Claims for Patent: 9,464,320

Summary for Patent: 9,464,320

Title:	Methods for placing, accepting, and filling orders for products and services
Abstract:	Methods and systems for ordering assays which detect SNPs or gene expression are provided. The methods use PCR and RT-PCR procedures. Collections of stock assays are assembled using pre- and post-manufacturing quality control procedures and made available to consumers via the Internet. In addition, custom assays are prepared upon order from the consumer and these assays are also prepared using pre- and post-manufacturing quality control procedures. The assays are then delivered to the consumer.
Inventor(s):	Koehler; Ryan T. (Hayward, CA), Livak; Kenneth J. (San Jose, CA), Stevens; Junko (Menlo Park, CA), De La Vega; Francisco M. (San Mateo, CA), Rhodes; Michael (San Mateo, CA), Bellon; Laurent R. (San Mateo, CA), Williams; Julie (Montara, CA), Madden; Dawn (Half Moon Bay, CA), Gilbert; Dennis A. (San Francisco, CA), Wang; Yu N. (Pittsburgh, PA), Spier; Eugene G. (Palo Alto, CA), You; Xiaoqing (San Mateo, CA), Xu; Lily (San Francisco, CA), Heil; Jeremy (Derwood, MD), Glanowski; Stephen (Great Falls, VA), Winn-Deen; Emily S. (Livermore, CA), McMullen; Ivy (Towson, MD), Smith; Leila G. (Echenevex, FR)
Assignee:	Applied Biosystems, LLC (Carlsbad, CA)
Application Number:	13/458,879
Patent Claims:	1. A method for providing assays to a consumer, comprising: providing a web-based user interface configured to receive an order for one or more assays designed for one or more nucleic acid targets; manufacturing or causing to be manufactured one or more assays designed for said one or more nucleic acid targets, including performing pre-processing selection, designing probes and/or primers directed to one or more sequence regions of said one or more nucleic acid targets, and performing an in silico quality control operation, wherein said performing pre-processing selection comprises identifying sequence regions for the one or more nucleic acid targets that do not contain any single nucleotide polymorphisms and also do not contain any repeat sequences; validating said manufactured one or more assays, including performing a quality control testing for one or more components of said manufactured one or more assays, the quality control testing being based on a measured synthesis yield; and delivering or causing to be delivered to the consumer at least one assay including at least two designed primers in response to the order for said one or more assays from the consumer. 2. A method in accordance with claim 1, wherein identifying sequence regions for the one or more nucleic acid targets comprises utilizing at least one method selected from the group consisting of masking single nucleotide polymorphisms and repeat sequences in at least one expressed transcript or portion thereof to avoid designing probes and/or primers thereon, mapping the at least one expressed transcript or portion thereof against at least two genomic databases to identify discrepancies to avoid designing probes and/or primers thereon, and combinations thereof. 3. A method in accordance with claim 1, wherein identifying sequence regions for the one or more nucleic acid targets comprises masking dinucleotide repeats and masking repeat sequences selected from the group consisting of di nucleotide repeats, tri-nucleotide repeats, Alu restriction site repeats, long interspersed nuclear elements, and short interspersed elements, wherein such masked repeat sequences are avoided when designing the probes and/or primers. 4. A method in accordance with claim 1, wherein said probes and/or primers are designed to conform with T.sub.m and GC content specifications and one or more specifications selected from the group consisting of buffer and salt conditions, oligonucleotide concentration in assay, low secondary structure of oligonucleotide, amplicon size, and low incidence of primer-dimer formation. 5. A method in accordance with claim 4, wherein said probes and/or primers are designed to conform with one or more specifications selected from the group consisting of amplicon size and low incidence of primer-dimer formation. 6. A method in accordance with claim 1, wherein said performing the in silico quality control operation comprises determining quality of designed probes and/or primers utilizing genome BLAST scoring and one or more scoring methods selected from the group consisting of transcript BLAST scoring, scoring size of intron across which a probe spans for multiexon genes, and combinations thereof. 7. A method in accordance with claim 1, wherein the probes and/or primers are designed based on one or more pre-selected scoring criteria comprising one or more of assigning high transcript BLAST scoring for matching to self and no other transcript, assigning high genome BLAST scoring for matching to self and no other genome region, and assigning high scoring for intron size greater than 10 kilobases. 8. A method in accordance with claim 1, wherein designing probes and/or primers directed to one or more sequence regions of said one or more nucleic acid targets further comprises avoiding the inclusion of regions of discrepancy between at least two genomic databases in probe and/or primer sequences. 9. A method in accordance with claim 1, wherein identifying sequence regions for the one or more nucleic acid targets comprises utilizing at least identifying exon-exon boundaries for expressed transcripts of multi-exon genes in order to design probes and/or primers thereon. 10. A method in accordance with claim 1, wherein the quality control testing based on a measured synthesis yield comprises ensuring that each designed probe and/or primer in the manufactured one or more assays has a synthesis yield of 60% (w/w) or greater expressed as the weight of the desired probe and/or primer to the total weight of the synthesized product multiplied by 100. 11. The method of claim 1, wherein the quality control testing based on a measured synthesis yield comprises ensuring that each designed probe and/or primer in the manufactured one or more assays has a synthesis yield of 80% (w/w) or greater expressed as the weight of the desired probe and/or primer to the total weight of the synthesized product multiplied by 100. 12. A method for providing assays to a consumer, comprising: providing a web-based user interface configured to receive an order for one or more custom and/or stock assays for one or more nucleic acid targets; manufacturing or causing to be manufactured one or more custom and/or stock assays for said one or more nucleic acid targets, including performing pre-processing selection, designing a probe and primers directed to one or more sequence regions of said one or more nucleic acid targets, and performing an in silico quality control operation; validating said manufactured one or more custom and/or stock assays, including performing a quality control testing for one or more components of said manufactured one or more custom and/or stock assays based on a measured synthesis yield and a quality control testing for one or more components of said manufactured one or more custom and/or stock assays based on a measured mass indicative of sequence accuracy; and delivering or causing to be delivered to the consumer at least one custom and/or stock assay including at least the designed probe and primers in response to the order for said one or more custom and/or stock assays from the consumer, wherein said probe and primers are designed in accordance with one or more criteria comprising at least avoiding inclusion of both single nucleotide polymorphisms and repeat sequences in probe and/or primer sequences. 13. A method in accordance with claim 12, wherein the one or more criteria further comprise-avoiding inclusion of regions of discrepancy between at least two genomic databases in probe and primers sequences. 14. The method of claim 12, wherein the quality control testing based on a measured synthesis yield comprises ensuring that a designed probe and/or primer in the manufactured one or more custom and/or stock assays has a synthesis yield of 60% (w/w) or greater expressed as the weight of the desired probe and/or primer to the total weight of the synthesized product multiplied by 100, and wherein the quality control testing based on a measured mass indicative of sequence accuracy comprises ensuring that the measured mass of a designed probe and/or primer in the manufactured one or more custom and/or stock assays is not more than about 20% greater or lesser than a calculated mass of the designed probe and/or primer. 15. The method of claim 12, wherein the quality control testing based on a measured synthesis yield comprises ensuring that a designed probe and/or primer in the manufactured one or more custom and/or stock assays has a synthesis yield of 80% (w/w) or greater expressed as the weight of the desired probe and/or primer to the total weight of the synthesized product multiplied by 100, and wherein the quality control testing based on a measured mass indicative of sequence accuracy comprises ensuring that the measured mass of a designed probe and/or primer in the manufactured one or more custom and/or stock assays is not more than about 10% greater or lesser than a calculated mass of the designed probe and/or primer. 16. A method for validating assays to be provided to a consumer, comprising: providing a web-based user interface configured to receive an order for one or more assays designed for one or more nucleic acid targets; manufacturing or causing to be manufactured one or more assays designed for said one or more nucleic acid targets, including performing pre-processing selection, designing probes and/or primers directed to one or more sequence regions of said one or more nucleic acid targets, and performing an in silico quality control operation, wherein said performing pre-processing selection comprises identifying sequence regions for the one or more nucleic acid targets that do not contain any single nucleotide polymorphisms and also do not contain any repeat sequences; and validating said manufactured one or more assays, including performing a quality control testing for one or more components of said manufactured one or more assays, the quality control testing being based on a measured synthesis yield. 17. The method of claim 16, further comprising manufacturing at least one SNP assay and performing functional testing of the manufactured at least one SNP assay by performing PCR reactions against from about 10 to about 20 genomic DNA samples. 18. The method of claim 16, wherein the web-based user interface is further configured to receive an order for at least one gene expression assay from a group of at least 10,000 gene expression assays. 19. The method of claim 18, further comprising manufacturing at least one gene expression assay and performing functional testing of the manufactured at least one gene expression assay by performing PCR against at least 10 human cDNA samples with a transcript detection threshold of less than 35 PCR cycles.

Details for Patent 9,464,320

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132	06/04/1986		2022-01-25
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132			2022-01-25
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	Injection	103132			2022-01-25