Anti-pcsk9 antibodies and use thereof

Abstract

The present invention is directed to antibodies and fragments thereof having binding specificity for PCSK9. Another embodiment of this invention relates to the antibodies described herein, and binding fragments thereof, comprising the sequences of the V H , V L and CDR polypeptides described herein, and the polynucleotides encoding them. The invention also contemplates conjugates of anti-PCSK9 antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. The invention also contemplates methods of making said anti-PCSK9 antibodies and binding fragments thereof. Embodiments of the invention also pertain to the use of anti-PCSK9 antibodies, and binding fragments thereof, for the diagnosis, assessment and treatment of diseases and disorders associated with PCSK9.

What is claimed is: 
     
         1 - 405 . (canceled) 
     
     
         406 . An anti-human PCSK9 antibody or antibody fragment selected from the following:
 i. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy chain comprises the CDR1 sequence of SEQ ID NO: 44, the CDR2 sequence of SEQ ID NO: 46, and the CDR3 sequence of SEQ ID NO: 48; and the variable light chain comprises the CDR1 sequence of SEQ ID NO: 64, the CDR2 sequence of SEQ ID NO: 66, and the CDR3 sequence of SEQ ID NO: 68;   ii. an anti-human PCSK9 antibody or antibody fragment that contains the variable heavy chain comprises the CDR1 sequence of SEQ ID NO: 84, the CDR2 sequence of SEQ ID NO: 86, and the CDR3 sequence of SEQ ID NO: 88; and the variable light chain comprises the CDR1 sequence of SEQ ID NO: 104, the CDR2 sequence of SEQ ID NO: 106, and the CDR3 sequence of SEQ ID NO: 108;   iii. an anti-human PCSK9 antibody or antibody fragment that contains the variable heavy chain comprises the CDR1 sequence of SEQ ID NO:124, the CDR2 sequence of SEQ ID NO: 126, and the CDR3 sequence of SEQ ID NO: 128; and the variable light chain comprises the CDR1 sequence of SEQ ID NO: 144, the CDR2 sequence of SEQ ID NO: 146, and the CDR3 sequence of SEQ ID NO: 148;   iv. an anti-human PCSK9 antibody or antibody fragment that contains the variable heavy chain comprises the CDR1 sequence of SEQ ID NO: 164, the CDR2 sequence of SEQ ID NO: 166, and the CDR3 sequence of SEQ ID NO: 168; and the variable light chain comprises the CDR1 sequence of SEQ ID NO: 184, the CDR2 sequence of SEQ ID NO: 186, and the CDR3 sequence of SEQ ID NO: 188;   v. an anti-human PCSK9 antibody or antibody fragment that contains the variable heavy chain comprises the CDR1 sequence of SEQ ID NO: 204, the CDR2 sequence of SEQ ID NO: 206, and the CDR3 sequence of SEQ ID NO: 208; and the variable light chain comprises the CDR1 sequence of SEQ ID NO: 224, the CDR2 sequence of SEQ ID NO: 226, and the CDR3 sequence of SEQ ID NO: 228;   vi. an anti-human PCSK9 antibody or antibody fragment that contains a variable heavy chain comprising the CDR1 sequence of SEQ ID NO: 244, the CDR2 sequence of SEQ ID NO: 246, and the CDR3 sequence of SEQ ID NO: 248; and the variable light chain comprises the CDR1 sequence of SEQ ID NO: 264, the CDR2 sequence of SEQ ID NO: 266, and the CDR3 sequence of SEQ ID NO: 268;   vii. an anti-human PCSK9 antibody or antibody fragment that contains a variable heavy chain which comprises the CDR1 sequence of SEQ ID NO: 284, the CDR2 sequence of SEQ ID NO: 286, and the CDR3 sequence of SEQ ID NO: 288; and the variable light chain comprises the CDR1 sequence of SEQ ID NO: 304, the CDR2 sequence of SEQ ID NO: 306, and the CDR3 sequence of SEQ ID NO: 308;   viii. an anti-human PCSK9 antibody or antibody fragment which contains a variable heavy chain comprises the CDR1 sequence of SEQ ID NO:324, the CDR2 sequence of SEQ ID NO: 326, and the CDR3 sequence of SEQ ID NO: 328; and the variable light chain comprises the CDR1 sequence of SEQ ID NO: 344, the CDR2 sequence of SEQ ID NO: 346, and the CDR3 sequence of SEQ ID NO: 348;   ix. an anti-human PCSK9 antibody or antibody fragment that contains a variable heavy chain comprising the CDR1 sequence of SEQ ID NO: 364, the CDR2 sequence of SEQ ID NO: 366, and the CDR3 sequence of SEQ ID NO: 368; and the variable light chain comprises the CDR1 sequence of SEQ ID NO: 384, the CDR2 sequence of SEQ ID NO: 386, and the CDR3 sequence of SEQ ID NO: 388;   x. an anti-human PCSK9 antibody or antibody fragment that contains a variable heavy chain comprising the CDR1 sequence of SEQ ID NO: 404, the CDR2 sequence of SEQ ID NO: 406, and the CDR3 sequence of SEQ ID NO: 408; and the variable light chain comprises the CDR1 sequence of SEQ ID NO: 424, the CDR2 sequence of SEQ ID NO: 426, and the CDR3 sequence of SEQ ID NO: 428;   xi. an anti-human PCSK9 antibody or antibody fragment that contains a variable heavy chain which comprises the CDR1 sequence of SEQ ID NO: 444, the CDR2 sequence of SEQ ID NO: 446, and the CDR3 sequence of SEQ ID NO: 448; and a variable light chain which comprises the CDR1 sequence of SEQ ID NO: 464, the CDR2 sequence of SEQ ID NO: 466, and the CDR3 sequence of SEQ ID NO: 468;   xii. an anti-human PCSK9 antibody or antibody fragment that contains a variable heavy chain which comprises the CDR1 sequence of SEQ ID NO: 484, the CDR2 sequence of SEQ ID NO: 486, and the CDR3 sequence of SEQ ID NO: 488; and the variable light chain comprises the CDR1 sequence of SEQ ID NO: 504, the CDR2 sequence of SEQ ID NO: 506, and the CDR3 sequence of SEQ ID NO: 508;   xiii. an anti-human PCSK9 antibody or antibody fragment that contains a e variable heavy chain which comprises the CDR1 sequence of SEQ ID NO:524, the CDR2 sequence of SEQ ID NO: 526, and the CDR3 sequence of SEQ ID NO: 528; and the variable light chain comprises the CDR1 sequence of SEQ ID NO: 544, the CDR2 sequence of SEQ ID NO: 546, and the CDR3 sequence of SEQ ID NO: 548;   xiv. an anti-human PCSK9 antibody or antibody fragment that contains a variable heavy chain which comprises the CDR1 sequence of SEQ ID NO: 564, the CDR2 sequence of SEQ ID NO: 566, and the CDR3 sequence of SEQ ID NO: 568; and the variable light chain comprises the CDR1 sequence of SEQ ID NO: 584, the CDR2 sequence of SEQ ID NO: 586, and the CDR3 sequence of SEQ ID NO: 588;   xv. an anti-human PCSK9 antibody or antibody fragment that contains a variable heavy chain which comprises the CDR1 sequence of SEQ ID NO: 604, the CDR2 sequence of SEQ ID NO: 606, and the CDR3 sequence of SEQ ID NO: 608; and a variable light chain which comprises the CDR1 sequence of SEQ ID NO: 624, the CDR2 sequence of SEQ ID NO: 626, and the CDR3 sequence of SEQ ID NO: 628;   xvi. an anti-human PCSK9 antibody or antibody fragment that contains a variable heavy chain which comprises the CDR1 sequence of SEQ ID NO: 644, the CDR2 sequence of SEQ ID NO: 646, and the CDR3 sequence of SEQ ID NO: 648; and a variable light chain which comprises the CDR1 sequence of SEQ ID NO: 664, the CDR2 sequence of SEQ ID NO: 666, and the CDR3 sequence of SEQ ID NO: 668;   xvii. an anti-human PCSK9 antibody or antibody fragment that contains a variable heavy chain which comprises the CDR1 sequence of SEQ ID NO: 684, the CDR2 sequence of SEQ ID NO: 686, and the CDR3 sequence of SEQ ID NO: 688; and a variable light chain which comprises the CDR1 sequence of SEQ ID NO: 704, the CDR2 sequence of SEQ ID NO: 706, and the CDR3 sequence of SEQ ID NO: 708;   xviii. an anti-human PCSK9 antibody or antibody fragment that contains a variable heavy chain which comprises the CDR1 sequence of SEQ ID NO:724, the CDR2 sequence of SEQ ID NO: 726, and the CDR3 sequence of SEQ ID NO: 728; and a variable light chain which comprises the CDR1 sequence of SEQ ID NO: 744, the CDR2 sequence of SEQ ID NO: 746, and the CDR3 sequence of SEQ ID NO: 748;   xix. an anti-human PCSK9 antibody or antibody fragment that contains a variable heavy chain which comprises the CDR1 sequence of SEQ ID NO: 764, the CDR2 sequence of SEQ ID NO: 766, and the CDR3 sequence of SEQ ID NO: 768; and a variable light chain which comprises the CDR1 sequence of SEQ ID NO: 784, the CDR2 sequence of SEQ ID NO: 786, and the CDR3 sequence of SEQ ID NO: 788;   xx. an anti-human PCSK9 antibody or antibody fragment that contains a variable heavy chain which comprises the CDR1 sequence of SEQ ID NO: 804, the CDR2 sequence of SEQ ID NO: 806, and the CDR3 sequence of SEQ ID NO: 808; and a variable light chain which comprises the CDR1 sequence of SEQ ID NO: 824, the CDR2 sequence of SEQ ID NO: 826, and the CDR3 sequence of SEQ ID NO: 828;   xxi. an anti-human PCSK9 antibody or antibody fragment that contains a variable heavy chain which comprises the CDR1 sequence of SEQ ID NO: 844, the CDR2 sequence of SEQ ID NO: 846, and the CDR3 sequence of SEQ ID NO: 848; and the variable light chain comprises the CDR1 sequence of SEQ ID NO: 864, the CDR2 sequence of SEQ ID NO: 866, and the CDR3 sequence of SEQ ID NO: 868;   xxii. an anti-human PCSK9 antibody or antibody fragment that contains a variable heavy chain which comprises the CDR1 sequence of SEQ ID NO: 884, the CDR2 sequence of SEQ ID NO: 886, and the CDR3 sequence of SEQ ID NO: 888; and a variable light chain which comprises the CDR1 sequence of SEQ ID NO: 904, the CDR2 sequence of SEQ ID NO: 906, and the CDR3 sequence of SEQ ID NO: 908;   xxiii. an anti-human PCSK9 antibody or antibody fragment that contains a variable heavy chain which comprises the CDR1 sequence of SEQ ID NO:924, the CDR2 sequence of SEQ ID NO: 926, and the CDR3 sequence of SEQ ID NO: 928; and a variable light chain which comprises the CDR1 sequence of SEQ ID NO: 944, the CDR2 sequence of SEQ ID NO: 946, and the CDR3 sequence of SEQ ID NO: 948;   xxiv. an anti-human PCSK9 antibody or antibody fragment that contains a variable heavy and light chains which comprise a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 2 and the variable light chain comprises SEQ ID NO: 22;   xxv. an anti-human PCSK9 antibody or antibody fragment that contains variable heavy and light chains which are each at least 90% identical to the variable heavy and light chains in SEQ ID NO: 2 and SEQ ID NO: 22;   xxvi. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 42 and the variable light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 62;   xxvii. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy and light chains are each at least 90% identical to the variable heavy and light chains in SEQ ID NO: 42 and SEQ ID NO: 62, respectively;   xxviii. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 82 and the variable light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 102;   xxix. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy and light chains are each at least 90% identical to the variable heavy and light chains in SEQ ID NO: 82 and SEQ ID NO: 102;   xxx. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 122 and the variable light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 142;   xxxi. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy and light chains are each at least 90% identical to the variable heavy and light chains in SEQ ID NO: 122 and SEQ ID NO: 142;   xxxii. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 162 and the variable light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 182;   xxxiii. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy and light chains are each at least 90% identical to the variable heavy and light chains in SEQ ID NO: 162 and SEQ ID NO: 182;   xxxiv. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 202 and the variable light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 222;   xxxv. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy and light chains are each at least 90% identical to the variable heavy and light chains in SEQ ID NO: 202 and SEQ ID NO: 222, respectively;   xxxvi. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 242 and the variable light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 262;   xxxvii. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy and light chains are each at least 90% identical to the variable heavy and light chains in SEQ ID NO: 242 and SEQ ID NO: 262, respectively;   xxxviii. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 282 and the variable light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 302;   xxxix. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy and light chains are each at least 90% identical to the variable heavy and light chains in SEQ ID NO: 282 and SEQ ID NO: 302, respectively;   xl. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 322 and the variable light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 342;   xli. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy and light chains are each at least 90% identical to the variable heavy and light chains in SEQ ID NO: 322 and SEQ ID NO: 342, respectively;   xlii. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 362 and the variable light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 382;   xliii. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy and light chains are each at least 90% identical to the variable heavy and light chains in SEQ ID NO: 362 and SEQ ID NO: 382, respectively;   xliv. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 402 and the variable light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 422;   xlv. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy and light chains are each at least 90% identical to the variable heavy and light chains in SEQ ID NO: 402 and SEQ ID NO: 422, respectively;   xlvi. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 442 and the variable light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 462;   xlvii. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy and light chains are each at least 90% identical to the variable heavy and light chains in SEQ ID NO: 442 and SEQ ID NO: 462, respectively;   xlviii. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 482 and the variable light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 502;   xlix. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy and light chains are each at least 90% identical to the variable heavy and light chains in SEQ ID NO: 482 and SEQ ID NO: 502, respectively;   I. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 522 and the variable light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 542;   Ii. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy and light chains are each at least 90% identical to the variable heavy and light chains in SEQ ID NO: 522 and SEQ ID NO: 542, respectively;   Ili. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 562 and the variable light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 582;   Iiii. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy and light chains are each at least 90% identical to the variable heavy and light chains in SEQ ID NO: 562 and SEQ ID NO: 582, respectively;   Iiv. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 602 and the variable light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 622;   Iv. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy and light chains are each at least 90% identical to the variable heavy and light chains in SEQ ID NO: 602 and SEQ ID NO: 622, respectively;   Ivi. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 642 and the variable light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 662;   Ivii. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy and light chains are each at least 90% identical to the variable heavy and light chains in SEQ ID NO: 642 and SEQ ID NO: 662, respectively;   Iviii. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 682 and the variable light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 702;   Iix. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy and light chains are each at least 90% identical to the variable heavy and light chains in SEQ ID NO: 682 and SEQ ID NO: 702, respectively;   Ix. an anti-human PCSK9 antibody or antibody fragment wherein The anti-human PCSK9 antibody or antibody fragment of any one of claims  1 - 10 , wherein the variable heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 722 and the variable light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 742;   Ixi. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy and light chains are each at least 90% identical to the variable heavy and light chains in SEQ ID NO: 722 and SEQ ID NO: 742, respectively;   Ixii. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 762 and the variable light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 782;   Ixiii. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy and light chains are each at least 90% identical to the variable heavy and light chains in SEQ ID NO: 762 and SEQ ID NO: 782, respectively;   Ixiv. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 802 and the variable light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 822;   Ixv. an anti-human PCSK9 antibody or antibody fragment wherein. the variable heavy and light chains are each at least 90% identical to the variable heavy and light chains in SEQ ID NO: 802 and SEQ ID NO: 822, respectively;   Ixvi. an anti-human PCSK9 antibody or antibody fragment wherein. the variable heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 842 and the variable light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 862;   Ixvii. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy and light chains are each at least 90% identical to the variable heavy and light chains in SEQ ID NO: 842 and SEQ ID NO: 862, respectively;   Ixviii. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 882 and the variable light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 902;   Ixix. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy and light chains are each at least 90% identical to the variable heavy and light chains in SEQ ID NO: 882 and SEQ ID NO: 902, respectively;   Ixx. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 922 and the variable light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 942;   Ixxi. an anti-human PCSK9 antibody or antibody fragment wherein the variable heavy and light chains are each at least 90% identical to the variable heavy and light chains in SEQ ID NO: 922 and SEQ ID NO: 942, respectively;   Ixxii. an anti-human PCSK9 antibody or antibody fragment wherein the heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 1 and the light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 21;   Ixxiii. an anti-human PCSK9 antibody or antibody fragment wherein the heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 41 and the light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 61;   Ixxiv. an anti-human PCSK9 antibody or antibody fragment wherein the heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 81 and the light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 101;   Ixxv. an anti-human PCSK9 antibody or antibody fragment wherein the heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 121 and the light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 141;   Ixxvi. an anti-human PCSK9 antibody or antibody fragment wherein the heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 161 and the light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 181;   Ixxvii. an anti-human PCSK9 antibody or antibody fragment wherein the heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 201 and the light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 221;   Ixxviii. an anti-human PCSK9 antibody or antibody fragment wherein the heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 241 and the light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 261;   Ixxix. an anti-human PCSK9 antibody or antibody fragment wherein the heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 281 and the light chain comprises SEQ ID NO: 301;   Ixxx. an anti-human PCSK9 antibody or antibody fragment wherein the heavy chain comprises SEQ ID NO: 321 and the light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 341;   Ixxxi. an anti-human PCSK9 antibody or antibody fragment wherein the heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 361 and the light chain comprises SEQ ID NO: 381;   Ixxxii. an anti-human PCSK9 antibody or antibody fragment wherein the heavy chain comprises SEQ ID NO: 401 and the light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 421;   Ixxxiii. an anti-human PCSK9 antibody or antibody fragment wherein the heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 441 and the light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 461;   Ixxxiv. an anti-human PCSK9 antibody or antibody fragment wherein the heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 481 and the light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 501;   Ixxxv. an anti-human PCSK9 antibody or antibody fragment wherein the heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 521 and the light chain comprises SEQ ID NO: 541;   Ixxxvi. an anti-human PCSK9 antibody or antibody fragment wherein the heavy chain comprises SEQ ID NO: 561 and the light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 581;   Ixxxvii. an anti-human PCSK9 antibody or antibody fragment wherein the heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 601 and the light chain comprises SEQ ID NO: 621;   Ixxxviii. an anti-human PCSK9 antibody or antibody fragment wherein the heavy chain comprises SEQ ID NO: 641 and the light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 661;   Ixxxix. an anti-human PCSK9 antibody or antibody fragment wherein the heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 681 and the light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 701;   xc. an anti-human PCSK9 antibody or antibody fragment wherein the heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 721 and the light chain comprises SEQ ID NO: 741;   xci. an anti-human PCSK9 antibody or antibody fragment wherein the heavy chain comprises SEQ ID NO: 761 and the light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 781;   xcii. an anti-human PCSK9 antibody or antibody fragment wherein the heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 801 and the light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 821;   xciii. an anti-human PCSK9 antibody or antibody fragment wherein the heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 841 and the light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 861;   xciv. an anti-human PCSK9 antibody or antibody fragment wherein the heavy chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 881 and the light chain comprises SEQ ID NO: 901;   xcv. an anti-human PCSK9 antibody or antibody fragment the heavy chain comprises SEQ ID NO: 921 and the light chain comprises a sequence at least 80, 85, 90, 95, 96, 97, 98, 99 or 100% identical to SEQ ID NO: 941;   xcvi. an anti-human PCSK9 antibody or antibody fragment according to any one of the foregoing wherein the antibody or antibody fragment is selected from the group consisting of chimeric, humanized, and human antibodies or antibody fragments;   xcvii. an anti-human PCSK9 antibody or antibody fragment according to any one of the foregoing wherein the antibody or antibody fragment is selected from the group consisting of scFvs, camelbodies, nanobodies, IgNAR, F.sub.ab fragments, F.sub.ab′ fragments, MetMab like antibodies, monovalent antibody fragments, and F(ab′)2 fragments;   xcviii. an anti-human PCSK9 antibody or antibody fragment according to any one of the foregoing, wherein the antibody or antibody fragment substantially or entirely lacks N-glycosylation and/or O-glycosylation;   xcix. an anti-human PCSK9 antibody or antibody fragment according to any one of the foregoing, wherein the antibody or antibody fragment comprises a human constant domain;   c. an anti-human PCSK9 antibody or antibody fragment according to any one of the foregoing, wherein the antibody is an IgG1, IgG2, IgG3, or IgG4 antibody;   ci. an anti-human PCSK9 antibody or antibody fragment according to any one of the foregoing, wherein the antibody or antibody fragment comprises an Fc region that has been modified to alter at least one of effector function, half-life, proteolysis, or glycosylation;   cii. an anti-human PCSK9 antibody or antibody fragment according to any one of the foregoing, wherein the Fc region contains one or more mutations that alters or eliminates N- and/or O-glycosylation;   ciii. an anti-human PCSK9 antibody or antibody fragment according to any one of the foregoing wherein the antibody or antibody fragment is a humanized antibody or antibody fragment;   civ. an anti-human PCSK9 antibody or antibody fragment according to any one of the foregoing, wherein the antibody or antibody fragment binds to PCSK9 with a dissociation constant (K D ) of less than or equal to 10 −2  M, 5×10 −3  M, 10 −3  M, 5×10 −4  M, 10 −4  M, 5×10 −5  M, 10 −5  M, 5×10 −6  M, 10 −6  M, 5×10 −7  M, 10 −7  M, 5×10 −8  M, 10 −8  M, 5×10 −9  M, 10 −9  M, 5×10 −10  M, 10 −10  M, 5×10 −11  M, 10 −11  M, 5×10 −12  M, 10 −12  M, 5×10 −13  M, or 10 −13  M;   cv. an anti-human PCSK9 antibody or antibody fragment according to any one of the foregoing, wherein the antibody or antibody fragment binds to PCSK9 with a-dissociation constant (K D ) of less than or equal to 10 −11  M, 5×10 −12  M, or 10 −12 M;   cvi. an anti-human PCSK9 antibody or antibody fragment according to any one of the foregoing, which binds to PCSK9 with an off-rate of less than or equal to 10 −4  S −1 , 5×10 −5  S 1 , 10 −5  S −1 , 5×10 −6  S −1 , 10 −6  5×10 −7  S −1  or 10 −7  S −1 ;   cvii. an anti-human PCSK9 antibody or antibody fragment according to any one of the foregoing, wherein the antibody or antibody fragment is directly or indirectly attached to a detectable label or therapeutic agent;   cviii. an anti-human PCSK9 antibody or antibody fragment according to any one of the foregoing, which when administered to a human subject inhibits or neutralizes at least one biological effect elicited by PCSK9;   cix. an anti-human PCSK9 antibody or antibody fragment according to any one of the foregoing, which when administered to a human subject reduces serum cholesterol;   cx. an anti-human PCSK9 antibody or antibody fragment according to any one of the foregoing, which is capable of inhibiting the binding of PCSK9 to LDLR;   cxi. an anti-human PCSK9 antibody or antibody fragment according to any one of the foregoing, wherein the antibody or antibody fragment binds to PCSK9 with a K D  that is less than about 100 nM;   cxii. an anti-human PCSK9 antibody or antibody fragment according to any one of the foregoing, wherein the antibody or antibody fragment binds to PCSK9 with a K D  that is less than about 10 nM;   cxiii. an anti-human PCSK9 antibody or antibody fragment according to any one of the foregoing, wherein the antibody or antibody fragment binds to PCSK9 with a KD that is less than about 1 nM;   cxiv. an anti-human PCSK9 antibody or antibody fragment according to any one of the foregoing, wherein the antibody or antibody fragment binds to PCSK9 with a K D  that is between about 1 and about 10 nM;   cxv. an anti-human PCSK9 antibody or antibody fragment according to any one of the foregoing, wherein the antibody or antibody fragment binds to PCSK9 with a K D  that is between about 0.1 and about 1 nM;   cxvi. an anti-human PCSK9 antibody or antibody fragment according to any one of the foregoing, wherein the antibody or antibody fragment binds to PCSK9 with a KD that is between 0.12 and 7.99 nM;   cxvii. an anti-human PCSK9 antibody or antibody fragment according to any one of the foregoing, wherein the antibody or antibody fragment is attached to at least one effector moiety;   cxviii. an anti-human PCSK9 antibody or antibody fragment according to any one of the foregoing, comprising an effector moiety which comprises a chemical linker;   cxix. an anti-human PCSK9 antibody or antibody fragment according to any one of the foregoing, wherein the antibody or antibody fragment is attached to one or more detectable moieties optionally a fluorescent dye, enzyme, substrate, bioluminescent material, radioactive material, chemiluminescent moiety, or mixtures thereof; or   cxx. an anti-human PCSK9 antibody or antibody fragment according to any one of the foregoing wherein the antibody or antibody fragment is attached to one or more functional moieties.   
     
     
         407 . An anti-idiotypic antibody produced against an anti-human PCSK9 antibody or antibody fragment according to any one of the antibodies or antibody fragments in  claim 406 . 
     
     
         408 . A composition suitable for therapeutic, prophylaxis, or a diagnostic use comprising a therapeutically, prophylactically or diagnostically effective amount of at least one antibody or antibody fragment according to  claim 406 . 
     
     
         409 . The composition of  claim 408  which comprises one or more of the following:
 i. is suitable for subcutaneous administration; 
 ii. is suitable for intravenous administration; 
 iii. is suitable for topical administration; 
 iv. is lyophilized; 
 v. it comprises a pharmaceutically acceptable diluent, carrier, solubilizer, emulsifier, preservative, or mixture thereof; 
 vi. it comprises another active agent optionally selected from statins, ACE inhibitors, Angiotensin II receptor blockers (ARBs), Antiarrhythmics, Antiplatelet Drugs, aspirin, beta blockers, amiodarone, digoxin, aspirin, anti-clotting agents, digoxin, diuretics, heart failure drugs, vasodilators, blood thinners, other anti-cholesterol drugs such as holestyramine (Questran), gemfibrozil (Lopid, Gemcor), Omacor, pantethine, anti-hypertensives, antidiabetigenic drugs, Meglitinides, Sulfonylurea, and Thiazolidinediones further wherein optionally the ACE inhibitor is selected from: Capoten (captopril), Vasotec (enalapril), Prinivil, Zestril (lisinopril), Lotensin (benazepril), Monopril (fosinopril), Altace (ramipril), Accupril (quinapril), Aceon (perindopril), Mavik (trandolapril), Univasc (moexipril); the ARB is selected from: Cozaar (losartan), Diovan (valsartan), Avapro (irbesartan), Atacand (candesartan), and Micardis (telmisartan); the Antiarrhythmic is selected from Tambocor (flecamide), Procanbid (procainamide), Cordarone (amiodarone), and Betapace (sotalol); the anticlotting agent is selected from Tissue plasminogen activator (TPA), Tenecteplase, Alteplase, Urokinase, Reteplase, Streptokinase, Fxl antagonist and anto-thrombotics; the Beta blocker is selected from Sectral (acebutolol), Zebeta (bisoprolol), Brevibloc (esmolol), Inderal (propranolol), Tenormin (atenolol), Normodyne, Trandate (labetalol), Coreg (carvedilol), Lopressor, and Toprol-XL (metoprolol); the calcium channel blocker is selected from: Norvasc (amlodipine), Plendil (felodipine), Cardizem, Cardizem CD, Cardizem SR, Dilacor XR, Diltia XT, Tiazac (diltiazem), Calan, Calan SR, Covera-HS, Isoptin, Isoptin SR, Verelan, Verelan PM (verapamil), Adalat, Adalat CC, Procardia, Procardia XL (nifedipine), Cardene, Cardene SR (nicardipine), Sular (nisoldipine), Vascor (bepridil), and Caduet which is a combination of a statin cholesterol drug and amlodipine; the diuretic is selected from: Lasix (furosemide), Bumex (bumetanide), Demadex (torsemide), Esidrix (hydrochlorothiazide), Zaroxolyn (metolazone), and Aldactone (spironolactone); the heart failure drug is selected from Dobutrex (dobutamine), and Primacor (milrinone); the vasodilator is selected from Dilatrate-SR, Iso-Bid, Isonate, Isorbid, Isordil, Isotrate, Sorbitrate (isosorbide dinitrate), IMDUR (isorbide mononitrate), and BiDil (hydralazine with isosorbide dinitrate; the blood thinner is selected Warfarin (coumadin), Heparin, Lovenox, and Fragmin; 
 vii. the composition further comprises another therapeutic agent that elevates the availability of LDLR protein; 
 viii. the composition further comprises another therapeutic agent that blocks or inhibits cholesterol synthesis; 
 ix. the composition further comprises a statin optionally atorvastatin, cerivastatin, fluvastatin, lovastatin, mevastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin, or mixtures thereof; 
 x. the composition further comprises another therapeutic agent that elevates the HDL level, or an agent which decreases triglyceride levels, or both; 
 xi. the composition further comprises a fibrate, optionally bezafibrate, ciprofibrate, clofibrate, gemfibrozil, fenofibrate, or mixtures thereof; 
 xii. the composition further comprises a bile sequestering agent, optionally cholestyramine, colesevelam, colestipol, or mixtures thereof; 
 xiii. the composition further comprises an agent that decreases cholesterol absorption in the intestines optionally ezetimibe; 
 xiv. the composition comprises an agent that that inhibits hepatic triglyceride production, inhibits VLDL secretions, or both optionally acipimox; 
 xv. the composition further comprises an agent that decreases lipid absorption in the intestines, optionally orlistat, lipstatin, or mixtures thereof; 
 xvi. the composition further comprises an agent that is an anti-hypertensive, an agent that treat angina, or both optionally said anti-hypertensive or anti-angina agent is selected from a diuretic, an adrenergic receptor antagonist, a calcium channel blocker, a renin inhibitor, an ACE inhibitor, an angiotensin II receptor antagonist, as aldosterone antagonist, a vasodilator or an alpha-2 agonist; optionally the diuretics include bumetanide, thacrynic acid, furosemide, and torsemide; a thiazide diuretic such as epitizide, hydrochlorothiazide or chlorothiazide, or bendroflumethiazide; a thiazide-like diuretic such as indapamide, chlorthalidone, or metolazone; a potassium-sparing diuretic such as amiloride, triamterene, or spironolactone; the adrenergic receptor antagonists include beta blockers such as atenolol, metoprolol, nadolol, oxprenolol, pindolol, propranolol, or timolol; the alpha blockers include doxazocin, phentolamine, indoramin, phenoxybenzamine, prazosin, terazosin, and tolazoline; mixed alpha+beta blockers such as bucindolol, carvedilol, and labetalol; the calcium channel blockers include dihydropyridines such as amlodipine, felodipine, isradipine, lercanidipine, nicardipine, nifedipine, nimodipine, and nitrendipine; non-dihydropyridines such as diltiazem and verapamil; renin inhibitors such as Aliskiren; ACE inhibitors such as captopril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril, trandolapril, and benazepril; angiotensin II receptor antagonists such as candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, and valsartan; aldosterone antagonists such as eplerenone andspironolactone; vasodilators such as sodium nitroprusside; and Alpha-2 agonists such as Clonidine, Guanabenz, Methyldopa, Moxonidine, Guanethidine or Reserpine; or a nitrate such as nitroglycerin (glyceryl trinitrate), pentaerythritol tetranitrate, isosorbide dinitrate or isosorbide mononitrate; 
 xvii. the composition further comprises at least one other agent, wherein the combination allows for mitigation of undesirable side effects of at least one other agent contained therein. (xviii) the composition comprises at least one therapeutic agent for inflammation optionally s a cyclooxygenase type 1 inhibitor, a cyclooxygenase type 2 inhibitor, a small molecule modulator of p38-MAPK, a small molecule modulator of intracellular molecules involved in inflammation pathways, or mixtures thereof; 
 xviii. the composition of any of the foregoing which is lyophilized, stabilized and/or formulated for administration by injection; or 
 xix. any combination of the foregoing. 
 
     
     
         410 . A method of therapy comprising administering an antibody or antibody fragment according to  claim 406 , or a composition containing according to  claim 409  for effecting at least one of the following in a subject in need thereof:
 i. blocking, inhibiting or neutralizing one or more biological effects associated with PCSK9; 
 ii. treating or preventing a condition associated with elevated serum cholesterol levels; 
 iii. treating or preventing elevated serum cholesterol levels in a patient in need thereof or at risk of developing elevated serum cholesterol levels because of an existing condition, optionally hypercholesterolemia, coronary heart disease, hyperlipidemia, hypertriglyceridaemia, sitosterolemia, atherosclerosis, arteriosclerosis metabolic syndrome, acute coronary syndrome, vascular inflammation, xanthoma, diabetes, obesity, hypertension, or angina; and/or 
 ii. treating or preventing a disorder involving cholesterol or lipid homeostasis or complications associated therewith; optionally wherein the treated condition is selected from hypercholesterolemia, hyperlipidemia, hypertriglyceridaemia, and sitosterolemia. 
 
     
     
         411 . The method of  claim 410  wherein the method further comprises
 i. administering separately or co-administering another agent, which agent that elevates the availability of LDLR protein or which blocks or inhibits cholesterol synthesis; 
 ii. the administration is part of a therapeutic regimen that further includes the administration of at least one of the following: statins, ACE inhibitors, Angiotensin II receptor blockers (ARBs), Antiarrhythmics, Antiplatelet Drugs, aspirin, beta blockers, amiodarone, digoxin, aspirin, anti-clotting agents, digoxin, diuretics, heart failure drugs, vasodilators, blood thinners, other anti-cholesterol drugs such as holestyramine (Questran), gemfibrozil (Lopid, Gemcor), Omacor, pantethine, anti-hypertensives, antidiabetigenic drugs, Meglitinides, Sulfonylurea, and Thiazolidinediones optionally wherein the ACE inhibitor is selected from: Capoten (captopril), Vasotec (enalapril), Prinivil, Zestril (lisinopril), Lotensin (benazepril), Monopril (fosinopril), Altace (ramipril), Accupril (quinapril), Aceon (perindopril), Mavik (trandolapril), Univasc (moexipril), the ARB is selected from: Cozaar (losartan), Diovan (valsartan), Avapro (irbesartan), Atacand (candesartan), and Micardis (telmisartan); the antiarythmic is selected from: Tambocor (flecamide), Procanbid (procainamide), Cordarone (amiodarone), and Betapace (sotalol); the anti-clotting agent is selected from: Tissue plasminogen activator (TPA), Tenecteplase, Alteplase, Urokinase, Reteplase, and Streptokinase; the Beta-blocker is selected from: Sectral (acebutolol), Zebeta (bisoprolol), Brevibloc (esmolol), Inderal (propranolol), Tenormin (atenolol), Normodyne, Trandate (labetalol), Coreg (carvedilol), Lopressor, and Toprol-XL (metoprolol); the calcium channel blocker is selected from: Norvasc (amlodipine), Plendil (felodipine), Cardizem, Cardizem CD, Cardizem SR, Dilacor XR, Diltia XT, Tiazac (diltiazem), Calan, Calan SR, Covera-HS, Isoptin, Isoptin SR, Verelan, Verelan PM (verapamil), Adalat, Adalat CC, Procardia, Procardia XL (nifedipine), Cardene, Cardene SR (nicardipine), Sular (nisoldipine), Vascor (bepridil), and Caduet which is a combination of a statin cholesterol drug and amlodipine; the antidiruetic is selected from: Lasix (furosemide), Bumex (bumetanide), Demadex (torsemide), Esidrix (hydrochlorothiazide), Zaroxolyn (metolazone), and Aldactone (spironolactone); the heart failure drug is selected from Dobutrex (dobutamine), and Primacor (milrinone); the vasodilator is selected from: Dilatrate-SR, Iso-Bid, Isonate, Isorbid, Isordil, Isotrate, Sorbitrate (isosorbide dinitrate), IMDUR (isorbide mononitrate), and BiDil (hydralazine with isosorbide dinitrate; the blood thinner is selected from Warfarin (coumadin), Heparin, Lovenox, and Fragmin; the agent that elevates the availability of LDLR protein or which blocks or inhibits cholesterol synthesis is administered simultaneously with the antibody or composition containing the another agent that elevates the availability of LDLR protein or which blocks or inhibits cholesterol synthesis is administered sequentially relative to the administration of the antibody or composition containing; the agent that blocks or inhibits cholesterol synthesis protein comprises a statin; the statin optionally is selected from atorvastatin, cerivastatin, fluvastatin, lovastatin, mevastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin, or mixtures thereof; 
 iii. the method further comprises administering an agent that elevates the HDL level, an agent that decreases triglyceride levels, or both optionally a fibrate such as bezafibrate, ciprofibrate, clofibrate, gemfibrozil, fenofibrate, or mixtures thereof iv. the method further comprises administering a bile sequestering agent, optionally cholestyramine, colesevelam, colestipol, or mixtures thereof; 
 v. the method further comprises administering an agent that decreases cholesterol absorption in the intestines optionally ezetimibe; 
 vi. the method further comprises administering an agent that inhibits hepatic triglyceride production, inhibits VLDL secretions, or both optionally acipimox; 
 vii. the method further comprises administering an agent that decreases lipid absorption in the intestines, optionally orlistat, lipstatin, or mixtures thereof; 
 viii. the method further comprises administering an agent that is an anti-hypertensive, one that treats angina, or both optionally wherein said anti-hypertensive or anti-angina agent is selected from a diuretic, an adrenergic receptor antagonist, a calcium channel blocker, a renin inhibitor, an ACE inhibitor, an angiotensin II receptor antagonist, as aldosterone antagonist, a vasodilator or an alpha-2 agonist the diuretics include bumetanide, thacrynic acid, furosemide, and torsemide; a thiazide diuretic such as epitizide, hydrochlorothiazide or chlorothiazide, or bendroflumethiazide; a thiazide-like diuretic such as indapamide, chlorthalidone, or metolazone; a potassium-sparing diuretic such as amiloride, triamterene, or spironolactone; the adrenergic receptor antagonists include beta blockers such as atenolol, metoprolol, nadolol, oxprenolol, pindolol, propranolol, or timolol; the alpha blockers include doxazocin, phentolamine, indoramin, phenoxybenzamine, prazosin, terazosin, and tolazoline; mixed alpha+beta blockers such as bucindolol, carvedilol, and labetalol; the calcium channel blockers include dihydropyridines such as amlodipine, felodipine, isradipine, lercanidipine, nicardipine, nifedipine, nimodipine, and nitrendipine; non-dihydropyridines such as diltiazem and verapamil; renin inhibitors such as Aliskiren; an ACE inhibitors such as captopril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril, trandolapril, and benazepril; angiotensin II receptor antagonists such as candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, and valsartan; aldosterone antagonists such as eplerenone andspironolactone; vasodilators such as sodium nitroprusside; and Alpha-2 agonists such as Clonidine, Guanabenz, Methyldopa, Moxonidine, Guanethidine or Reserpine; or a nitrate such as nitroglycerin (glyceryl trinitrate), pentaerythritol tetranitrate, isosorbide dinitrate or isosorbide mononitrate; 
 ix. the method further comprises administering at least one other agent, wherein the combination allows for mitigation of undesirable side effects of at least one other agent; 
 x. the antibody or antibody fragment or composition containing and at least one other agent are administered concurrently; 
 xi. the antibody or antibody fragment is administered before or after the at least one other active agent; (xiii) the method lowers serum cholesterol level in a subject; 
 xii. the method increases LDLR protein level in a subject; 
 xiii. the antibody or antibody fragment or composition containing are administered with an agent that inhibits inflammation optionally a cyclooxygenase type 1 inhibitor, a cyclooxygenase type 2 inhibitor, a small molecule modulator of p38-MAPK, a small molecule modulator of intracellular molecules involved in inflammation pathways, or mixtures thereof; 
 xiv. the method is used to treat or prevent a disease or the complications of a disease or condition selected from hypercholesterolemia, heart disease, metabolic syndrome, diabetes, coronary heart disease, stroke, cardiovascular diseases, Alzheimer's disease, dyslipidemias, elevated total serum cholesterol, elevated LDL, elevated triglycerides, elevated VLDL, low HDL, metabolic syndrome, diabetes mellitus, familial combined hyperlipidemia, familial hypertriglyceridemia, familial hypercholesterolemias, including heterozygous hypercholesterolemia, homozygous hypercholesterolemia, familial defective apoplipoprotein B-100; polygenic hypercholesterolemia; remnant removal disease, hepatic lipase deficiency; dyslipidemia secondary to any of the following: dietary indiscretion, hypothyroidism, drugs including estrogen and progestin therapy, beta-blockers, and thiazide diuretics; nephrotic syndrome, chronic renal failure, Cushing's syndrome, primary biliary cirrhosis, glycogen storage diseases, hepatoma, cholestasis, acromegaly, insulinoma, isolated growth hormone deficiency, and alcohol-induced hypertriglyceridemia. atherosclerotic diseases such as coronary heart disease, coronary artery disease, peripheral arterial disease, stroke (ischaemic and hemorrhagic), angina pectoris, cerebrovascular disease and acute coronary syndrome, myocardial infarction, reducing the risk of: nonfatal heart attacks, fatal and non-fatal strokes, certain types of heart surgery, hospitalization for heart failure, chest pain in patients with heart disease, and/or cardiovascular events because of established heart disease such as prior heart attack, prior heart surgery, and/or chest pain with evidence of clogged arteries, or the risk of recurrent cardiovascular events. 
 
     
     
         412 . An isolated nucleic acid or nucleic acids which encode for and when expressed in a suitable host cell result in the expression of an anti-human PCSK9 antibody or antibody fragment or the variable heavy or light chain thereof according to  claim 406 . 
     
     
         413 . A vector or vectors comprising the nucleic acid sequence or sequences of any of  claim 412 . 
     
     
         414 . A host cell comprising nucleic acid sequence or sequences of  claim 412 . 
     
     
         415 . The host cell of  claim 414 , wherein said host cell is a mammalian, bacterial, fungal, yeast, avian or insect cell. 
     
     
         416 . The host cell of  claim 415  which comprises a filamentous fungi or a yeast optionally selected from include  Pichia pastoris, Pichia finlandica, Pichia trehalophila, Pichia koclamae, Pichia membranaefaciens, Pichia minuta  ( Ogataea minuta, Pichia lindneri ),  Pichia opuntiae, Pichia thermotolerans, Pichia salictaria, Pichia guercuum, Pichia pijperi, Pichia stiptis, Pichia methanolica, Pichia  sp.,  Saccharomyces cerevisiae, Saccharomyces  sp.,  Hansenula polymorpha, Kluyveromyces  sp.,  Kluyveromyces lactic, Candida albicans, Aspergillus nidulans, Aspergillus niger, Aspergillus oryzae, Trichoderma reesei, Chrysosporium lucknowense, Fusarium  sp.,  Fusarium gramineum, Fusarium venenatum, Physcomitrella patens  and  Neurospora crassa. Pichia  sp., any  Saccharomyces  sp.,  Hansenula polymorpha , any  Kluyveromyces  sp.,  Candida albicans , any  Aspergillus  sp.,  Trichoderma reesei, Chrysosporium lucknowense , any  Fusarium  sp. and  Neurospora crassa.    
     
     
         417 . The host cell of  claim 415 , wherein said host cell is a mammalian cell optionally selected from a CHO, COS, BHK, myeloma, monkey kidney CV1 line transformed by SV40 (COS-7, ATCC CRL 1651); human embryonic kidney line (293 or 293 cells subcloned for growth in suspension culture), mouse sertoli cell; human lung cell; human liver cell, or a mouse mammary tumor cell. 
     
     
         418 . A method of making the antibody or antibody fragment according to  claim 406 , by expressing nucleic acids which encode for the expression of said antibody or antibody fragment in a recombinant host cell. 
     
     
         419 . The method of  claim 418 , wherein the host cell is selected from a bacteria, yeast, fungi, insect cell, plant cell, avian cell, or mammalian cell optionally selected from filamentous fungi, which may optimally be polyploidal. 
     
     
         420 . The method of  claim 419 , wherein said a yeast or a filamentous fungi include  Pichia pastoris, Pichia finlandica, Pichia trehalophila, Pichia koclamae, Pichia membranaefaciens, Pichia minuta  ( Ogataea minuta, Pichia lindneri ),  Pichia opuntiae, Pichia thermotolerans, Pichia salictaria, Pichia guercuum, Pichia pijperi, Pichia stiptis, Pichia methanolica, Pichia  sp.,  Saccharomyces cerevisiae, Saccharomyces  sp.,  Hansenula polymorpha, Kluyveromyces  sp.,  Kluyveromyces  lactic,  Candida albicans, Aspergillus nidulans, Aspergillus niger, Aspergillus oryzae, Trichoderma reesei, Chrysosporium lucknowense, Fusarium  sp.,  Fusarium gramineum, Fusarium venenatum, Physcomitrella patens  and  Neurospora crassa. Pichia  sp., any  Saccharomyces  sp.,  Hansenula polymorpha , any  Kluyveromyces  sp.,  Candida albicans , any  Aspergillus  sp.,  Trichoderma reesei, Chrysosporium lucknowense , any  Fusarium  sp. and  Neurospora crassa  or said host cell is a mammalian cell. 
     
     
         421 . A therapeutic or diagnostic method that comprises the administration of a therapeutic or diagnostically effective amount of at least one antibody or antibody fragment according to  claim 406 , optionally with another diagnostic or therapeutic agent. 
     
     
         422 . The method of  claim 421 , wherein the antibody or antibody fragment is administered by a means selected from buccal, epicutaneous, epidural, inhalation, intraarterial, intracardial, intracerebroventricular, intradermal, intramuscular, intranasal, intraocular, intraperitoneal, intraspinal, intrathecal, intravenous, oral, parenteral, rectally via an enema or suppository, subcutaneous, subdermal, sublingual, transdermal, and transmucosal. 
     
     
         423 . A method of using an antibody or antibody fragment according to  claim 406  to isolate, detect or purify PCSK9 in a sample. 
     
     
         424 . A method of using an antibody or antibody fragment according to  claim 406  to detect the levels of PCSK9 in vivo or ex vivo.