Evolving patterns in a collaboration network of global R&D on monoclonal antibodies

Figures & data

Table 1. Topological properties in 6 static snapshots of the collaboration network.

Year	Nodes	Edges	Average degree	Maximum degree	Average weighted degree	Maximum weighted degree	Average path length	Network diameter	Average clustering coefficient^1
1989	20	14	1.4	5	1.6	7	1.61	3	—
1994	103	89	1.73	10	2.08	12	7.60	17	—
1999	178	189	2.12	17	2.32	18	4.66	14	0.065
2004	352	443	2.52	40	3.09	49	4.55	11	0.055
2009	453	615	2.72	53	3.35	71	4.21	11	0.059
2014	537	760	2.83	54	3.43	76	4.08	10	0.067

¹ No clustering existed in 1989 and 1994.

Figure 1. Collaborative project distribution in each year.

Figure 2. Collaboration network in the years: (A) 1989; (B) 1994; (C) 1999; (D) 2004; (E) 2009; (F) 2014. The main component of the network at each time point is displayed, except the one in 1989 (A) that shows the whole network. In the network, nodes denote the organizations involved in collaborative relationships and are represented as edges. Node size is scaled to the number of edges an organization has (only comparable within the network at a specific time point). The thickness of edges represents the frequency between 2 nodes. Loops, referring to edges that share the head and the end, are eliminated from data collection. The colors of nodes represent different forms of organizations: the purple represents pharmaceutical companies; the green represents DBFs; the yellow represents PROs; and the gray represents other forms. The edges are also colored according to the collaboration modes between nodes in terms of their specific organizational forms, with magenta between 2 pharmaceutical companies; blue between a pharmaceutical company and a DBF; light cyan between 2 DBFs; orange between a pharmaceutical company and a PRO; brick red between a DBF and a PRO; and gray between others.

Figure 3. Distributions of different kinds of participants and varying relationships among them over time.

Figure 4. The cumulative normalized degree of the top 5 players with the highest degree over the 6 snapshots of the collaboration network. Organizations with an asterisk are large pharmaceutical companies.

Figure 5. (A) The number of collaborative projects with identified technological profiles that launched every 2 y. (B) The number of relationships changed by M&A activities every 2 y.

Table 2. The basic technological innovation profiles of some DBFs.

Weighted degree^1	Organization	Technology/Platform	Proportion of platform involvement^2	Key patents^3	Year patent issued^4	Description
49	Medarex	UltiMab® platform	64.6%	EP0546073, US6111166	1997, 2000	Transgenic mouse producing high-affinity fully human antibodies for a wide range of antigens
30	Abgenix	XenoMouse® technology	83.3%	US6150584, US6657103	2000, 2003	Transgenic mice rapidly generating fully human antibody product candidates to disease targets
21	MorphoSys	Human Combinatorial Antibody Library (HuCAL®)	100%	US6300064	2001	Rapid access to fully human antibodies
18	Cambridge Antibody technology	Phage-antibody library	38.9%	US5969108	1999	Phage display systems used to rapidly isolate human monoclonal antibodies
17	PDL BioPharma	SMART® technology	47.1%	US5530101	1996	Converting murine antibody into a humanized antibody better suited for therapeutic applications
17	Seattle Genetics	antibody-drug conjugate (ADC) technology	88.2%	US6884869	2005	Harness the targeting ability of antibodies to link cell-killing agents to target cells directly
16	ImmunoGen	Targeted Antibody Payload (TAP) technology	66.7%	US5208020	1993	Deliver a highly potent cytotoxic agent to cancer cells
11	Dyax	Phage display technology	81.8%	US5837500	1998	Generating human antibodies by phage display technology
11	XOMA	Human Engineering™ (HE™) technique	54.5%	US5766886	1998	Produce humanized antibodies by modifying antibody variable regions

¹ Weighted degree were collected from the collaboration network in the year 2004.

² Proportion of partnerships that involved platform in the organization's all the partnerships in the year 2004.

³ Mainly United States patents are provided.

⁴ Patent issue years correspond to key patents.

Figure 6. The topological shift of DBFs and pharmaceutical companies in the network evolution.

Table 3. Important mergers and acquisitions influencing the position changes in the collaboration network.

Year	Purchaser	Targeting firm	Forms of merging pairs	Promotion on normalized degree^1
2009	Bristol-Myers Squibb	Medarex	Pharma-DBF	0.81
2007	AstraZeneca	MedImmune	Pharma-DBF	0.33
2006	Amgen	Abgenix	DBF-DBF	0.32
2009	Roche	Genentech	Pharma-DBF	0.32
2006	AstraZeneca	Cambridge Antibody Technology	Pharma-DBF	0.27
2011	Teva	Cephalon	Pharma-DBF	0.18
2009	Pfizer	Wyeth	Pharma-Pharma	0.17
2009	Merck & Co	Schering-Plough	Pharma-Pharma	0.17
2011	Johnson & Johnson	Crucell	Pharma-DBF	0.15
2008	Lilly	ImClone Systems	Pharma-DBF	0.15
2012	Amgen	Micromet	DBF-DBF	0.12
2011	Sanofi	Genzyme	Pharma-DBF	0.11

¹ The promotion is calculated by the improvement of purchasers' normalized degree after the M&As occurred.