By James DeGiulio —

On Apr. 6, 2010, Kylin Therapeutics of West
Lafayette, IN announced
the issuance of U.S. Patent No. 7,655,787,
which broadly covers a number of functionalities for Kylin's lead
technology platform, "pRNA," or "packaging RNA."  These functionalities include
receptor binding, ribozyme activity, and RNA-interference.  The main feature of pRNA is its ability
to enhance RNA stability in cells by altering RNA folding and protecting it
from exonuclease degradation.  The '787
patent, which issued on February 2, 2010, is based on principal inventor Peixuan
Guo's (below) original discovery of a virally-encoded 120-base RNA involved in
bacteriophage DNA packaging.

The '787 patent issued
from U.S. Application No. 10/373,612, filed February
24, 2003, and claims
the benefit of U.S. Provisional Application No. 60/433,697, filed
December 16, 2002.  The patent is also a continuation-in-part of International Application No. PCT/US01/26333,
filed August 23, 2001, which claims the benefit of U.S. Provisional Application No. 60/227,393, filed August 23, 2000.

The Examples provided in the patent specification
include construction of pRNA chimeras and in vitro pRNA-ribozyme activity
assays.  The '787 patent contains 18 total claims covering pRNA chimeras,
methods of making the pRNAs, and methods of delivery of DNA encoding the pRNAs.  The five independent claims recite:

1.  A pRNA chimera comprising:
    (a) a pRNA region; and
    (b) a spacer region comprising a biologically active RNA, the spacer region
covalently linked at its 5' and 3' ends to the pRNA region, wherein the biologically active RNA specifically
binds a pre-identified substrate; wherein the pRNA region comprises:
        (i) in the 5' to 3' direction beginning at the covalent linkage of the pRNA with the 3' end of the spacer
region a first loop; a second loop; and a lower stem-loop structure comprising
a bulge, a first stem section and a third loop;
        (ii) a second stem section interposed between the spacer region and the
stem-loop structure;
        (iii) a third stem section interposed between the stem-loop structure and the
first loop;
        (iv) a fourth stem section interposed between the first loop and the second
loop; and further comprises
        (v) an opening defining 5' and 3' ends of the pRNA chimera.

14.  A pRNA chimera comprising:
    (a) a pRNA
region; and
    (b) a spacer region comprising a biologically
active RNA that specifically binds a pre-identified ligand or receptor, the
spacer region covalently linked at its 5' and 3' ends to the pRNA region; wherein the pRNA region comprises:
        (i) in the 5' and 3' direction beginning at the covalent linkage of the pRNA with the 3' end of the spacer
region a first loop; a second loop; and a lower stem-loop structure comprising
a bulge, a first stem section and a third loop;
        (ii) a second stem section interposed between the spacer region and the
stem-loop structure;
        (iii) a third stem section interposed between the stem-loop structure and the
first loop;
        (iv) a fourth stem section interposed between the first loop and the second
loop; and further comprises
        (v) an opening defining 5' and 3' ends of the pRNA chimera.

15. A pRNA
chimera comprising:
    (a) a pRNA
region; and
    (b) a spacer region comprising a biologically
active RNA that comprises at least one of a specific binding activity and an
enzymatic activity, the spacer region covalently linked at its 5' and 3' ends
to the pRNA region;
wherein the pRNA region
comprises:
        (i) in the 5' and 3' direction beginning at the covalent linkage of the pRNA with the 3' end of the spacer
region a first loop; a second loop; and a lower stem-loop structure comprising
a bulge, a first stem section and a third loop;
        (ii) a second stem section interposed between the spacer region and the
stem-loop structure;
        (iii) a third stem section interposed between the stem-loop structure and the
first loop;
        (iv) a fourth stem section interposed between the first loop and the second loop;
and further comprises
        (v) an opening defining 5' and 3' ends of the pRNA chimera.

17. A pRNA
chimera comprising:
    (a) a pRNA
region; and
    (b) a spacer region comprising a biologically
active RNA that does not comprise the nucleotide sequence UAAUACGACUCACUAUA as
set forth in SEQ ID NO:8, the spacer region covalently linked at its 5' and 3'
ends to the pRNA region,
wherein the biologically active RNA specifically binds a pre-identified
substrate; wherein the pRNA
region comprises:
        (i) in the 5' to 3' direction beginning at the covalent linkage of the pRNA with the 3' end of the spacer
region a first loop; a second loop; and a lower stem-loop structure comprising
a bulge, a first stem section and a third loop;
        (ii) a second stem section interposed between the spacer region and the
stem-loop structure;
        (iii) a third stem section interposed between the stem-loop structure and the
first loop;
        (iv) a fourth stem section interposed between the first loop and the second
loop; and further comprises
        (v) an opening defining 5' and 3' ends of the pRNA chimera.

18.  A pRNA
chimera comprising:
    (a) a pRNA
region; and
    (b) a spacer region comprising a biologically
active RNA, the spacer region covalently linked at its 5' and 3' ends to the pRNA region, wherein the
biologically active RNA binds a pre-identified substrate and comprises a
polyribonucleotide selected from the group consisting of an RNA of at least
25-100, 46, 47, 63, 66, 94, 120, 168 and 188 nucleotides, wherein the pRNA region comprises:
        (i) in the 5' to 3' direction beginning at the covalent linkage of the pRNA with the 3' end of the spacer
region a first loop; a second loop; and a lower stem-loop structure comprising
a bulge, a first stem section and a third loop;
        (ii) a second stem section interposed between the spacer region and the
stem-loop structure;
        (iii) a third stem section interposed between the stem-loop structure and the
first loop;
        (iv) a fourth stem section interposed between the first loop and the second
loop; and further comprises
        (v) an opening defining 5' and 3' ends of the pRNA chimera.

James
DeGiulio has a doctorate in molecular biology and genetics from
Northwestern University and is a third-year law
student at the Northwestern University School of Law.  Dr. DeGiulio
was a member of MBHB's 2009 class of summer associates, and he can be
contacted at degiulio@mbhb.com.