公开(公告)号：US20080241861A1

公开(公告)日：2008-10-02

申请号：US11974794

申请日：2007-10-16

Applicant: John Collinge ,  Anthony R. Clarke ,  Graham S. Jackson

Inventor： John Collinge ,  Anthony R. Clarke ,  Graham S. Jackson

IPC: G01N33/53 ,  C07K14/00 ,  C12P21/04 ,  G01N33/566 ,  C12Q1/00

CPC classification number: A61K49/0058 ,  A61K38/00 ,  A61K51/1018 ,  C07K14/47 ,  C07K16/2872

Abstract: The present invention relates to a method of making a β-form of a prion protein which preferably has more β-sheet than α-helix structure and is soluble in the absence of a denaturant and/or is non-aggregated and exhibits partial resistance to digestion with proteinase K. The invention also relates to use of the β-form in medicine, especially for raising antibodies useful in the treatment and/or diagnosis of prion diseases. The invention also relates to methods of screening for compounds which are capable of inhibiting and/or reversing the conversion of the native α-form of a prion protein to a β-form, and to uses of identified compounds in medicine.

Abstract translation: 本发明涉及一种制备朊蛋白的β型的方法，其优选比α-螺旋结构具有更多的β-折叠，并且在不存在变性剂和/或非聚集的情况下是可溶的，并表现出对 用蛋白酶K消化。本发明还涉及β-形式在药物中的用途，特别是用于产生可用于治疗和/或诊断朊病毒疾病的抗体。 本发明还涉及筛选能够抑制和/或逆转天然α-形式的朊病毒蛋白转化为β型的化合物的方法，以及在药物中使用鉴定的化合物。

公开(公告)号：US06998231B2

公开(公告)日：2006-02-14

申请号：US09778926

申请日：2001-02-06

Applicant: John Collinge

Inventor： John Collinge

IPC: C12Q1/68 ,  C12N15/00 ,  C12N15/63 ,  C12N1/20 ,  C07H21/04

CPC classification number: G01N33/6896 ,  A61K31/435 ,  C12Q1/6883 ,  C12Q2600/156 ,  G01N2800/2828 ,  G01N2800/52

Abstract: The present invention relates to a method for typing a sample of a prion or spongiform encephalopathy disease, a kit suitable for use in such a typing method, a method for identifying infection in an animal and/or tissue of bovine spongiform encephalopathy (BSE), a method for assessing and/or predicting the susceptibility of an animal to BSE, a kit for use in such an assessment and/or prediction method, a method for the treatment of a prion disease, and compounds suitable for such a method.

Abstract translation: 本发明涉及一种用于分选朊病毒或海绵状脑病的样品的方法，适用于这种分型方法的试剂盒，用于鉴定牛海绵状脑病（BSE）的动物和/或组织中的感染的方法， 用于评估和/或预测动物对BSE的敏感性的方法，用于这种评估和/或预测方法的试剂盒，用于治疗朊病毒疾病的方法和适用于该方法的化合物。

公开(公告)号：US07875259B2

公开(公告)日：2011-01-25

申请号：US11140416

申请日：2005-05-27

Applicant: John Collinge ,  Anthony R. Clarke ,  Graham S. Jackson

Inventor： John Collinge ,  Anthony R. Clarke ,  Graham S. Jackson

IPC: A61K49/00 ,  A61K45/00 ,  A61K39/35

CPC classification number: A61K49/0058 ,  A61K38/00 ,  A61K51/1018 ,  C07K14/47 ,  C07K16/2872

Abstract: The present invention relates to a method of making a β-form of a prion protein which preferably has more β-sheet than α-helix structure and is soluble in the absence of a denaturant and/or is non-aggregated and exhibits partial resistance to digestion with proteinase K. The invention also relates to use of the β-form in medicine, especially for raising antibodies useful in the treatment and/or diagnosis of prion diseases. The invention also relates to methods of screening for compounds which are capable of inhibiting and/or reversing the conversion of the native α-form of a prion protein to a β-form, and to uses of identified compounds in medicine.

Abstract translation: 本发明涉及一种制备朊病毒蛋白的方法，其优选地具有比α-螺旋结构更多的片段，并且在不存在变性剂和/或不聚集并且表现出部分 抗蛋白酶K的消化能力。本发明还涉及在医学中使用形式，特别是用于产生用于治疗和/或诊断朊病毒疾病的抗体。 本发明还涉及筛选能够抑制和/或逆转天然α-形式的朊病毒蛋白转化成形式的化合物的方法，以及在药物中使用鉴定的化合物。

公开(公告)号：US06887676B1

公开(公告)日：2005-05-03

申请号：US09958517

申请日：2000-04-07

Applicant: John Collinge ,  Jonathan David Frank Wadsworth

Inventor： John Collinge ,  Jonathan David Frank Wadsworth

IPC: A61K31/095 ,  A61K31/132 ,  A61K31/198 ,  A61K45/00 ,  A61P25/28 ,  C07K14/47 ,  C12Q1/37 ,  G01N33/15 ,  G01N33/50 ,  G01N33/569 ,  G01N33/68 ,  C07K14/00 ,  C12N9/48 ,  C12N9/50 ,  C12Q1/00

CPC classification number: C07K14/47 ,  G01N33/56983 ,  G01N33/6896 ,  G01N2800/2828

Abstract: The invention relates to methods and materials for use in the typing, diagnosis, prevention and/or treatment of prion disease.

Abstract translation: 本发明涉及用于分型，诊断，预防和/或治疗朊病毒疾病的方法和材料。

公开(公告)号：US09028801B2

公开(公告)日：2015-05-12

申请号：US11792686

申请日：2005-12-07

Applicant: Malcolm Andrew Ward ,  John Collinge ,  Graham Stuart Jackson ,  Emma McGregor ,  Nicola Louise Leeds ,  James Campbell ,  Jules Arthur Westbrook ,  Helen Louise Byers

Inventor： Malcolm Andrew Ward ,  John Collinge ,  Graham Stuart Jackson ,  Emma McGregor ,  Nicola Louise Leeds ,  James Campbell ,  Jules Arthur Westbrook ,  Helen Louise Byers

IPC: A61B5/145 ,  G01N33/48 ,  C07K14/805 ,  C07K14/75 ,  C07K14/705 ,  G01N33/68

CPC classification number: G01N33/6896 ,  G01N2800/2828 ,  G01N2800/56 ,  G01N2800/60

Abstract: The invention relates to a method of diagnosis of vCJD in a diagnostic sample of a valid body tissue taken from a human subject, which comprises detecting an increased concentration of a protein in the diagnostic sample, compared with a sample of a control human subject, the protein being: beta-actin (SwissProt Acc. No. P60709), apolipoprotein A-IV precursor (SwissProt Acc. No. P06727); haptoglobin beta-chain consisting of residues 162-406 (SwissProt Acc. No. P00738); haemoglobin beta chain (SwissProt Acc. No. P02023); or alpha-1-antitrypsin (SwissProt Acc. No. P01009); or a decreased concentration of a protein in the diagnostic sample, compared with a sample of a control, normal human subject, the protein being plasma protease (C1) inhibitor precursor (SwissProt Acc. No. P05155); complement component 1, s sub-component (SwissProt Acc. No. P09871); butyrylcholinesterase precursor (SwissProt Acc. No. P06276); complement component C4B (SwissProt Acc. No. P01028); lumican (SwissProt Acc. No. P51884); alpha-fibrinogen precursor (SwissProt Acc. No. P02671); IGHG4 protein (Swiss Prot Acc. No. Q8TC63) or immunoglobulin lambda heavy chain. Other marker proteins are also disclosed.

Abstract translation: 本发明涉及一种诊断样品中vCJD的方法，该方法是从人体受试者获取的有效身体组织的诊断样本中，其与检测样本中的蛋白质的浓度相比较，与对照人受试者相比， 蛋白质是：β-肌动蛋白（SwissProt Acc.P60709），载脂蛋白A-IV前体（SwissProt Acc.Po6727）; 由残基162-406组成的触珠蛋白β链（SwissProt Acc.P00738）; 血红蛋白β链（SwissProt Acc。编号P02023）; 或α-1-抗胰蛋白酶（SwissProt Acc。编号P01009）; 或与对照组，正常人受试者的样品，蛋白质是血浆蛋白酶（C1）抑制剂前体（SwissProt Acc.No.P05155））相比，诊断样品中蛋白质的浓度降低。 补充成分1的子成分（SwissProt Acc。No.P09871）; 丁酰胆碱酯酶前体（SwissProt Acc.Po6276）; 补体成分C4B（SwissProt Acc。No.P01028）; lumican（SwissProt Acc。No. P51884）; α-纤维蛋白原前体（SwissProt Acc。编号P02671）; IGHG4蛋白（Swiss Prot Acc。No.Q8TC63）或免疫球蛋白λ重链。 还公开了其它标记蛋白。

公开(公告)号：US08431526B2

公开(公告)日：2013-04-30

申请号：US13221417

申请日：2011-08-30

Applicant: Vincent Brian Croud ,  Graham Jackson ,  John Collinge

Inventor： Vincent Brian Croud ,  Graham Jackson ,  John Collinge

IPC: C07K14/00

CPC classification number: A61L2/16 ,  A01N37/16 ,  A23L3/3499 ,  A23L3/3508 ,  A23L3/3571 ,  A61L2/186 ,  A61L2202/24 ,  C11D3/386 ,  C11D3/3947 ,  C11D3/48 ,  C11D11/0041 ,  A01N2300/00 ,  A01N25/30 ,  A01N37/46 ,  A01N61/00 ,  A01N63/00 ,  A01N63/02 ,  A01N63/04 ,  A01N65/00

Abstract: The invention relates to compositions and methods for prion degradation, decontamination or disinfection. The composition comprises an oxidizing agent, one or more proteases and a surfactant such as an ionic surfactant/detergent. The method comprises contacting a prion contaminated entity with a prion-degrading composition comprising an effective amount of an oxidizing agent, an effective amount of at least one protease, and an effective amount of a surfactant. The components of the composition may be contacted with a prion-contaminated entity sequentially or simultaneously using an aqueous composition. Typically at least two different proteases are used for optimal efficacy. Preferably the oxidizing agent comprises peracetyl ions or a source thereof. The invention also relates to kits comprising the various reagents.

Abstract translation: 本发明涉及朊病毒降解，去污或消毒的组合物和方法。 组合物包含氧化剂，一种或多种蛋白酶和表面活性剂如离子表面活性剂/洗涤剂。 该方法包括使朊病毒污染的实体与包含有效量的氧化剂，有效量的至少一种蛋白酶和有效量的表面活性剂的朊病毒降解组合物接触。 组合物的组分可以使用水性组合物依次或同时与朊病毒污染的实体接触。 通常使用至少两种不同的蛋白酶来获得最佳疗效。 优选地，氧化剂包括全乙酰离子或其源。 本发明还涉及包含各种试剂的试剂盒。

公开(公告)号：US20080213802A1

公开(公告)日：2008-09-04

申请号：US11792686

申请日：2005-12-07

Applicant: Malcolm Andrew Ward ,  John Collinge ,  Graham Stuart Jackson ,  Emma McGregor ,  Nicola Louise Leeds ,  James Campbell ,  Jules Arthur Westbrook ,  Helen Louise Byers

Inventor： Malcolm Andrew Ward ,  John Collinge ,  Graham Stuart Jackson ,  Emma McGregor ,  Nicola Louise Leeds ,  James Campbell ,  Jules Arthur Westbrook ,  Helen Louise Byers

IPC: G01N33/53 ,  C12Q1/02 ,  C12Q1/46

CPC classification number: G01N33/6896 ,  G01N2800/2828 ,  G01N2800/56 ,  G01N2800/60

Abstract: The invention relates to a method of diagnosis of vCJD in a diagnostic sample of a valid body tissue taken from a human subject, which comprises detecting an increased concentration of a protein in the diagnostic sample, compared with a sample of a control human subject, the protein being: beta-actin (SwissProt Ace. No. P60709), apolipoprotein A-IV precursor (SwissProt Acc. No. P06727); haptoglobin beta-chain consisting of residues 162-406 (SwissProt Acc. No. P00738); haemoglobin beta chain (SwissProt Ace. No. P02023); or alpha-1-antitrypsin (SwissProt Ace. No. P01009); or a decreased concentration of a protein in the diagnostic sample, compared with a sample of a control, normal human subject, the protein being plasma protease (C1) inhibitor precursor (SwissProt Acc. No. P05155); complement component 1, s sub-component (SwissProt Acc. No. P09871); butyrylcholinesterase precursor (SwissProt Acc. No. P06276); complement component C4B (SwissProt Acc. No. P01028); lumican (SwissProt Ace. No. P51884); alpha-fibrinogen precursor (SwissProt Ace. No. P02671); IGHG4 protein (Swiss Prot Ace. No. Q8TC63) or immunoglobulin lambda heavy chain. Other marker proteins are also disclosed.

Abstract translation: 本发明涉及一种诊断样品中vCJD的方法，该方法是从人体受试者获取的有效身体组织的诊断样本中，其与检测样本中的蛋白质的浓度相比较，与对照人受试者相比， 蛋白质是：β-肌动蛋白（SwissProt Ace.No.P60709），载脂蛋白A-IV前体（SwissProt Acc.Po6727）; 由残基162-406组成的触珠蛋白β链（SwissProt Acc.P00738）; 血红蛋白β链（SwissProt Ace。编号P02023）; 或α-1-抗胰蛋白酶（SwissProt Ace.Po1009）; 或与对照组，正常人受试者的样品，蛋白质是血浆蛋白酶（C1）抑制剂前体（SwissProt Acc.No.P05155））相比，诊断样品中蛋白质的浓度降低。 补充成分1的子成分（SwissProt Acc。No.P09871）; 丁酰胆碱酯酶前体（SwissProt Acc.Po6276）; 补体成分C4B（SwissProt Acc。No.P01028）; lumican（SwissProt Ace。No. P51884）; α-纤维蛋白原前体（SwissProt Ace。编号P02671）; IGHG4蛋白（Swiss Prot Ace。No.Q8TC63）或免疫球蛋白λ重链。 还公开了其它标记蛋白。

公开(公告)号：US20080206843A1

公开(公告)日：2008-08-28

申请号：US11977844

申请日：2007-10-26

Applicant: Vincent Brian Croud ,  John Collinge ,  Graham Jackson

Inventor： Vincent Brian Croud ,  John Collinge ,  Graham Jackson

IPC: C11D7/42

CPC classification number: A61L2/16 ,  A01N37/16 ,  A23L3/3499 ,  A23L3/3508 ,  A23L3/3571 ,  A61L2/186 ,  A61L2202/24 ,  C11D3/386 ,  C11D3/3947 ,  C11D3/48 ,  C11D11/0041 ,  A01N2300/00 ,  A01N25/30 ,  A01N37/46 ,  A01N61/00 ,  A01N63/00 ,  A01N63/02 ,  A01N63/04 ,  A01N65/00

Abstract: The invention relates to compositions and methods for prion degradation, decontamination or disinfection. The composition comprises an oxidizing agent, one or more proteases and a surfactant such as an ionic surfactant/detergent. The method comprises contacting a prion contaminated entity with a prion-degrading composition comprising an effective amount of an oxidizing agent, an effective amount of at least one protease, and an effective amount of a surfactant. The components of the composition may be contacted with a prion-contaminated entity sequentially or simultaneously using an aqueous composition. Typically at least two different proteases are used for optimal efficacy. Preferably the oxidizing agent comprises peracetyl ions or a source thereof. The invention also relates to kits comprising the various reagents.

Abstract translation: 本发明涉及朊病毒降解，去污或消毒的组合物和方法。 组合物包含氧化剂，一种或多种蛋白酶和表面活性剂如离子表面活性剂/洗涤剂。 该方法包括使朊病毒污染的实体与包含有效量的氧化剂，有效量的至少一种蛋白酶和有效量的表面活性剂的朊病毒降解组合物接触。 组合物的组分可以使用水性组合物依次或同时与朊病毒污染的实体接触。 通常使用至少两种不同的蛋白酶来获得最佳疗效。 优选地，氧化剂包括全乙酰离子或其源。 本发明还涉及包含各种试剂的试剂盒。

公开(公告)号：US06534036B1

公开(公告)日：2003-03-18

申请号：US09431887

申请日：1999-11-02

Applicant: John Collinge ,  Anthony R. Clarke ,  Graham S. Jackson

Inventor： John Collinge ,  Anthony R. Clarke ,  Graham S. Jackson

IPC: A61K4900

CPC classification number: A61K49/0058 ,  A61K38/00 ,  A61K51/1018 ,  C07K14/47 ,  C07K16/2872

Abstract: The present invention relates to a method of making a &bgr;-form of a prion protein which preferably has more &bgr;-sheet than &agr;-helix structure and is soluble in the absence of a denaturant and/or is non-aggregated and exhibits partial resistance to digestion with proteinase K. The invention also relates to use of the &bgr;-form in medicine, especially for raising antibodies useful in the treatment and/or diagnosis of prion diseases. The invention also relates to methods of screening for compounds which are capable of inhibiting and/or reversing the conversion of the native &agr;-form of a prion protein to a &bgr;-form, and to uses of identified compounds in medicine.

公开(公告)号：US6090550A

公开(公告)日：2000-07-18

申请号：US860050

申请日：1997-08-28

Applicant: John Collinge ,  David Thornley

Inventor： John Collinge ,  David Thornley

IPC: C12N15/09 ,  C12Q1/68 ,  G06F17/30 ,  C12P19/34 ,  G01N33/00

CPC classification number: C12Q1/6869 ,  Y10T436/143333

Abstract: A method of automatically sequencing DNA comprises repeatedly determining the next base in the sequence as a function not only of a physical measurement made at that position, but also as a function of previously-determined near-by bases in the same sequence. Typically, a computer algorithm is used which predicts the value of the expected measurement at a given position based upon a knowledge of the bases in previous and/or subsequent positions. The predicted measurement is then compared with the actual measurement, and the base chosen at that position is the base which minimizes the accumulated error measure for the entire sequence. The preferred algorithm, which may be parallel or sequential, preferably includes physical modelling of the replication effect and of the fluorescence effect.

Abstract translation: PCT No.PCT / GB95 / 03026 Sec。 371日期1997年8月28日 102（e）日期1997年8月28日PCT提交1995年12月22日PCT公布。 公开号WO96 / 20286 日期1996年7月4日DNA自动测序DNA的方法包括重复地确定序列中的下一个碱基，作为不仅在该位置进行的物理测量的功能，而且还作为先前确定的相邻碱基的函数 序列。 通常，使用计算机算法，其基于在先前和/或后续位置中的基础的知识来预测给定位置处的期望测量值。 然后将预测的测量与实际测量值进行比较，并且在该位置处选择的基数是使整个序列的累积误差测量最小化的基础。 可以是平行或顺序的优选算法优选地包括复制效应和荧光效应的物理建模。