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The U.S. Apparent and Trademark Office accepted U.S. Apparent No. 10,113,167 today, October 30, 2018, to the University of California/Berkeley, directed to an aspect of its CRISPR technology (where CRISPR is an acronym for Clustered Regularly lnterspaced Short Palindromic Repeats).  The arrest amid the Broad Institute and the University of California/Berkeley over patents directed to CRISPR technology has been in the spotlight over the accomplished few years (see “CRISPR Arrest Declared”; “PTAB Decides CRISPR Arrest — No interference-in-fact”; “PTAB Decides CRISPR Arrest in Favor of Broad Institute — Their Reasoning”; “University of California/Berkeley Appeals Adverse CRISPR Accommodation by PTAB”; and “Berkeley Files Opening Brief in CRISPR Appeal”).  And while the Broad was acknowledged in accepting the Federal Circuit to assert the PTAB’s accommodation that there was no interference-in-fact amid the parties’ claims (see “Regents of the University of California v. Broad Institute, Inc. (Fed. Cir. 2018): Federal Circuit Affirms PTAB in Appeal of CRISPR Interference”) and there accept been letters of the outcomes of added skirmishes amid the parties in the concurrently (see “The CRISPR Chronicles — Broad Institute Wins One and Loses One”), questions abide about how the rights to this technology will be apportioned amid the parties and useful, reliable apparent licenses will be accepted to admittance able-bodied development and accomplishment of the abounding promises of CRISPR in a advanced array of abiogenetic contexts.

The Broad’s all-encompassing apparent portfolio survived the interference, decidedly these patents anon at issue:

• U.S. Apparent No. 8,697,359 — claims 1-20• U.S. Apparent No. 8,771,945 — claims 1-29• U.S. Apparent No. 8,795,965 — claims 1-30• U.S. Apparent No. 8,865,406 — claims 1-30• U.S. Apparent No. 8,871,445 — claims 1-30• U.S. Apparent No. 8,889,356 — claims 1-30• U.S. Apparent No. 8,895,308 — claims 1-30• U.S. Apparent No. 8,906,616 — claims 1-30• U.S. Apparent No. 8,932,814 — claims 1-30• U.S. Apparent No. 8,945,839 — claims 1-28• U.S. Apparent No. 8,993,233 — claims 1-43• U.S. Apparent No. 8,999,641 — claims 1-28

The Berkeley application-in-interference, U.S. Application No. 13/842,859, appear as U.S. Apparent Application Publication No. US 2014/0068797, charcoal in Apparent Office limbo during the pendency of cloister proceedings; these claims accommodate the following:

165.  A adjustment of cleaving a nucleic acerbic absolute contacting a ambition DNA atom accepting a ambition arrangement with an engineered and/or non-naturally-occurring Blazon II Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR associated (Cas) (CRISPR-Cas) arrangement comprising    a) a Cas9 protein; and    b) a distinct atom DNA-targeting RNA comprising        i) a targeter-RNA that hybridizes with the ambition sequence, and        ii) an activator-RNA that hybridizes with the targeter-RNA to anatomy a double-stranded RNA bifold of a protein-binding segment,    wherein the activator-RNA and the targeter-RNA are covalently affiliated to one addition with amid nucleotides,    wherein the distinct atom DNA-targeting RNA forms a circuitous with the Cas9protein,    whereby the distinct atom DNA-targeting RNA targets the ambition sequence, and the Cas9 protein cleaves the ambition DNA molecule.

203.  An engineered and/or non-naturally occurring Blazon II Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR associated (Cas) (CRISPR-Cas) arrangement comprising    a) a Cas9 protein, or a nucleic acerbic absolute a nucleotide arrangement encoding said Cas9 protein; and    b) a distinct atom DNA-targeting RNA, or a nucleic acerbic absolute a nucleotide arrangement encoding said distinct atom DNA-targeting RNA;    wherein the distinct atom DNA-targeting RNA comprises:        i) a targeter-RNA that is able of hybridizing with a ambition arrangement in a ambition DNA molecule, and        ii) an activator-RNA that is able of hybridizing with the targeter-RNA to anatomy a double-stranded RNA bifold of a protein-binding segment,    wherein the activator-RNA and the targeter-RNA are covalently affiliated to one addition with amid nucleotides; and    wherein the distinct atom DNA-targeting RNA is able of basic a circuitous with the Cas9 protein, thereby targeting the Cas9 protein to the ambition DNA molecule,whereby said arrangement is able of cleaving or alteration the ambition DNA atom or modulating archetype of at atomic one gene encoded by the ambition DNA molecule.

224.  A Blazon II Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR associated (Cas) (CRISPR-Cas) arrangement comprising:    a Cas9 protein; and    a distinct atom DNA-targeting RNA, or a nucleic acerbic absolute a nucleotide arrangement encoding said distinct atom DNA-targeting RNA,    wherein the distinct atom DNA-targeting RNA comprises:        i) a targeter-RNA that is able of hybridizing with a ambition arrangement in a ambition DNA molecule, and        ii) an activator-RNA that is able of hybridizing with the targeter-RNA to anatomy a double-stranded bifold of a protein-binding segment,    wherein i) and ii) are abiding in a 5′ to 3′ acclimatization and are covalently affiliated to one addition with amid nucleotides;    wherein the distinct atom DNA-targeting RNA is able of basic a circuitous with the Cas9 protein and admixture of the targeter-RNA to the ambition arrangement is able of targeting the Cas9 protein to the ambition DNA molecule, and    wherein the distinct atom DNA-targeting RNA comprises one or added arrangement modifications compared to a arrangement of a agnate agrarian blazon tracrRNA and/or crRNA.

The ‘167 apparent accepted today, includes the afterward claims:

1.  A non-naturally occurring DNA-targeting RNA, or a nucleic acerbic encoding the non-naturally occurring DNA-targeting RNA, wherein the non-naturally occurring DNA-targeting RNA comprises: (a) a targeter-RNA comprising: (i) a aboriginal nucleotide arrangement that is commutual to a ambition arrangement of a ambition DNA molecule, and (ii) a additional nucleotide arrangement that hybridizes with an activator-RNA, wherein the aboriginal and additional nucleotide sequences are heterologous to one another; and (b) the activator-RNA, which hybridizes with the additional nucleotide arrangement of the targeter-RNA to anatomy a double-stranded RNA (dsRNA) bifold of a protein-binding segment, wherein the activator-RNA hybridizes with the targeter-RNA to anatomy a absolute of 8 to 15 abject pairs, wherein the non-naturally occurring DNA-targeting RNA is able of basic a circuitous with a Cas9 polypeptide and targeting the circuitous to the ambition arrangement of the ambition DNA molecule.

12.  A non-naturally occurring DNA-targeting RNA that comprises: (a) a targeter-RNA absolute a nucleotide arrangement that is commutual to a ambition arrangement of a ambition DNA molecule, and (b) an activator-RNA that hybridizes with the targeter-RNA to anatomy a double-stranded RNA (dsRNA) bifold of a protein-binding segment, wherein the activator-RNA hybridizes with the targeter-RNA to anatomy a absolute of 8 to 15 abject pairs, wherein the non-naturally occurring DNA-targeting RNA comprises one or added of: a non-natural internucleoside linkage, a nucleic acerbic mimetic, a adapted amoroso moiety, and a adapted nucleobase, and wherein the non-naturally occurring DNA-targeting RNA is able of basic a circuitous with a Cas9 polypeptide and targeting the circuitous to the ambition arrangement of the ambition DNA molecule.

19.  One or added nucleic acids encoding a non-naturally occurring DNA-targeting RNA that comprises: (a) a targeter-RNA absolute a nucleotide arrangement that is commutual to a ambition arrangement of a ambition DNA molecule, and (b) an activator-RNA that hybridizes with the targeter-RNA to anatomy a double-stranded RNA (dsRNA) bifold of a protein-binding segment, wherein the activator-RNA hybridizes with the targeter-RNA to anatomy a absolute of 8 to 15 abject pairs, wherein the non-naturally occurring DNA-targeting RNA is able of basic a circuitous with a Cas9 polypeptide and targeting the circuitous to the ambition arrangement of the ambition DNA molecule, and wherein the one or added nucleic acids comprises a aboriginal nucleotide arrangement encoding the targeter-RNA and a additional nucleotide arrangement encoding the activator-RNA; wherein the aboriginal nucleotide sequence, the additional nucleotide sequence, or both, is operably affiliated to a heterologous transcriptional ascendancy arrangement and/or a heterologous translational ascendancy sequence.

36.  A agreement comprising: (1) a non-naturally occurring DNA-targeting RNA, or a nucleic acerbic encoding the non-naturally occurring DNA-targeting RNA, wherein the non-naturally occurring DNA-targeting RNA comprises: (a) a targeter-RNA absolute a nucleotide arrangement that is commutual to a ambition arrangement of a ambition DNA molecule, and (b) an activator-RNA that hybridizes with the targeter-RNA to anatomy a double-stranded RNA (dsRNA) bifold of a protein-binding segment, wherein the activator-RNA hybridizes with the targeter-RNA to anatomy a absolute of 8 to 15 abject pairs, wherein the non-naturally occurring DNA-targeting RNA is able of basic a circuitous with a Cas9 polypeptide and targeting the circuitous to the ambition arrangement of the ambition DNA molecule; and (2) one or added of: a nuclease inhibitor, a buffering agent, a detergent, a polyamine, an adjuvant, a wetting agent, a stabilizing agent, an antioxidant, and a complexing agent.

54.  A agreement comprising: (1) a Cas9 polypeptide, or a nucleic acerbic encoding the Cas9 polypeptide; and (2) a non-naturally occurring DNA-targeting RNA, or a nucleic acerbic encoding the non-naturally occurring DNA-targeting RNA, wherein the non-naturally occurring DNA-targeting RNA comprises: (a) a targeter-RNA comprising: (i) a aboriginal nucleotide arrangement that is commutual to a ambition arrangement of a ambition DNA molecule, and (ii) a additional nucleotide arrangement that hybridizes with an activator-RNA, wherein the aboriginal and additional nucleotide sequences are heterologous to one another; and (b) the activator-RNA, which hybridizes with the additional nucleotide arrangement of the targeter-RNA to anatomy a double-stranded RNA (dsRNA) bifold of a protein-binding segment, wherein the activator-RNA hybridizes with the targeter-RNA to anatomy a absolute of 8 to 15 abject pairs, wherein the non-naturally occurring DNA-targeting RNA is able of basic a circuitous with the Cas9 polypeptide and targeting the circuitous to the ambition arrangement of the ambition DNA molecule.

While the Broad was quicker off the mark in applying for and accepting accepted patents on its flavor(s) of CRISPR, UC/Berkeley has a cardinal of awaiting applications, including U.S. Serial No. 14/942,782, as able-bodied as the afterward eight added applications:

• U.S. Application No. 15/435,233, filed on 2-16-2017, which claims the account of U.S. Application No. 15/138,604;• U.S. Application No. 15/925,544, filed on 3-19-2018, which claims the account of U.S. Application No. 15/138,604;• U.S. Application No. 15/947,700, filed on 4-6-2018, which claims the account of U.S. Application No. 15/138,604;• U.S. Application No. 15/947,718, filed on 4-6-2018, which claims the account of U.S. Application No. 15/138,604;• U.S. Application No. 15/981,808, filed on 5-16-2018, which claims the account of U.S. Application No. 15/138,604;• U.S. Application No. 15/981,809, filed on 5-16-2018, which claims the account of U.S. Application No. 15/138,604;• U.S. Application No. 16/136,159, filed on 9-19-2018, which claims the account of U.S. Application No. 15/138,604; and• U.S. Application No. 16/136,165, filed on 9-19-2018, which claims the account of U.S. Application No. 15/138,604.

Today’s accepted apparent joins ahead accepted U.S. Apparent No. 10,000,772, which contains claims directed to these embodiments of the invention:

1.  A adjustment of modifying a ambition DNA molecule, the adjustment comprising: contacting a ambition DNA atom accepting a ambition arrangement with a circuitous comprising: (a) a Cas9 protein; and (b) a DNA-targeting RNA comprising: (i) a targeter-RNA that hybridizes with the ambition sequence, and (ii) an activator-RNA that hybridizes with the targeter-RNA to anatomy a double-stranded RNA (dsRNA) bifold of a protein-binding segment, wherein the activator-RNA hybridizes with the targeter-RNA to anatomy a absolute of 10 to 15 abject pairs, wherein said contacting takes abode alfresco of a bacterial corpuscle and alfresco of an archaeal cell, thereby consistent in modification of the ambition DNA molecule.

This apparent has eight awaiting accompanying applications:

• U.S. Application No. 15/138,604, filed on 4-26-2016, which claims the account of U.S. Application No. 14/685,502;• U.S. Application No. 15/435,233, filed on 2-16-2017, which claims the account of U.S. Application No. 14/685,502;• U.S. Application No. 15/947,700, filed on 4-6-2018, which claims the account of U.S. Application No. 14/685,502;• U.S. Application No. 16/136,159, filed on 9-19-2018, which claims the account of U.S. Application No. 14/685,502;• U.S. Application No. 15/925,544, filed on 3-19-2018, which claims the account of U.S. Application No. 14/685,502;• U.S. Application No. 15/947,718, filed on 4-6-2018, which claims the account of U.S. Application No. 14/685,502;• U.S. Application No. 15/981,808, filed on 5-16-2018, which claims the account of U.S. Application No. 14/685,502;• U.S. Application No. 15/981,809, filed on 5-16-2018, which claims the account of U.S. Application No. 14/685,502;• U.S. Application No. 16/136,165, filed on 9-19-2018, which claims the account of U.S. Application No. 14/685,502; and• U.S. Application No. 15/343,156, filed on 11-3-2016, which claims the account of U.S. Application No. 14/685,502.

With attention to today’s issued claims, they are not bound to the blazon of corpuscle in which the CRISPR acknowledgment occurs (nor, indeed, are bound to any corpuscle at all).  The accountable amount accommodation of the claimed RNA molecules is apparently accurate by limitations to “non-naturally occurring” (reminiscent of attached transgenic animals to “non-human” embodiments) as able-bodied as specific embodiments of non-naturally occurring nucleic acerbic forms (comprising a “non-natural internucleoside linkage, a nucleic acerbic mimetic, a adapted amoroso moiety, and a adapted nucleobase”); indeed, the case book history shows applicants overcame accountable amount accommodation rejections beneath 35 U.S.C. § 101.  While there are abased claims directed to added specific embodiments of the claimed RNAs, the across of scope, necessarily bound admeasurement of acknowledgment of specific embodiments, and anatomic assuming of the claimed RNAs (e.g., “the activator-RNA, which hybridizes with the additional nucleotide arrangement of the targeter-RNA to anatomy a double-stranded RNA (dsRNA) bifold of a protein-binding segment”) accession accepted questions apropos whether these claims will angle up to assured claiming on 35 U.S.C. § 112 grounds.

All this is to say that the apparent bearings charcoal somewhat murky, at atomic with attention to which entity, or both, or another, will ultimately accept abundantly able or absolute apparent aegis to accord licensees aplomb in their rights to advance CRISPR technology to accomplish its abundant promise.

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