★★★ ＜第29回知的財産翻訳検定試験【第14回英文和訳】＞ ★★★
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問１． 次の英文は欧州特許の従来技術（Background）の記載です。***(Start)***から***(End)***までの部分を日本語に訳して下さい。
Next-generation sequencing enables researchers to obtain large
amounts of data at a reduced cost and thus provides a tremendous
opportunity to genotype an individual of any species in depth (Lai et al.
"Genome-wide patterns of genetic variation among elite maize inbred lines"
2010, Nat Genet 42: 1027-1030). Recently, several genotyping-by-sequencing(GBS) approaches were developed to genotype hundreds of individuals
simultaneously (Andolfatto et al. "Multiplexed shotgun genotyping for rapid
and efficient genetic mapping" 2011, Genome Res 21: 610-17; Baird et al.
"Rapid SNP discovery and genetic mapping using sequenced RAD markers"
2008,

PLoS

One

3:e3376;

Elshireetal.

"ARobust,

SimpleGenotyping-by-Sequencing (GBS) Approach for High Diversity Species" 2011
PLoS One 6: e19379).
***(Start)***Conventional genotyping is most often conducted using pre-defined
SNP markers that must be discovered and validated in advance; thesemarkers are often population-specific. These SNPs are typically detected via
hybridization or by individual SNP-specific PCR-based assays. In contrast,
GBS technology enables the detection of a wider range of polymorphisms
than PCR-based assays (e.g., SNPs plus small insertions and/or deletions,e.g., "indels"). GBS technology eliminates the need to pre-discover andvalidate polymorphisms. Hence, GBS can be used in any polymorphic species
and any segregating population.
However, conventional GBS methods share at least two drawbacks.
First, conventional methods use double-stranded adaptors and, consequently,
associated methods require stringent control of the template:adaptor
concentration ratio in the adaptor ligation. As a result, precisely quantified,high quality input DNA is required as a starting material (see, e.g., Elshire
et al.). Second, these methods survey hundreds of thousands or more sites
and thus require numerous sequencing reads to generate enough coveragefor each site in each sample.
***(End)***For example, WO 2007/114693 discloses a method for identifying
molecular markers using double-stranded adaptors. The method includes
digesting nucleic acid with restriction enzymes and ligating each side with adouble-stranded adaptor to produce templates that are amplified andsequenced.

問２．***START***から***END***までを和訳してください。
***START***
The present invention is based, at least in part, on the discovery that
inhibiting or blocking Programmed Death 1 (PD-1) or Programmed Death- 1
Ligand (PD-L1) in combination with inhibition of an immune checkpoint
inhibitor (e.g., one or more of TEV1-3, LAG-3 or CTLA4) results in asynergistic therapeutic benefit for treating a hematologic cancer, e.g., amyeloma. This finding is unexpected given the lack of such benefit observedfor inhibiting or blocking other combinations of immune checkpoint
regulators.
Accordingly, in one aspect, the invention features a method oftreating a subject afflicted with a hematologic cancer comprisingadministering to the subject an inhibitor of PD-1 or PD-L1, and an inhibitorof an immune checkpoint regulator (e.g., an inhibitor of one or more ofTEVl-3, LAG-3 or CTLA4). In one embodiment, an inhibitor of PD-1 orPD-L1 is administered in combination with an inhibitor of TEVI-3. In
another embodiment, an inhibitor of PD-1 or PD-L1 is administered incombination with an inhibitor of LAG-3. In yet another embodiment, aninhibitor of PD-1 or PD-L1 is administered in combination with an inhibitorof CTLA-4.
***END***問３. ***(Start)***から***(End)***までの部分を日本語に訳して下さい。
Autophagy-Defective Tumor Cells Accumulate p62 in Response to Stress
To address the potential role of autophagy-dependant protein
quality control in tumor suppression, p62 modulation was assessed duringmetabolic stress and recovery in autophagy-competent (beclin1+/+ andatg5+/+) and autophagy-defective (beclin1+/- and atg5-/-) immortalized baby
mouse kidney (iBMK) cells.

***(Start)***Cells were engineered to express

Bcl-2, as the assessment of autophagy is facilitated in an apoptosis-defectivebackground. Under normal growth conditions, p62 levels were low inwild-type cells and slightly elevated in autophagy-defective iBMK cells ( FIG.
1B). Following 7 days of metabolic stress there was dramatic p62 induction
in wild-type cells that was further elevated in autophagy-defective cells in a
predominantly punctate pattern suggestive of p62 aggregation. In wild-typecells, most p62 aggregates were eliminated within 24 hr of recovery, whereas
p62 remained predominantly in large aggregates in autophagy-defectivecells ( FIG. 1B). p62 aggregates persisted in mutant cells after 2 days ofrecovery ( FIG. 1B) and remained so for at least a week (data not shown),
indicating that autophagy is required to limit the formation and to promote
the clearance of p62. Consistent with this, higher p62 levels were observed inautophagy-deficient (atg5-/-), as compared to wild-type (atg5+/+) iBMK cells
stably expressing myc-tagged p62 (myc-p62) (FIG. 1C). Thus, metabolic
stress induced p62 accumulation and aggregate formation, requiring
autophagy for elimination. ***(End)***問４. reference は明細書の一部を抜粋したものです。この内容を参考にして、以下の請求項を訳してください。
1. A small inhibitory nucleic acid (siRNA) molecule comprising between
about 15 base-pairs and about 40 base-pairs and at least one
universal-binding nucleotide.
2. The siRNA molecule of claim 1 wherein said universal-binding nucleotide
is selected from the group consisting of inosine,1-β-D-ribofuranosyl-5-nitroindole, and 1-β-D-ribofuranosyl-3-nitropyrrole.
4. The siRNA molecule of claim 3 wherein said siRNA molecule comprises a
double-stranded region.
14. The siRNA molecule of any one of claims 1- 13 wherein said
universal-binding nucleotide increases the binding specificity of said siRNAfor a target gene when the siRNA is contacted with a biological sample.
15. The siRNA molecule of any one of claims 1- 13 wherein said
universal-binding nucleotide reduces off-target effects of the siRNA molecule
when the siRNA is contacted with a biological cell.
16. The siRNA molecule of claim 1 wherein said siRNA is capable ofspecifically binding to a variant of a target gene expressed in a virus selectedfrom the group consisting of a retrovirus and a respiratory virus.

(reference)
The term “universal-binding nucleotide” as used herein refers to a nucleotide
analog that is capable of forming base-pairs with each of the natural
DNA/RNA nucleotides with little discrimination between them. Non-limiting
examples of universal-binding nucleotides include inosine,
1-β-D-ribofuranosyl-5-nitroindole, and/or 1-β-D-ribofuranosyl-3-nitropyrrole.