1. 1 1 AIPLA Firm Logo American Intellectual Property Law Association More Fun with §101 – A Prosecution Perspective for Biotechnology Derived Innovation Roy P. Issac, Ph.D., J.D. IP Practice in Japan – Pre-Meeting at AIPLA Mid-Winter Institute Orlando, Florida January 27, 2015

2. 2 2 AIPLA Firm Logo Disclaimer This presentation is intended for educational purposes only. It is not intended to convey legal advice pertaining to any particular situation and is not a substitute for legal advice.

3. 3 3 AIPLA Firm Logo USPTO Guidance: A Streamlined Approach Product claims– Apply the markedly different characteristics test (Chakrabarty test) –If the claims do not meet the Chakrabarty test, apply the significantly more test from Myriad. Process/Method claims–Apply the Mayo/ Alice test Well-understood Routine Conventional Inventive concept Significantly more

4. 4 4 AIPLA Firm Logo Myriad v. Ambry Uses the Same Bifurcated Approach Soon after the PTO Guidance was published, the Federal Circuit’s opinion in Myriad v. Ambry was issued. Case involved product claims directed to primers and method claims directed to screening for BRCA1 mutation by comparing a patient’s gene sequence with a germline BRCA sequence. Both sets of claims were held patent ineligible. The Court applied the Chakrabarty approach for primers and the Mayo/Alice approach for the method claims.

5. 5 5 AIPLA Firm Logo PTO Guidance: Focus on pre-emption Determine whether an element in the claim directed to a law of nature, natural phenomenon or abstract idea will tie-up the subject matter and pre- empt others from using the judicial exception. Argue how the additional elements in the claim limit the law of nature, natural phenomenon or abstract idea such that not all uses are pre- empted.

6. 6 6 AIPLA Firm Logo PTO Guidance: For products, apply the markedly different characteristics test Dissection Analysis: The markedly different characteristics test is applied to the nature-based product limitations, not for the claim as a whole. However, care should be taken not to overly extend the markedly different characteristics analysis to products that when viewed as a whole are not nature-based. Changes that are incidental to isolation is not enough. E.g. A claim directed to an artificial hip prosthesis coated with a naturally occurring mineral is not an attempt to tie up the mineral. Here, the claim is analyzed as a whole and determined that the prosthesis when viewed as a whole is not nature-based.

7. 7 7 AIPLA Firm Logo PTO Guidance: Markedly Different Characteristics Difference in structure, function and/or other properties Even a small change can result in markedly different characteristics. Purified or isolated products will be eligible when there is a resultant change in characteristics sufficient to show a marked difference. Biological/ pharmaceutical function or activities Chemical or physical properties Phenotype including functional and structural characteristics

8. 8 8 AIPLA Firm Logo Examples of Nature-Based Products That Will Likely Meet the Markedly Different Characteristics Test Genetically modified organisms (Diamond v. Chakrabarty) –Organisms that have been modified to be genetically different from any natural organism such as e.g. insertion of vectors encoding and expressing one or more exogenous genes. –Organisms that have been modified to be biologically or phenotypically different from any natural organism in the absence of genetic engineering e.g. organisms subjected to different growth conditions resulting in some phenotypic difference or cloned animals having a phenotypic difference such as altered telomeres.

9. 9 9 AIPLA Firm Logo Examples of Nature-Based Products That Will Likely Meet the Markedly Different Characteristics Test cDNA (AMP v. Myriad Sup. Ct. 2013) –Nucleic Acids Non-naturally occurring nucleic acid sequences of a native sequence wherein one or more nucleotides have been modified (e.g. tagged nucleic acids, modified bases), deleted, inserted, substituted) such that there is no naturally occurring counterpart. Codon optimized nucleic acid sequences of native nucleic acid sequences so long as the codon optimized sequence is not identical to any native sequence. Nucleic acids having modified internucleotide linkages (e.g. phosphorothioate internucleotide linkages). Vectors that are not identical to naturally occurring plasmids.

10. 10 AIPLA Firm Logo –Proteins Non-naturally occurring crystal structures of natural proteins Non-naturally occurring glycosylation of natural proteins Unglycosylated forms of natural proteins (such as a eukaryotic protein produced in a prokaryotic cell). Non-naturally occurring amino acid sequences of natural proteins resulting from e.g. amino acid substitution, insertion deletion, or presence of a non-naturally occurring or chemical modified amino acid. Non-naturally occurring fusion proteins (e.g. recombinantly produced fusion proteins of two different genes not otherwise found fused together in nature). Circularly permuted proteins (e.g. wherein the amino acid structure of a proteins is altered to provide a new N- and C-terminus). Examples of Nature-Based Products That Will Likely Meet the Markedly Different Characteristics Test

11. 11 AIPLA Firm Logo Examples of Nature-Based Products That Will Likely Meet the Markedly Different Characteristics Test –Cells Cells that are genotypically different from any naturally occurring cell Cells that are phenotypically different from any naturally occurring cell Combinations of naturally occurring cells and unnaturally occurring cells resulting in different biological properties of the combination. Hybrid plants (J. E. M. Ag Supply v. Pioneer Hi-Bred Sup. Ct. 2001)

12. 12 AIPLA Firm Logo PTO Guidance: Significantly More If the markedly different characteristics test cannot be met for the claim element directed to nature-based product, apply the significantly more test from Myriad. Do additional elements add significantly more? Is there an element or a combination of elements sufficient to ensure that the claims amount to significantly more than the judicial exception?

13. 13 AIPLA Firm Logo PTO Guidance: Significantly More What types of additional elements will be considered sufficient to meet the significantly more test is not clear. It is also not clear whether conventional elements can meet the significantly more standard. –For instance, will buffers or carriers in a pharmaceutical formulation be considered sufficient to meet the significantly more standard for a formulation containing a nature-based product.

14. 14 AIPLA Firm Logo Does any element, or combination of elements, in the claim is sufficient to ensure that the claim amounts to significantly more than the judicial exception. –Here the claim elements are analyzed by dissecting the judicial exception out of the claim and determining if the additional elements add sufficiently more. Inventive concept: Does the claim as a whole amount to significantly more than the exception itself? –Claim is analyzed as a whole. –“It is important to consider the claim as a whole. Individual elements viewed on their own may not appear to add significantly more to the claim, but when combined may amount to significantly more than the exception.” PTO Guidance: Method Claims

15. 15 AIPLA Firm Logo Back to the Myriad v. Ambry Decision The Court held that claims directed to short single stranded DNA primers were not patent eligible since they were “structurally identical to the ends of DNA strands found in nature.” In case of screening method claims, the Court determined that the additional elements apart from the DNA sequence itself were directed to “well-understood, routine and conventional activity.”

16. 16 AIPLA Firm Logo Myriad v. Ambry: Primers Primers are not distinguishable from the isolated DNA found patent-ineligible in Myriad. Structurally identical to the ends of DNA strands found in nature. No weight given to the fact that the sequences are synthetically replicated. Separating DNA from its surrounding genetic material is not an act of invention. Myriad argued that primers have fundamentally different function than when the sequence is part of the DNA strand.

17. 17 AIPLA Firm Logo However, the Court found that the naturally occurring sequences do not perform a significantly new function. “A DNA structure with a function similar to that found in nature can only be patent eligible as a composition of matter if it has a unique structure, different from anything found in nature.” Myriad v. Ambry: Primers

18. 18 AIPLA Firm Logo Claim 7: A method for screening germline of a human subject for an alteration of a BRCA1 gene which comprises comparing germline sequence of a BRCA1 gene or BRCA1 RNA from a tissue sample from said subject or a sequence of BRCA1 cDNA made from mRNA from said sample with germline sequences of wild-type BRCA1 gene, wild-type BRCA1 RNA or wild-type BRCA1 cDNA, wherein a difference in the sequence of the BRCA1 gene, BRCA1 RNA or BRCA1 cDNA of the subject from wild-type indicates an alteration in the BRCA1 gene in said subject[,] wherein a germline nucleic acid sequence is compared by hybridizing a BRCA1 gene probe which specifically hybridizes to a BRCA1 allele to genomic DNA isolated from said sample and detecting the presence of a hybridization product wherein a presence of said product indicates the presence of said allele in the subject. “Do the patent claims add enough to their statements of the correlations to allow the processes they describe to qualify as patent-eligible processes that apply natural laws?” Myriad v. Ambry: Screening Method Claims

19. 19 AIPLA Firm Logo Are “the remaining elements, either in isolation or combination with the other non-patent-ineligible elements, sufficient to “transform the nature of the claim” into a patent-eligible application.” Abstract mental steps are not enough. –Compare –Analyze –Determine The first paragraph of the claim is directed to patent ineligible abstract idea of comparing BRCA sequences and determining the existence of alterations. Myriad v. Ambry: Screening Method Claims

20. 20 AIPLA Firm Logo Methods directed to identification of alterations of the gene, require merely comparing the patient’s gene with the wild- type and identifying any differences. The number of covered comparisons is unlimited. The covered comparisons are not restricted by the purpose of the comparison or the alteration detected. Myriad v. Ambry: Screening Method Claims

21. 21 AIPLA Firm Logo The second paragraph of the claim adding particular mechanisms of comparison are analyzed to see if they transform the claim into a patent-eligible application. Additional elements –Hybridizing a BRCA gene probe –Detecting the presence of a hybridization product –Amplification of BRCA1 gene –Sequencing amplified nucleic acids Additional elements “do not add enough to make the claims as a whole patent-eligible.” Myriad v. Ambry: Screening Method Claims

22. 22 AIPLA Firm Logo Additional elements are not enough because, they “set forth well-understood, routine and conventional activity engaged in by scientists at the time of Myriad’s applications.” Myriad v. Ambry: Screening Method Claims

23. 23 AIPLA Firm Logo Back to PTO Guidance: Examples of Nature-Based Products That Meet Patent Eligibility Requirements Combinations of nature-based products that exhibit new functionality or characteristics –Gunpowder where new functional characteristics of explosiveness is not present in individual ingredients. Combinations of nature-based product with additional agents that provide additional characteristics –E.g. Pomelo juice with added preservatives. Formulations with nature-based product –E.g., Amazonic acid with solubilizing agent Method of treating cancer with nature-based product –E.g., Treating cancer with amazonic acid.

24. 24 AIPLA Firm Logo Back to PTO Guidance: Examples of Nature-Based Products That Meet Patent Eligibility Requirements Purified proteins –Purified antibiotics –Proteins expressed in recombinant yeast –Proteins with point mutations Genetically modified bacterium Bacterial mixtures –If the combination provides a mixture with additional functional properties. Nucleic acids –At least one substitution or modification compared to that exists in nature.

25. 25 AIPLA Firm Logo Back to PTO Guidance: Examples of Nature-Based Products That Meet Patent Eligibility Requirements Antibodies –E.g. Human antibodies to bacterial protein. Cells –E.g. Isolated human pacemaker cell expressing marker Z

26. 26 AIPLA Firm Logo Take Home Points Product claims are largely governed by the “markedly different characteristics” test. Determine when to analyze the claim as a whole and when to focus on the nature-based product element. Have a series of narrow claims that add additional claim elements that specify methods of characterizing, comparing etc. Determine if the changes to a nature-based product is “merely incidental to isolation.” AMP v. Myriad may be limited to cases where the changes for a nature-based product are those “merely incidental to isolation.”

27. 27 AIPLA Firm Logo Acknowledgements Carolyn Elmore, Esq. Darlene Vanstone, Esq. Mahreen Hoda, Esq.

28. 28 AIPLA Firm Logo Questions? Roy P. Issac, Ph.D., J.D. Elmore Patent Law Group, P.C. 484 Groton Rd. Westford, MA 01886 978.251.3501 rissac@elmorepatents.com Name