HLAL RDNA CONSTRUCT IN SBC LAL-C CHICKENS- hlal rdna construct in sbc lal-c chicken not applicable

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Heritable construct

1. DESCRIPTION

hLAL rDNA construct integrated at a single site (the SYN LAL-C site in chromosome 6) as a single copy, in a specific, diploid line (SBC LAL-C) of hemizygous and homozygous domestic chickens (Gallus gallus) derived from the lineage progenitor XLL 109, expressing a human lysosomal acid lipase (rhLAL) encoding gene such that rhLAL protein (intended for the treatment of humans) is present in their egg whites.

2. WARNINGS AND PRECAUTIONS

SBC LAL-C animals, or any materials derived from the SBC LAL-C animals, are not intended to enter the human or animal food supply.

3. EFFECTIVENESS

Multiple generations of the SBC LAL-C line have demonstrated genetic consistency as established through genetic tests for the presence of the hLAL rDNA construct, hLAL rDNA DNA sequence fidelity and hLAL rDNA construct integration site consistency. For each generation, phenotypic consistency has been established based on the presence of recombinant human LAL enzyme activity in egg white.

4. ANIMAL SAFETY

Data from the following comparisons of SBC LAL-C to non-GE animals demonstrated a lack of adverse effect for the rDNA construct, or the recombinant human LAL protein, on the SBC LAL-C line:

Mortality1 rates for SBC LAL-C and non-GE animals housed at the same facility. Facility 1 houses both SBC LAL-C and non-GE animals; Facilities 2 and 3 do not house non-GE animals. This dataset includes mortality rates collected at three Alexion animal facilities housing three generations of SBC LAL-C collected over a two-year period.

Table 1: Average Weekly Mortality Rates (Three Facilities)
	Avg. Weekly Mortality (%)	Standard Deviation	Range (%)
Facility 1	0.66	0.40	0-1.74
Facility 2	0.14	0.14	0-0.52
Facility 3	0.25	0.16	0-0.58
Overall for SBC LAL-C	0.45	0.40	0-1.74
Non-GE animals	0.40	0.58	0-2.22

In a study to compare physiological endpoints SBC LAL-C vs. non-GE chickens, blood samples were collected for serological and gross/histological evaluations. No differences between LAL-C and non-GE animals were evident based on the following evaluations: serology and histopathology, including CBC (complete blood count), comprehensive blood chemistry, triglycerides and LDH (lactate dehydrogenase) and histopathological examination of multiple tissues.
No differences in growth (body weight) between LAL-C and non-GE animals were evident. This conclusion is based on a dataset from body weights of SBC LAL-C and non-GE animals collected at 18, 23 and 28 weeks of age.

Table 2: Growth (Body Weight) for LAL-C and Non-GE Animals
LINE	18 Weeks of Age Body Weight (in grams)		23 Weeks of Age Body Weight (in grams)		28 Weeks of Age Body Weight (in grams)
LINE	Mean	Standard Deviation	Mean	Standard Deviation	Mean	Standard Deviation
SBC LAL-C Hens (n=77)	1420	219	1635	202	1732	231
SBC LAL-C Males (n=23)	1815	207	1975	112	2031	131
Non-GE Hens (n=6)	1265	163	1380	171	1375	192
Non-GE Males (n=7)	1569	158	1666	137	1778	68

LAL-C hens produced eggs over a 3-year period at the same average annual rate as non-GE hens housed under the same conditions. These values are also consistent with the 280 eggs per hen produced per year reported for White Leghorn flocks in commercial egg production facilities2.

Table 3: Egg Production Rates for LAL-C and Non-GE Animals
Hen Age (weeks)	25	30	35	40	45	50	55	60	65	70

SBC LAL-C Hens:
* Based on data from eight production rooms at Facilities 1 and 2.
Average*	28.9	58.4	87.4	116.2	145.9	174.4	201.6	224.2	247.5	272.1
Standard Deviation	4.3	4.3	5.3	6.3	7.7	8.7	9.8	11.3	13.7	14.7

Non-GE Hens Facility 1	31	63	93	118	147	173	198	222	248	274

The data for SBC LAL-C compared to non-GE animals demonstrates no significant differences in body weight, mortality, general health status or egg production.

5. LIMITATIONS OF USE

The SBC LAL-C line must be housed in only those Alexion Pharmaceutical, Inc. facilities specified in the approved application.

Manufactured by:

Alexion Pharmaceuticals, Inc.
33 Hayden Avenue
Lexington, MA 02421

[version 001 /2015]

1 Mortality as attributed to animal death and euthanasia for items such as broken legs/wings, cloacal prolapse or other injury.

2 (Austic, 1990, Poultry Production)

HLAL RDNA CONSTRUCT IN SBC LAL-C CHICKENS- hlal rdna construct in sbc lal-c chicken not applicable

hLAL rDNA Construct in SBC LAL-C Chickens by

Drug Labeling and Warnings

Drug Details [pdf]