PATENT CLAIM ANALYSIS

Application Number: 15744531
Application Type: Utility
Filing Date: 2018-01
Publication Date: 2019-01
Patent Classification: ["514", "021200"]

Abstract:
The present disclosure provides human tear lipocalin muteins that specifically bind to LAG-3, which can be used in pharmaceutical applications, for example, as anti-cancer agents and/or immune modulators for the treatment or prevention of human diseases such as cancer, infectious diseases, and autoimmune diseases. The present disclosure further shows the human lipocalin muteins can inhibit the binding of LAG-3 to MHC class II on cells overexpressing MHC class II. The present disclosure also concerns methods of making LAG-3 binding lipocalin muteins described herein as well as compositions comprising such lipocalin muteins. The present disclosure further relates to nucleic acid molecules encoding such lipocalin muteins and to methods for generation of such lipocalin muteins and nucleic acid molecules. In addition, the application discloses therapeutic and/or diagnostic uses of these lipocalin muteins as well as compositions comprising one or more of such lipocalin muteins.

Claim (Index 15):
The lipocalin mutein of  claim 1 , wherein the mutein comprises one of the following sets of mutated amino acid residues in comparison with the linear polypeptide sequence of mature human tear lipocalin (SEQ ID NO: 1): (a) Arg\u200326\u2003\u2192 Ser;\u2003Glu\u200327\u2003\u2192 Asp;\u2003Phe\u200328\u2003\u2192 Cys;   Pro\u200329\u2003\u2192 Phe;\u2003Glu\u200330\u2003\u2192 Trp;\u2003Met\u200331\u2003\u2192 Ile;   Asn\u200332\u2003\u2192 Glu;\u2003Leu\u200333\u2003\u2192 Glu;\u2003Glu\u200334\u2003\u2192 Trp;   Leu\u200356\u2003\u2192 Asp;\u2003Ser\u200358\u2003\u2192 Phe;\u2003Arg\u200360\u2003\u2192 Phe;   Cys\u200361\u2003\u2192 Trp;\u2003Cys\u2003101\u2003\u2192 Ser;\u2003Leu\u2003105\u2003\u2192 Cys;   His\u2003106\u2003\u2192 Ala;\u2003Lys\u2003108\u2003\u2192 Phe;\u2003Arg\u2003111\u2003\u2192 Pro;   Lys\u2003114\u2003\u2192 Trp; and   Cys\u2003153\u2003\u2192 Ser;   (b) Ser\u200314\u2003\u2192 Pro;\u2003Asp\u200325\u2003\u2192 Ser;\u2003Arg\u200326\u2003\u2192 Gly;   Phe\u200328\u2003\u2192 Asp;\u2003Asn\u200332\u2003\u2192 Thr;\u2003Lys\u200352\u2003\u2192 Asn;   Met\u200355\u2003\u2192 Ala;\u2003Ser\u200358\u2003\u2192 Asp;\u2003Ala\u200366\u2003\u2192 Asn;   Ala\u200379\u2003\u2192 Glu;\u2003Ala\u200386\u2003\u2192 Asp;\u2003Cys\u2003101\u2003\u2192 Phe;   Leu\u2003105\u2003\u2192 Gly;\u2003Lys\u2003108\u2003\u2192 Thr;\u2003Val\u2003110\u2003\u2192 Ala;\u2003   Gly\u2003112\u2003\u2192 Thr;\u2003Lys\u2003114\u2003\u2192 Ala; and   Lys\u2003121\u2003\u2192 Thr;   (c) Arg\u200326\u2003\u2192 Phe;\u2003Glu\u200327\u2003\u2192 Val;\u2003Phe\u200328\u2003\u2192 Cys;   Pro\u200329\u2003\u2192 Leu;\u2003Glu\u200330\u2003\u2192 Tyr;\u2003Met\u200331\u2003\u2192 Asp;   Asn\u200332\u2003\u2192 Val;\u2003Leu\u200333\u2003\u2192 Pro;\u2003Leu\u200356\u2003\u2192 Gln;   Ser\u200358\u2003\u2192 Trp;\u2003Arg\u200360\u2003\u2192 Glu;\u2003Cys\u200361\u2003\u2192 Leu;   Cys\u2003101\u2003\u2192 Ser;\u2003Glu\u2003104\u2003\u2192 Tyr;\u2003Leu\u2003105\u2003\u2192 Cys;   His\u2003106\u2003\u2192 Val;\u2003Lys\u2003108\u2003\u2192 Tyr;\u2003Arg\u2003111\u2003\u2192 Pro;   Lys\u2003114\u2003\u2192 Trp; and   Cys\u2003153\u2003\u2192 Ser;   (d) Arg\u200326\u2003\u2192 Glu;\u2003Glu\u200327\u2003\u2192 Thr;\u2003Phe\u200328\u2003\u2192 Cys;   Pro\u200329\u2003\u2192 Trp;\u2003Glu\u200330\u2003\u2192 Trp;\u2003Met\u200331\u2003\u2192 Tyr;   Asn\u200332\u2003\u2192 Val;\u2003Leu\u200333\u2003\u2192 Asp;\u2003Glu\u200334\u2003\u2192 His;   Leu\u200356\u2003\u2192 Asn;\u2003Ile\u200357\u2003\u2192 Leu;\u2003Ser\u200358\u2003\u2192 Trp;   Arg\u200360\u2003\u2192 Phe;\u2003Cys\u200361\u2003\u2192 Trp;\u2003Cys\u2003101\u2003\u2192 Ser;   Leu\u2003105\u2003\u2192 Cys;\u2003His\u2003106\u2003\u2192 Gln;\u2003Lys\u2003108\u2003\u2192 Trp;   Arg\u2003111\u2003\u2192 Pro;\u2003Lys\u2003114\u2003\u2192 Trp; and   Cys\u2003153\u2003\u2192 Ser;   (e) Arg\u200326\u2003\u2192 Ser;\u2003Glu\u200327\u2003\u2192 Asp;\u2003Phe\u200328\u2003\u2192 Cys;   Pro\u200329\u2003\u2192 Phe;\u2003Glu\u200330\u2003\u2192 Trp;\u2003Met\u200331\u2003\u2192 Ile;   Asn\u200332\u2003\u2192 Asp;\u2003Leu\u200333\u2003\u2192 Asp;\u2003Glu\u200334\u2003\u2192 Val;   Leu\u200356\u2003\u2192 Asp;\u2003Ser\u200358\u2003\u2192 Phe;\u2003Arg\u200360\u2003\u2192 Phe;   Cys\u200361\u2003\u2192 Trp;\u2003Cys\u2003101\u2003\u2192 Ser;\u2003Leu\u2003105\u2003\u2192 Cys;   His\u2003106\u2003\u2192 Ala;\u2003Lys\u2003108\u2003\u2192 Tyr;\u2003Arg\u2003111\u2003\u2192 Pro;   Lys\u2003114\u2003\u2192 Trp; and   Cys\u2003153\u2003\u2192 Ser;   (f) Arg\u200326\u2003\u2192 Ser;\u2003Glu\u200327\u2003\u2192 Asp;\u2003Phe\u200328\u2003\u2192 Cys;   Pro\u200329\u2003\u2192 Phe;\u2003Glu\u200330\u2003\u2192 Trp;\u2003Met\u200331\u2003\u2192 Ile;   Asn\u200332\u2003\u2192 Asp;\u2003Leu\u200333\u2003\u2192 Glu;\u2003Glu\u200334\u2003\u2192 Val;\u2003   Leu\u200356\u2003\u2192 Asp;\u2003Ser\u200358\u2003\u2192 Phe;\u2003Arg\u200360\u2003\u2192 Phe;   Cys\u200361\u2003\u2192 Trp;\u2003Cys\u2003101\u2003\u2192 Ser;\u2003Leu\u2003105\u2003\u2192 Cys;   His\u2003106\u2003\u2192 Ala;\u2003Lys\u2003108\u2003\u2192 Tyr;\u2003Arg\u2003111\u2003\u2192 Pro;   Lys\u2003114\u2003\u2192 Trp; and   Cys\u2003153\u2003\u2192 Ser;   (g) Arg\u200326\u2003\u2192 Ser;\u2003Glu\u200327\u2003\u2192 Asp;\u2003Phe\u200328\u2003\u2192 Cys;\u2003   Pro\u200329\u2003\u2192 Phe;\u2003Glu\u200330\u2003\u2192 Trp;\u2003Met\u200331\u2003\u2192 Ile;   Asn\u200332\u2003\u2192 Glu;\u2003Leu\u200333\u2003\u2192 Glu;\u2003Glu\u200334\u2003\u2192 Trp;   Val\u200336\u2003\u2192 Ala;\u2003Asn\u200348\u2003\u2192 Asp;\u2003Leu\u200356\u2003\u2192 Asp;   Ser\u200358\u2003\u2192 Phe;\u2003Arg\u200360\u2003\u2192 Phe;\u2003Cys\u200361\u2003\u2192 Trp;   Val\u200385\u2003\u2192 Ala;\u2003Cys\u2003101\u2003\u2192 Ser;\u2003Leu\u2003105\u2003\u2192 Cys;   His\u2003106\u2003\u2192 Ala;\u2003Lys\u2003108\u2003\u2192 Phe;\u2003Arg\u2003111\u2003\u2192 Pro;   Lys\u2003114\u2003\u2192 Trp;\u2003Ser\u2003140\u2003\u2192 Gly; and   Cys\u2003153\u2003\u2192 Ser;   (h) Arg\u200326\u2003\u2192 Ser;\u2003Glu\u200327\u2003\u2192 Asp;\u2003Phe\u200328\u2003\u2192 Cys;\u2003   Pro\u200329\u2003\u2192 Phe;\u2003Glu\u200330\u2003\u2192 Trp;\u2003Met\u200331\u2003\u2192 Ile;   Asn\u200332\u2003\u2192 Asp;\u2003Leu\u200333\u2003\u2192 Glu;\u2003Glu\u200334\u2003\u2192 Val;   Leu\u200356\u2003\u2192 Asp;\u2003Ser\u200358\u2003\u2192 Phe;\u2003Arg\u200360\u2003\u2192 Phe;   Cys\u200361\u2003\u2192 Trp;\u2003Cys\u2003101\u2003\u2192 Ser;\u2003Leu\u2003105\u2003\u2192 Cys;   His\u2003106\u2003\u2192 Glu;\u2003Lys\u2003108\u2003\u2192 Phe;\u2003Arg\u2003111\u2003\u2192 Pro;   Lys\u2003114\u2003\u2192 Trp; and   Cys\u2003153\u2003\u2192 Ser;   (i) Arg\u200326\u2003\u2192 Ser;\u2003Glu\u200327\u2003\u2192 Asp;\u2003Phe\u200328\u2003\u2192 Cys;   Pro\u200329\u2003\u2192 Phe;\u2003Glu\u200330\u2003\u2192 Trp;\u2003Met\u200331\u2003\u2192 Ile;   Asn\u200332\u2003\u2192 Glu;\u2003Leu\u200333\u2003\u2192 Glu;\u2003Glu\u200334\u2003\u2192 Trp;   Val\u200336\u2003\u2192 Ala;\u2003Lys\u200352\u2003\u2192 Glu;\u2003Val\u200353\u2003\u2192 Ala;   Leu\u200356\u2003\u2192 Asp;\u2003Ser\u200358\u2003\u2192 Phe;\u2003Arg\u200360\u2003\u2192 Phe;   Cys\u200361\u2003\u2192 Trp;\u2003Cys\u2003101\u2003\u2192 Ser;\u2003Leu\u2003105\u2003\u2192 Cys;   His\u2003106\u2003\u2192 Ala;\u2003Lys\u2003108\u2003\u2192 Phe;\u2003Arg\u2003111\u2003\u2192 Pro;   Lys\u2003114\u2003\u2192 Trp; and   Cys\u2003153\u2003\u2192 Ser;   (j) Arg\u200326\u2003\u2192 Ser;\u2003Glu\u200327\u2003\u2192 Asp;\u2003Phe\u200328\u2003\u2192 Cys;   Pro\u200329\u2003\u2192 Phe;\u2003Glu\u200330\u2003\u2192 Trp;\u2003Met\u200331\u2003\u2192 Val;   Asn\u200332\u2003\u2192 Asp;\u2003Leu\u200333\u2003\u2192 Glu;\u2003Glu\u200334\u2003\u2192 Val;   Leu\u200356\u2003\u2192 Asp;\u2003Ser\u200358\u2003\u2192 Phe;\u2003Arg\u200360\u2003\u2192 Phe;   Cys\u200361\u2003\u2192 Trp;\u2003Cys\u2003101\u2003\u2192 Ser;\u2003Leu\u2003105\u2003\u2192 Cys;   His\u2003106\u2003\u2192 Ala;\u2003Lys\u2003108\u2003\u2192 Phe;\u2003Arg\u2003111\u2003\u2192 Pro;   Lys\u2003114\u2003\u2192 Trp; and   Cys\u2003153\u2003\u2192 Ser;   (k) Ser\u200314\u2003\u2192 Pro;\u2003Asp\u200325\u2003\u2192 Ser;\u2003Arg\u200326\u2003\u2192 Gly;   Phe\u200328\u2003\u2192 Asp;\u2003Met\u200331\u2003\u2192 Leu;\u2003Asn\u200332\u2003\u2192 Trp;   Lys\u200352\u2003\u2192 Ser;\u2003Met\u200355\u2003\u2192 Ala;\u2003Ser\u200358\u2003\u2192 Asp;   Ala\u200366\u2003\u2192 Asn;\u2003Ala\u200379\u2003\u2192 Glu;\u2003Ala\u200386\u2003\u2192 Asp;   Cys\u2003101\u2003\u2192 Phe;\u2003Leu\u2003105\u2003\u2192 Gly;\u2003His\u2003106\u2003\u2192 Tyr;   Lys\u2003108\u2003\u2192 Thr;\u2003Val\u2003110\u2003\u2192 Gly;\u2003Gly\u2003112\u2003\u2192 Met;   Lys\u2003114\u2003\u2192 Ala; and   Lys\u2003121\u2003\u2192 Thr;   (l) Ser\u200314\u2003\u2192 Pro;\u2003Asp\u200325\u2003\u2192 Ser;\u2003Arg\u200326\u2003\u2192 Ala;   Phe\u200328\u2003\u2192 Asp;\u2003Met\u200331\u2003\u2192 Leu;\u2003Asn\u200332\u2003\u2192 Val;   Lys\u200352\u2003\u2192 Ser;\u2003Met\u200355\u2003\u2192 Ala;\u2003Ser\u200358\u2003\u2192 Asp;   Ala\u200366\u2003\u2192 Asn;\u2003Ala\u200379\u2003\u2192 Glu;\u2003Ala\u200386\u2003\u2192 Asp;   Cys\u2003101\u2003\u2192 Phe;\u2003Leu\u2003105\u2003\u2192 Gly;\u2003Lys\u2003108\u2003\u2192 Thr;   Val\u2003110\u2003\u2192 Ala;\u2003Gly\u2003112\u2003\u2192 Thr;\u2003Lys\u2003114\u2003\u2192 Ala; and   Lys\u2003121\u2003\u2192 Thr;   (m) Ser\u200314\u2003\u2192 Pro;\u2003Asp\u200325\u2003\u2192 Ser;\u2003Arg\u200326\u2003\u2192 Asp;   Phe\u200328\u2003\u2192 Asp;\u2003Asn\u200332\u2003\u2192 Thr;\u2003Lys\u200352\u2003\u2192 Ser;   Met\u200355\u2003\u2192 Ala;\u2003Ser\u200358\u2003\u2192 Asp;\u2003Ala\u200366\u2003\u2192 Asn;   Ala\u200379\u2003\u2192 Glu;\u2003Ala\u200386\u2003\u2192 Asp;\u2003Cys\u2003101\u2003\u2192 Phe;   Leu\u2003105\u2003\u2192 Gly;\u2003His\u2003106\u2003\u2192 Gln;\u2003Lys\u2003108\u2003\u2192 Thr;   Val\u2003110\u2003\u2192 Gly;\u2003Gly\u2003112\u2003\u2192 Met;\u2003Lys\u2003114\u2003\u2192 Ala; and   Lys\u2003121\u2003\u2192 Thr;   (n) Ser\u200314\u2003\u2192 Pro;\u2003Asp\u200325\u2003\u2192 Ser;\u2003Arg\u200326\u2003\u2192 Glu;   Phe\u200328\u2003\u2192 Asp;\u2003Asn\u200332\u2003\u2192 Thr;\u2003Lys\u200352\u2003\u2192 Ser;   Met\u200355\u2003\u2192 Ala;\u2003Ser\u200358\u2003\u2192 Asp;\u2003Ala\u200366\u2003\u2192 Asn;   Ala\u200379\u2003\u2192 Glu;\u2003Ala\u200386\u2003\u2192 Asp;\u2003Cys\u2003101\u2003\u2192 Phe;   Leu\u2003105\u2003\u2192 Gly;\u2003Lys\u2003108\u2003\u2192 Thr;\u2003Val\u2003110\u2003\u2192 Gly;\u2003   Gly\u2003112\u2003\u2192 Met;\u2003Lys\u2003114\u2003\u2192 Ala; and   Lys\u2003121\u2003\u2192 Thr;   (o) Ser\u200314\u2003\u2192 Pro;\u2003Asp\u200325\u2003\u2192 Ser;\u2003Arg\u200326\u2003\u2192 Gly;   Phe\u200328\u2003\u2192 Asp;\u2003Asn\u200332\u2003\u2192 Met;\u2003Lys\u200352\u2003\u2192 Arg;   Met\u200355\u2003\u2192 Val;\u2003Ser\u200358\u2003\u2192 Asp;\u2003Ala\u200366\u2003\u2192 Asn;   Ala\u200379\u2003\u2192 Glu;\u2003Ala\u200386\u2003\u2192 Asp;\u2003Cys\u2003101\u2003\u2192 Phe;   Leu\u2003105\u2003\u2192 Gly;\u2003His\u2003106\u2003\u2192 Gln;\u2003Lys\u2003108\u2003\u2192 Thr;   Val\u2003110\u2003\u2192 Gly;\u2003Gly\u2003112\u2003\u2192 Met;\u2003Lys\u2003114\u2003\u2192 Ala; and   Lys\u2003121\u2003\u2192 Thr; or   (p) Arg\u200326\u2003\u2192 Phe;\u2003Glu\u200327\u2003\u2192 Val;\u2003Phe\u200328\u2003\u2192 Cys;   Pro\u200329\u2003\u2192 Leu;\u2003Glu\u200330\u2003\u2192 Asn;\u2003Met\u200331\u2003\u2192 Asp;   Asn\u200332\u2003\u2192 Tyr;\u2003Leu\u200333\u2003\u2192 Pro;\u2003Leu\u200356\u2003\u2192 Gln;   Ser\u200358\u2003\u2192 Trp;\u2003Arg\u200360\u2003\u2192 Glu;\u2003Cys\u200361\u2003\u2192 Pro;   Cys\u2003101\u2003\u2192 Ser;\u2003Glu\u2003104\u2003\u2192 Tyr;\u2003Leu\u2003105\u2003\u2192 Cys;   His\u2003106\u2003\u2192 Thr;\u2003Lys\u2003108\u2003\u2192 Tyr;\u2003Arg\u2003111\u2003\u2192 Pro;   Lys\u2003114\u2003\u2192 Trp; and   Cys\u2003153\u2003\u2192 Ser.

Metadata:
- Claim Count in Document: 2.0
- Percentile: 86.0
- Lexical Diversity: 2.01316
- Patent Class: 514.0
- Transitional Phrase Type: none
- Component Type: 0
- Foreign Priority: True
- Related Applications: ['15371698', '14402438', '14208629', '14839222', '12865237']

Analysis Scores:
- 35 USC 101 Eligibility (BERT): 0.8849758293534281
- 35 USC 102 Novelty (BERT): 0.6372841303611962
- Combined Prediction Score: 0.8602066594542049
- Mean Citation Score: 665.3214340000002
- Max Citation Score: 679.7365
- Similarity Product: 551.0640817452371

Labels:
- Claim Label 101: 1
- Claim Label 102: 1
- Claim Label 103: 1
- Claim Label 112: 1
- Combined Label: 1
- Label 101 Adjusted: 1

Dataset: test