 154 last para.).
Thus Liu et al. anticipates the instant claims.
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 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 77, 94, 95 and 98 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. ("CRISPR-Cas9-mediated multiplex gene editing in CAR-T cells." Cell research 27.1 (2017): 154-157) and Thomas et al. (Patent 10,982,200).
Liu et al. teach a method of editing multiple genes in CAR-T cells comprising introducing a Cas9 nuclease and guide RNAs engineered to target two (TRAC and B2M) or three genes TRAC, B2M and PD-1) each configured to specifically target each target loci (see page 154 and 155), wherein the editing was quantified by tracking of indels (page 154 last para.). Liu et al. do not teach SEQ ID No. 4.
Regarding claims 77, 94 and 95, Thomas et al. teach an engineered nuclease having SEQ ID No. 423 which is 100% identical to SEQ ID No. 4 (see alignment below).Thomas et al. teach this sequence is an endonuclease MG3-8 as described in the instant specification and is capable of targeted endonuclease activity when used in a CRISPR system (see instant specification 87-88). It would have been obvious to use this endonuclease in the method taught by Liu et al. for gene editing given Thomas et al. demonstrates this endonuclease and sequences having at least 85% identical to the nuclease as capable of gene editing.
Regarding claim 98, Thomas et al. teach a sgRNA having SEQ ID No. 5539 that is capable of being used in a CRISPR system (col 4) wherein this sequence is identical to instantly claimed SEQ ID No. 6. It would have been obvious to use this sgRNA to target a gene in the method taught by Liu et al. for gene editing given Thomas et al. demonstrates this sgRNA having at least 85% identical to the nuclease as capable of gene editing.
Thus in the absence of evidence to the contrary, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed.
Claims 84 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. ("CRISPR-Cas9-mediated multiplex gene editing in CAR-T cells." Cell research 27.1 (2017): 154-157) and Duchateau et al. (Patent 9,890,393).
Liu et al. teach a method of editing multiple genes in CAR-T cells comprising introducing a Cas9 nuclease and guide RNAs engineered to target two (TRAC and B2M) or three genes TRAC, B2M and PD-1) each configured to specifically target each target loci (see page 154 and 155), wherein the editing was quantified by tracking of indels (page 154 last para.). Liu et al. do not teach SEQ ID No. 10.
Regarding claim 84, Duchateau et al. teach CRISPR-Cas9 systems targeting genes in CAR T cells and teach a target sequence for a Cas9 in T cells having SEQ ID No. 52 that has 100% sequence identity to SEQ ID No. 10. It would have been obvious for one of skill in the art to use this known sequence in methods of targeting a gene in T cells in efforts to edit genes.
Thus in the absence of evidence to the contrary, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed.
Claim Rejections - 35 USC § 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 74, 75, 77, 78, 80, 83-85 and 94-103 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious" and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966; Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include: (1) Actual reduction to practice, (2) Disclosure of drawings or structural chemical formulas, (3) Sufficient relevant identifying characteristics (such as: i. Complete structure, ii. Partial Structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with a known or disclosed structure, and v. Correlation between function and structure), (4) Method of making the claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art.
Moreover, the written description requirement for a genus may be satisfied through sufficient description of a representative number of species by “…disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between functional and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.” Thus when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
The claims are drawn to a genus of:
first class 2 type II Cas endonucleases, second class 2 type II Cas endonucleases, first and second gRNA and spacer sequences,
first class 2 type II Cas endonucleases encoded by a nucleic acid comprising at least 75% sequence identity to SEQ ID No. 62,
second class 2 type II Cas endonucleases comprising a sequence having at least 75% sequence identity to SEQ ID No. 4,
first engineered guide ribonucleic acid comprising a sequence of 80% SEQ ID NO. 3,
first spacer sequences having at least 80% sequence identity to SEQ ID No. 10 and
second engineered guide ribonucleic acid comprising a sequence of 80% SEQ ID NO. 6,
with the function of multiplex editing in any cell.
When determining whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. In the instant case, the specification describes a first class 2 type II Cas endonuclease encoding by a nuclease having SEQ ID No. 62 and a second class 2 type II Cas endonucleases having a sequence of SEQ ID No. 4, a first and second engineered guide ribonucleic acid having SEQ ID Nos. 3 and 6 and a spacer having SEQ ID No. 10 in Table 1. The specification does not describe the vast number of different types and sized nucleic acid and amino acid sequences as claimed, including using the claimed sequences of a first or second endonucleases and any number of different gRNA sequences or known gRNA sequences and unknown endonucleases, with the function of multiplex editing in any cell.
It is then determined whether a representative number of species have been sufficiently described by other relevant identifying characteristics (i.e. other than a nucleotide sequence or endonuclease sequences), specific features and functional attributes that would distinguish different members of the claimed genus. In the instant case, the specification describes SpCas9 sequences, sgRNA sequences that target two loci with the function of editing these genes in T cells (Example 3-5). These functional limitations cannot be identifying characteristics for the vast number of nucleic acids and types of endonuclease sequences claimed. The disclosure has not described any of the sequences having at least 75% sequence identity to SEQ ID No. 62, at least 75% sequence identity to SEQ ID No. 4, a sequence of 80% SEQ ID NO. 3 sequences having at least 80% sequence identity to SEQ ID No. 10 or a sequence of 80% SEQ ID NO. 6 used in methods with the claimed function. The disclosure has not described any class 2 type II Cas endonuclease or any gRNA with the claimed function of multiplex gene editing. A review of the specification shows that it provides no description or guidance that would allow one of skill to distinguish the functional species of the recited structural genus from the non-functional members without empirical determination.
The prior art does not appear to provide written description to support the broad genus of Cas proteins. The prior art of Koonin et al. ("Diversity, classification and evolution of CRISPR-Cas systems." Current opinion in microbiology 37 (2017): 67-78) teach there are numerous different Cas proteins from numerous different organisms (see Figure 1). Koonin et al. illustrates each has different structures based on the different class systems (see Figure 1 and Figure 3). The prior art teaches that the PAM sequence recognized by a Cas protein, such as Cas9, must be determined experimentally for each protein variant (Karvelis et al. Methods, Vol. 121-122, pages 3-8, March 24, 2017; e.g., Abstract). The prior art teaches that orthologs of a single type of Cas protein, such as Cas9, do not all share a common PAM sequence (Seebeck et al. US Patent Application Publication No. 2019/0249200 A1; e.g., Table A and Fig. 1).
Thus the prior art does not teach functional characteristics coupled with a known or disclosed correlation between functional and structure of Cas proteins. Since the disclosure and the prior art fail to describe the common attributes and characteristics concisely identifying members of the proposed genus, and because the claimed genus is highly variant a vast number of nucleic acid sequences and endonuclease sequences, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus claimed.
"A sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can "visualize or recognize" the members of the genus" (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69) (emphasis added). The specification has neither.
Further, “Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features.” Ex parte Kubin, 83 USPQ2d 1410, 1417 (Bd. Pat. App. & Int. 2007) citing University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, 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.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP 2163. The MPEP does state that for generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP 2163. Although the MPEP does not define what constitute a sufficient number of representative, the Courts have indicated what do not constitute a representative number species to adequately describe a broad generic. In Gosteli, the Court determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gosteli, 872 F.2d at 1012, 10 USPQ2d at 1618.
Thus the specification and claims lack written description because it is clear that Applicant did not have possession of every variation of nucleotide sequences and endonuclease sequences. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521,222 USPQ 369,372-372 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventors, at the time the application was filed, had possession of the entire scope of the claimed invention.
Enablement
Claims 74, 75, 77-81, 83-85 and 94-103 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 methods of editing two and three different loci using MG3-6 Cas 9 endonuclease with specific sgRNA targeted to the different loci,
does not reasonably provide enablement for methods of editing two or more loci using the vast number of differently sized and types of class 2 type II Cas endonucleases and different guide RNA. 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 use the invention commensurate in scope with these claims.
The following factors have been considered in the analysis of enablement: (1) the breadth of the claims, (2) the nature of the invention, (3) the state of the prior art, (4) the level of one of ordinary skill, (5) the level of predictability in the art, (6) the amount of direction provided by the inventor, (7) the existence of working examples, (8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The breadth of the claims and the nature of the invention:
The broadest reasonable interpretation of the claimed method is editing two or more different loci in any cell using a vast number of different class 2 type II Cas endonuclease sequences and differently sized gRNA to any target.
Whether the specification would have been enabling as of the filing date involves consideration of the nature of the invention, the state of the prior art, and the level of skill in the art. The state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains. The relative skill of those in the art refers to the skill of those in the art in relation to the subject matter to which the claimed invention pertains at the time the application was filed. See MPEP § 2164.05(b). The state of the prior art provides evidence for the degree of predictability in the art and is related to the amount of direction or guidance needed in the specification as filed to meet the enablement requirement. The state of the prior art is also related to the need for working examples in the specification.
The state of the prior art:
Enbo et al. ("Single-stranded DNA cleavage by divergent CRISPR-Cas9 enzymes." Molecular cell 60.3 (2015): 398-407 of record cited on 892 mailed 11/18/2024) describes divergent class 2 type II Cas9 enzymes and illustrates how each are structurally different (see Figure B below). Enbo et al. further highlights the differences in cleavage activity between different Cas9 enzymes in Figure E below.
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Enbo et al. describes each of these enzymes has different cleavage abilities (see Fig. 1E and 4) and teach distinct Cas9 cleavage activities correlate with protein size and architecture. Structural and biochemical studies indicate that the type II-A Spy Cas9 undergoes a large conformational rearrangement upon guide RNA binding, with additional changes upon dsDNA target recognition (see discussion page 405 second para.).
A review of the prior art does not predictably provide evidence that using any size and type of endonuclease along with any gRNA can be used to edit any number of loci in any cell.
The level of one of ordinary skill:
While the level of one of ordinary skill practicing said invention would be high, the level of predictability is considered variable as evident in the prior art discussed above and is not considered to provide sufficient enablement to practice the claimed invention.
Because the state of the prior art does not provide evidence of the degree of predictability that methods for editing two or more loci using any type of lass 2 type II Cas endonuclease and gRNA, one of ordinary skill in the art would look for guidance or direction in the instant specification.
The level of predictability in the art:
“The “predictability or lack thereof” in the art refers to the ability of one skilled in the art to extrapolate the disclosed or known results to the claimed invention. If one skilled in the art can readily anticipate the effect of a change within the subject matter to which the claimed invention pertains, then there is predictability in the art. On the other hand, if one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art. Accordingly, what is known in the art provides evidence as to the question of predictability.” (MPEP 2164.03).
The amount of direction provided by the inventor:
The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount of guidance or direction” refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling. >See, e.g., Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1326 (Fed. Cir. 2004).
The existence of working examples:
The working embodiment in the instant application describes using methods of editing two and three different loci using MG3-6 Cas 9 endonuclease with specific sgRNA targeted to the different loci. The working embodiments do not describe the method using the vast number of different endonuclease and gRNA sequences.
The standard of an enabling disclosure is not the ability to make and test if the invention works but one of the ability to make and use with a reasonable expectation of success. A patent is granted for a completed invention, not the general suggestion of an idea (MPEP 2164.03 and Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1325-26 (Fed. Cir. 2004). The instant invention suggests methods of editing two or more loci in a cell without an enabling disclosure or guidance in the prior art describing how to make or use any number of different endonuclease and sgRNA sequences.
While the MPEP 2164.02 states the specification need not contain an example if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation. In re Borkowski, 422 F.2d 904, 908, 164 USPQ 642, 645 (CCPA 1970), the lack of a working example, however, is a factor to be considered, especially in a case involving an unpredictable and undeveloped art.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure:
The prior art is undeveloped for the role all the different sequences and functions to class 2 type II Cas nucleases plays in gene editing along with different sequences of gRNA and without further guidance, one of skill in the art would have to practice a substantial amount of trial and error experimentation, an amount considered undue and not routine, to practice the instantly claimed invention.
Sequence Alignments
Patent No. 10982200
GENERAL INFORMATION
APPLICANT: METAGENOMI IP TECHNOLOGIES, LLC
SEQ ID NO 423
LENGTH: 1132
OTHER INFORMATION: MG3-8 effector
Query Match 100.0%; Score 5816; Length 1132;
Best Local Similarity 100.0%;
Matches 1132; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
QY – SEQ ID No. 4
DB – SEQ ID NO. 423
Qy 1 MSTDMKNYRIGVDVGDRSVGLAAIEFDDAGFPIQKLALVTFRHDGGLDPTDNPKSRKETR 60
Db 1 MSTDMKNYRIGVDVGDRSVGLAAIEFDDAGFPIQKLALVTFRHDGGLDPTDNPKSRKETR 60
Qy 61 GEARRRMRMTRRRKQRLRDLDKVLENLGYTVPEGPEPETYEAWTSRALLASIKLASADEL 120
Db 61 GEARRRMRMTRRRKQRLRDLDKVLENLGYTVPEGPEPETYEAWTSRALLASIKLASADEL 120
Qy 121 NEHLVRAVRHIARHRGWVNPWWSLDQLERASQEPSETFEIILARARELFGERVPANPTLG 180
Db 121 NEHLVRAVRHIARHRGWVNPWWSLDQLERASQEPSETFEIILARARELFGERVPANPTLG 180
Qy 181 MLGALAANNEVLLRPRAEKKKKTGYVRGTPLLAAQVRQIDQVAELRRICEVQGIEEQYET 240
Db 181 MLGALAANNEVLLRPRAEKKKKTGYVRGTPLLAAQVRQIDQVAELRRICEVQGIEEQYET 240
Qy 241 LRNAIFAHKVAYVPTERVGKDPLAPSKNRTIRASLEFQEFRILDSVANLRVRTDSRAKRE 300
Db 241 LRNAIFAHKVAYVPTERVGKDPLAPSKNRTIRASLEFQEFRILDSVANLRVRTDSRAKRE 300
Qy 301 LTEGEYDAAVEFLMGYTAKEQPSWADVAEEIGVPGNRLIAPVLEDVQQKTAPFDRSSAAF 360
Db 301 LTEGEYDAAVEFLMGYTAKEQPSWADVAEEIGVPGNRLIAPVLEDVQQKTAPFDRSSAAF 360
Qy 361 EKAMSKRTEARQWWEANDDDQLRSLFIMFLADATNDTEEAAAVAGLPELYMSWPAEEREA 420
Db 361 EKAMSKRTEARQWWEANDDDQLRSLFIMFLADATNDTEEAAAVAGLPELYMSWPAEEREA 420
Qy 421 LSNIDFEKGRVAYSHETLSKLSEYMHEHRVGLHEARKAVFGVDDTWRPPLAKLEEPTGQP 480
Db 421 LSNIDFEKGRVAYSHETLSKLSEYMHEHRVGLHEARKAVFGVDDTWRPPLAKLEEPTGQP 480
Qy 481 TVDRVLTILRRFVLDCERQWGRPRAITVEHARIGLVGPAQRQNILKEQEDNRKNNECIRD 540
Db 481 TVDRVLTILRRFVLDCERQWGRPRAITVEHARIGLVGPAQRQNILKEQEDNRKNNECIRD 540
Qy 541 ELRKSGVENPSRTEVRRHLVVQDQESQCLYCGAVIRTDTSELDHIVPRAGGGSSRRENLA 600
Db 541 ELRKSGVENPSRTEVRRHLVVQDQESQCLYCGAVIRTDTSELDHIVPRAGGGSSRRENLA 600
Qy 601 AVCRYCNSKKDRTLFYDWAGSVRLQETIDRVRQLKAFKDSKKAKMFKNQIRRLRQTEADE 660
Db 601 AVCRYCNSKKDRTLFYDWAGSVRLQETIDRVRQLKAFKDSKKAKMFKNQIRRLRQTEADE 660
Qy 661 PIDERSLASTSYAAVAVRERLEQHFNEGLAPDDKNRVVLDVYAGSVTRESRRAGGIDERI 720
Db 661 PIDERSLASTSYAAVAVRERLEQHFNEGLAPDDKNRVVLDVYAGSVTRESRRAGGIDERI 720
Qy 721 LLRGERDKNRFDVRHHAIDAAVMTLLNRSVALTLEQRSQLRRAFYEQGLDKLDRDQLKPE 780
Db 721 LLRGERDKNRFDVRHHAIDAAVMTLLNRSVALTLEQRSQLRRAFYEQGLDKLDRDQLKPE 780
Qy 781 EDWRNFIGLSLASQEKFLEWKKVTTVLGDLLAEAIEDDSIAVVSPLRLRPQNGRVHKDTI 840
Db 781 EDWRNFIGLSLASQEKFLEWKKVTTVLGDLLAEAIEDDSIAVVSPLRLRPQNGRVHKDTI 840
Qy 841 AAVKKQTLGSAWSADAVKRIVDPEIYLAMKDALGKSKVLPEDSARTLELSDGRYLEADDE 900
Db 841 AAVKKQTLGSAWSADAVKRIVDPEIYLAMKDALGKSKVLPEDSARTLELSDGRYLEADDE 900
Qy 901 VLFFPKNAASILTPRGVAEIGGSIHHARLYSWLTKKGELKIGMLRVYGAEFPWLMRESGS 960
Db 901 VLFFPKNAASILTPRGVAEIGGSIHHARLYSWLTKKGELKIGMLRVYGAEFPWLMRESGS 960
Qy 961 HDVLRMPIHPGSQSFRDMQDTTRKAVESSEAVEFAWITQNDELEFEPEDYIAHGGKDELR 1020
Db 961 HDVLRMPIHPGSQSFRDMQDTTRKAVESSEAVEFAWITQNDELEFEPEDYIAHGGKDELR 1020
Qy 1021 QFLEFMPECRWRVDGFKKNYQIRIRPAMLSREQLPSDIQRRLESKTLTENESLLLKALDT 1080
Db 1021 QFLEFMPECRWRVDGFKKNYQIRIRPAMLSREQLPSDIQRRLESKTLTENESLLLKALDT 108
Qy 1081 GLVVAIGGLLPLGTLKVIRRNNLGFPRWRGNGNLPTSFEVRSSALRALGVEG 1132
Db 1081 GLVVAIGGLLPLGTLKVIRRNNLGFPRWRGNGNLPTSFEVRSSALRALGVEG 1132
Patent No. 10982200
GENERAL INFORMATION
APPLICANT: METAGENOMI IP TECHNOLOGIES, LLC
SEQ ID NO 5539
LENGTH: 110
Query Match 100.0%; Score 88; Length 110;
Best Local Similarity 69.3%;
Matches 61; Conservative 27; Mismatches 0; Indels 0; Gaps 0;
Qy SEQ ID No. 6
Db SEQ ID No. 5539
Qy 23 GTTGAGAATCGAAAGATTCTTAATAAGGCATCCTTCCGATGCTGACTTCTCACCGTCCGG 82
Db 23 GUUGAGAAUCGAAAGAUUCUUAAUAAGGCAUCCUUCCGAUGCUGACUUCUCACCGUCCGG 82
Qy 83 CTCCTCTTAGGAACGGGCGGTATGTTTT 110
Db 83 CUCCUCUUAGGAACGGGCGGUAUGUUUU 110
Patent No. 9890393
GENERAL INFORMATION
APPLICANT: CELLECTIS
PRIOR FILING DATE: 2013-05-29
NUMBER OF SEQ ID NOS: 66
SEQ ID NO 52
LENGTH: 23
Query Match 100.0%; Score 22; Length 23;
Best Local Similarity 100.0%;
Matches 22; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy SEQ ID No. 10
Db SEQ ID No. 52
Qy 1 CGAATCCTCCTCCTGAAAGTGG 22
Db 2 CGAATCCTCCTCCTGAAAGTGG 23
Closest prior art
SEQ ID Nos. 3 and 62 are free of the prior art. SEQ ID No. 3 is described in the instant specification as a MG3-6 sgRNA. The specification describes generating genomic fragments from metagenomes for Type V-A nucleases and generating sgRNA for use in CRISPR-Cas systems (0071). The prior art does not teach or make obvious SEQ ID No. 3 as a sgRNA.
SEQ ID No. 62 is described in the instant specification as a nucleic acid encoding MG3-6 endonuclease. Thomas et al. (Patent 10,982,200) teach a sequence having 60% sequence identity to SEQ ID No. 62 (SEQ ID No. 5590) which is described as a nucleic acid sequence encoding a Cas endonuclease (col. 11). Thomas et al. does not teach the claimed sequence or make obvious reasons to extend the sequence to encompass at least 75% -100% sequence identity to SEQ ID No. 62.
Conclusion
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/KIMBERLY CHONG/
Primary Examiner Art Unit 1636
Prosecution Insights