OurProteinFactory

Uniform Biological Material Transfer Agreement – MTA

Definitions

1. PROVIDER: Organization providing the ORIGINAL MATERIAL. The name and address of this party will be specified in an implementing letter.
2. PROVIDER SCIENTIST: The name and address of this party will be specified in an implementing letter.
3. RECIPIENT: Organization receiving the ORIGINAL MATERIAL. The name and address of this party will be specified in an implementing letter.
4. RECIPIENT SCIENTIST: The name and address of this party will be specified in an implementing letter.
5. ORIGINAL MATERIAL: The description of the material being transferred will be specified in an implementing letter.
6. MATERIAL: ORIGINAL MATERIAL, and PROGENY. The MATERIAL shall not include: (a) MODIFICATIONS, or (b) other substances created by the RECIPIENT through the use of the MATERIAL which are not MODIFICATIONS, PROGENY, or UNMODIFIED DERIVATIVES.
7. PROGENY: Unmodified descendant from the MATERIAL, such as virus from virus, cell from cell, or organism from organism, DNA/RNA duplicated by DNA/RNA supplied by the PROVIDER, purified or fractionated subsets of the ORIGINAL MATERIAL.
8. UNMODIFIED DERIVATIVES: Substances created by the RECIPIENT which constitute an unmodified functional subunit or product expressed by the ORIGINAL MATERIAL. Some examples include: proteins expressed by DNA/RNA supplied by the PROVIDER, or monoclonal antibodies secreted by a hybridoma cell line.
9. MODIFICATIONS: Substances created by the RECIPIENT which contain/incorporate the MATERIAL, and UNMODIFIED DERIVATIVES.
10. COMMERCIAL PURPOSES: The sale, lease, license, or other transfer of the MATERIAL or MODIFICATIONS to a for-profit organization. COMMERCIAL PURPOSES shall also include uses of the MATERIAL or MODIFICATIONS by any organization, including RECIPIENT, to perform contract research, to screen compound libraries, to produce or manufacture products for general sale, or to conduct research activities that result in any sale, lease, license, or transfer of the MATERIAL or MODIFICATIONS to a for-profit organization. However, industrially sponsored academic research shall not be considered a use of the MATERIAL or MODIFICATIONS for COMMERCIAL PURPOSES per se, unless any of the above conditions of this definition are met.
11. NONPROFIT ORGANIZATION(S): A university or other institution of higher education or an organization any nonprofit scientific or educational organization qualified under a nonprofit organization statute. As used herein, the term also includes government agencies.

Terms and Conditions of this Agreement

1. The PROVIDER retains ownership of the MATERIAL, including any MATERIAL contained or incorporated in MODIFICATIONS.

2. The RECIPIENT retains ownership of: (a) MODIFICATIONS (except that, the PROVIDER retains ownership rights to the MATERIAL included therein), and (b) those substances created through the use of the MATERIAL or MODIFICATIONS, but which are not PROGENY, UNMODIFIED DERIVATIVES or MODIFICATIONS (i.e., do not contain the ORIGINAL MATERIAL, PROGENY, UNMODIFIED DERIVATIVES). If either 2 (a) or 2 (b) results from the collaborative efforts of the PROVIDER and the RECIPIENT, joint ownership may be negotiated.

a) is to be used solely for teaching and academic research purposes;
b) will not be used in human subjects, in clinical trials, or for diagnostic purposes involving human subjects without the written consent of the PROVIDER;
c) is to be used only at the RECIPIENT organization and only in the RECIPIENT SCIENTIST's laboratory under the direction of the RECIPIENT SCIENTIST or others working under his/her direct supervision;
d) will not be transferred to anyone else outside the RECIPIENT organization without the prior written consent of the PROVIDER.

4. The RECIPIENT and the RECIPIENT SCIENTIST agree to refer to the PROVIDER any request for the MATERIAL from anyone other than those persons working under the RECIPIENT SCIENTIST's direct supervision. To the extent supplies are available, the PROVIDER or the PROVIDER SCIENTIST agrees to make the MATERIAL available, under a separate implementing letter to this Agreement or other agreement having terms consistent with the terms of this Agreement, to other scientists (at least those at NONPROFIT ORGANIZATION(S)) who wish to replicate the RECIPIENT SCIENTIST's research; provided that such other scientists reimburse the PROVIDER for any costs relating to the preparation and distribution of the MATERIAL.

a) The PROVIDER and/or the PROVIDER SCIENTIST shall have the right, without restriction, to distribute substances created by the PROVIDER through the use of the ORIGINAL MATERIAL only if those substances are not PROGENY, UNMODIFIED DERIVATIVES, or MODIFICATIONS.
b) Under a separate implementing letter to this Agreement (or an agreement at least as protective of the PROVIDER's rights), the RECIPIENT and/or the RECIPIENT SCIENTIST may distribute substances created by the RECIPIENT through the use of the ORIGINAL MATERIAL only if those substances are not PROGENY, UNMODIFIED DERIVATIVES, or MODIFICATIONS.
c) The PROVIDER and/or the PROVIDER SCIENTIST shall have the right, without restriction, to distribute MODIFICATIONS to NONPROFIT ORGANIZATION(S) for research and teaching purposes only.
d) The PROVIDER and/or the PROVIDER SCIENTIST shall have the right, without restriction, to distribute MATERIAL for COMMERCIAL PURPOSES. It is recognized by the PROVIDER that such COMMERCIAL PURPOSES may NOT require a commercial license from the RECIPIENT and the RECIPIENT has no obligation to grant a commercial license to its ownership interest in the MATERIAL. Nothing in this paragraph, however, shall prevent the PROVIDER from granting commercial licenses under the PROVIDER's intellectual property rights claiming such MATERIAL, or methods of their manufacture or their use.
e) The RECIPIENT and/or the RECIPIENT SCIENTIST shall have the right, without restriction, to distribute MODIFICATIONS for COMMERCIAL PURPOSES. It is recognized by the RECIPIENT that such COMMERCIAL PURPOSES may NOT require a commercial license from the PROVIDER and the PROVIDER has no obligation to grant a commercial license to its ownership interest in the MATERIAL incorporated in the MODIFICATIONS. Nothing in this paragraph, however, shall prevent the RECIPIENT from granting commercial licenses under the RECIPIENT's intellectual property rights claiming such MODIFICATIONS, or methods of their manufacture or their use.

6. The RECIPIENT acknowledges that the MATERIAL is or may be the subject of a patent application. Except as provided in this Agreement, no express or implied licenses or other rights are provided to the RECIPIENT under any patents, patent applications, trade secrets or other proprietary rights of the PROVIDER, including any altered forms of the MATERIAL made by the PROVIDER. In particular, no express or implied licenses or other rights are provided to use the MATERIAL, MODIFICATIONS, or any related patents of the PROVIDER for COMMERCIAL PURPOSES.

7. If the RECIPIENT desires to use or license the MATERIAL for COMMERCIAL PURPOSES, the RECIPIENT agrees, in advance of such use, to negotiate in good faith with the PROVIDER to establish the terms of a commercial license. It is understood by the RECIPIENT that the PROVIDER shall have no obligation to grant such a license to the RECIPIENT, and may grant exclusive or non-exclusive commercial licenses to others, or sell or assign all or part of the rights in the MATERIAL to any third party(ies), subject to any pre-existing rights held by others and obligations to the Federal Government.

8. If the PROVIDER desires to use or license the MODIFICATIONS for COMMERCIAL PURPOSES, the PROVIDER agrees, in advance of such use, to negotiate in good faith with the RECIPIENT to establish the terms of a commercial license. It is understood by the PROVIDER that the RECIPIENT shall have no obligation to grant such a license to the PROVIDER, and may grant exclusive or non-exclusive commercial licenses to others, or sell or assign all or part of the rights in the MODIFICATIONS to any third party(ies), subject to any pre-existing rights held by others and obligations to theGovernment.

9. The PROVIDER is free to file patent application(s) claiming inventions made by the PROVIDER through the use of the MODIFICATIONS but agrees to notify the RECIPIENT upon filing a patent application claiming MATERIAL or method(s) of manufacture or use(s) of the MATERIAL.

10. The RECIPIENT is free to file patent application(s) claiming inventions made by the RECIPIENT through the use of the MATERIAL but agrees to notify the PROVIDER upon filing a patent application claiming MODIFICATIONS or method(s) of manufacture or use(s) of the MATERIAL.

11. Any MATERIAL delivered pursuant to this Agreement is understood to be experimental in nature and may have hazardous properties. The PROVIDER MAKES NO REPRESENTATIONS AND EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESSED OR IMPLIED. THERE ARE NO EXPRESS OR IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR THAT THE USE OF THE MATERIAL WILL NOT INFRINGE ANY PATENT, COPYRIGHT, TRADEMARK, OR OTHER PROPRIETARY RIGHTS.

12. Except to the extent prohibited by law, the RECIPIENT assumes all liability for damages which may arise from its use, storage or disposal of the MATERIAL. The PROVIDER will not be liable to the RECIPIENT for any loss, claim or demand made by the RECIPIENT, or made against the RECIPIENT by any other party, due to or arising from the use of the MATERIAL by the RECIPIENT, except to the extent permitted by law when caused by the gross negligence or willful misconduct of the PROVIDER.

13. This agreement shall not be interpreted to prevent or delay publication of research findings resulting from the use of the MATERIAL or the MODIFICATIONS. The PROVIDER SCIENTIST agrees to provide appropriate acknowledgment of the source of the MODIFICATIONS in all publications. The RECIPIENT SCIENTIST agrees to provide appropriate acknowledgment of the source of the MATERIAL in all publications.

14. The PROVIDER agrees to use the MODIFICATIONS in compliance with all applicable statutes and regulations, including Public Health Service and National Institutes of Health regulations and guidelines such as, for example, those relating to research involving the use of animals or recombinant DNA. The RECIPIENT agrees to use the MATERIAL in compliance with all applicable statutes and regulations, including Public Health Service and National Institutes of Health regulations and guidelines such as, for example, those relating to research involving the use of animals or recombinant DNA.

i) if termination should occur under 15(a), the RECIPIENT shall be bound to the PROVIDER by the least restrictive terms applicable to the MATERIAL obtained from the then-available resources; and
ii) if termination should occur under 15(b) or (d) above, the RECIPIENT will discontinue its use of the MATERIAL and will, upon direction of the PROVIDER, return or destroy any remaining MATERIAL. The RECIPIENT, at its discretion, will also either destroy the MODIFICATIONS or remain bound by the terms of this agreement as they apply to MODIFICATIONS; and
iii) In the event the PROVIDER terminates this Agreement under 15( c) other than for breach of this Agreement or for cause such as an imminent health risk or patent infringement, the PROVIDER will defer the effective date of termination for a period of up to one year, upon request from the RECIPIENT, to permit completion of research in progress. Upon the effective date of termination, or if requested, the deferred effective date of termination, RECIPIENT will discontinue its use of the MATERIAL and will, upon direction of the PROVIDER, return or destroy any remaining MATERIAL. The RECIPIENT, at its discretion, will also either destroy the MODIFICATIONS or remain bound by the terms of this agreement as they apply to MODIFICATIONS.

16.Paragraphs 6, 11 and 12 shall survive termination.

17.The MATERIAL is provided at no cost, or with an optional transmittal fee solely to reimburse the PROVIDER for its preparation and distribution costs. If a fee is requested by the PROVIDER, the amount will be indicated in an implementing letter. Main Text Ends Here.

RECIPIENT: Kangma-Healthcode (Shanghai) Biotech Co. Ltd.
RECIPIENT SCIENTIST: Rongrong Zhan
RECIPIENT ADDRESS: Building 15, Lane 118 Furonghua Road, Shanghai 201321, CHINA
RECIPIENT TEL: 021-58086922
RECIPIENT EMAIL: customer@healthcodon.com

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Cell-Free Made 2019-nCoV Virus Proteins

Supported by the world-leading Cell-Free Protein Synthesis (CFPS) technology D2P, OurProteinFactory now offers Cell-Free expressed 25 proteins from the 2019-nCoV coronavirus. Expressed in ProteinFactory Standard package, His-Monster beads purified, His- and/or eGFP-tagged, spike proteins (S1, S2, S-RBD), N protein, M protein, E protein, 3C-Like Protease, RdRp etc. are all in stock.

基于世界领先的无细胞蛋白质合成（Cell-Free Protein Synthesis CFPS）技术 D2P 的支持下，OurProteinFactory 现提供来自2019-nCoV冠状样病毒的，通过无细胞表达制造的25种蛋白质。以 ProteinFactory Standard 标准装表达，His-Monster beads 磁珠纯化，具有 His- 和/或 eGFP- 标签的，多种病毒蛋白如：刺突蛋白（S1，S2，S-RBD），N蛋白，M蛋白，E蛋白，3C-Like蛋白酶，RdRp等，现货供应。

Using pD2P expression vector, all 2019-nCoV proteins coding sequences are codon-optimized, gene synthesized, no homology to viral RNA, no cell involved, no cross-infectivity to live virus, are available to advance the global COVID-19 research and drug development.

所有2019-nCoV蛋白的DNA编码序列均经过密码子优化，基因合成，使用pD2P载体，完全体外表达，无细胞参与，与活病毒核酸序列无交叉，无感染性，助力于全球冠状样病毒疫情监测、防御和治疗的研发。

The 2019-nCoV RNA (29903 bases) encodes 15 Open Reading Frames (ORFs)。Among them, orf1ab is the longest (21330 bases). During protein translation, a codon frame-shift (at position 13468) results in producing two polyproteins as pp1a, pp1ab. [2] These polyproteins are cleaved into 15 proteins. The entire 2019-nCoV RNA encodes 28 proteins in total.

2019-nCoV冠状样病毒RNA（29903个碱基）共含有15个开放阅读框（ORFs)。orf1ab 长度最长（21330 个碱基）。orf1ab 翻译时通过一个中部密码子翻译框位移 (位于13468位)，产生两个大的多体蛋白：pp1a和pp1ab。[2] 这些多体蛋白被分别剪切，形成共1 5种蛋白质。整个2019-nCoV病毒RNA共编码28种蛋白质。

The following protein analysis is based on the most up-to-date 2019-nCoV genome sequence Refseq: NC_045512. [1]

以下蛋白质分析基于NCBI数据库中最新更新的2019-nCoV基因组序列，Refseq: NC_045512. [1]

N: Nucleocapsid phosphoprotein

Function: Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane protein M. Plays an important role in enhancing the efficiency of subgenomic viral RNA transcription as well as viral replication.

Genome location

Amino Acids

MW (KDa)
28274-29530

419

45.64

3CLp: 3C-Like Protease

Function: also named as Mpro (Main Protease), cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN]. Also able to bind an ADP-ribose-1''-phosphate (ADRP).

Genome location

Amino Acids

MW (KDa)
10550-10972

306

33.80

NendoU: Uridylate-specific endoribonuclease

Function: Mn2+-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.

Genome location

Amino Acids

MW (KDa)
19621-20658

346

38.82

2OMT: 2'-O-methyltransferase

Function: Methyltransferase that mediates mRNA cap 2'-O-ribose methylation to the 5'-cap structure of viral mRNAs. N7-methyl guanosine cap is a prerequisite for binding of nsp16. Therefore plays an essential role in viral mRNAs cap methylation which is essential to evade immune system.

Genome location

Amino Acids

MW (KDa)
20659-21552

298

33.33

Nsp1: Host translation inhibitor NSP1

Function: Inhibits host translation by interacting with the 40S ribosomal subunit. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. Viral mRNAs are not susceptible to nsp1-mediated endonucleolytic RNA cleavage thanks to the presence of a 5'-end leader sequence and are therefore protected from degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response.

Genome location

Amino Acids

MW (KDa)
266-805

180

19.78

Nsp2: Non-Structural Protein 2

Function: May play a role in the modulation of host cell survival signaling pathway by interacting with host PHB and PHB2. Indeed, these two proteins play a role in maintaining the functional integrity of the mitochondria and protecting cells from various stresses.

Genome location

Amino Acids

MW (KDa)
806-2719

638

70.52

Nsp7: Non-Structural Protein 7

Function: acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.

Genome location

Amino Acids

MW (KDa)
11843-12091

83

9.24

Nsp8: Non-Structural Protein 8

Function: Forms a hexadecamer with Nsp7 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.

Genome location

Amino Acids

MW (KDa)
12092-12685

198

21.89

Nsp9: Non-Structural Protein 9

Function: May participate in viral replication by acting as a ssRNA-binding protein.

Genome location

Amino Acids

MW (KDa)
12685-13024

113

12.38

Nsp10: Non-Structural Protein 10

Function: Plays a pivotal role in viral transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16 2'-O-methyltransferase activities. Therefore plays an essential role in viral mRNAs cap methylation.

Genome location

Amino Acids

MW (KDa)
13025-13441

139

14.79

Table 1. 2019-nCoV Viral Protein List

Protein\Residue Number

Abbrev.

Amino Acids

MW (KDa)
Host translation inhibitor NSP1

Nsp1

180

19.78
Non-structural protein 2

Nsp2

638

70.52
Papain-like proteinase

PL-Pro

1945

217.28
Non-structural protein 4

Nsp3

500

56.19
3C-like proteinase

3CLp

306

33.8
Non-structural protein 6

Nsp6

290

33.04
Non-structural protein 7

Nsp7

83

9.24
Non-structural protein 8

Nsp8

198

21.89
Non-structural protein 9

Nsp9

113

12.38
Non-structural protein 10

Nsp10

139

14.79
RNA-directed RNA polymerase

RdRp

932

106.23
Helicase

Hel

601

66.86
Guanine-N7 methyltransferase

ExoN

527

59.82
Uridylate-specific endoribonuclease

NendoU

346

38.82
2'-O-methyltransferase

2OMT

298

33.33
Spike glycoprotein (S)

S

1273

141.2
orf 3a

orf3a

275

31.01
Envelope protein (E)

E

75

8.27
Membrane glycoprotein (M)

M

222

25.15
orf 6

orf6

61

7.27
orf 7a

orf7a

121

13.75
orf 7b

orf7b

43

5.11
orf 8

orf8

121

13.83
Nucleocapsid phosphoprotein (N)

N

419

45.64
orf 9

orf9

97

10.80
orf 10

orf10

38

4.45
orf 14

orf14

73

8.05

The sequence lists were last updated Wednesday Feb 18 10:45 2020 EST, and are updated as additional sequences are released. The table content is available for download.

References.

1. Wuhan seafood market pneumonia virus isolate Wuhan-Hu-1, complete genome. NCBI Reference Sequence: NC_045512.2

https://www.ncbi.nlm.nih.gov/nuccore/179817425

2. Durai, P., Batool, M., Shah, M. et al. Middle East respiratory syndrome coronavirus: transmission, virology and therapeutic targeting to aid in outbreak control. 2015 Exp Mol Med 47, e181. PMC4558490

3. Experiments performed by NC Zhang, YL Zhao, XL Yang, Xue Y; Data Analysis by TT Hang, NC Zhang, XD Xu, ZN Huang, XQ Ju, M Guo, Kangma-Healthcode.com

4. Full Cell-Free Made Proteins of 2019-nCoV Information can be found on OurProteinFactory.com/2019-nCoV/protein