Understanding Budapest The International Microorganism Depository System - A Practioner's View - Dr. Jürgen Meier

The Biotech-Group at Vossius & Partner Dr. Hans-Rainer Jaenichen Dr. Alexander Schwendemann (Berlin) Dr. Joachim Wachenfeld Dr. Florian Grasser Dr. Friederike Stolzenburg Jennifer Enmon, Ph.D., J.D. Dr. Jürgen Meier Richard M. Enmon, Ph.D., J.D. Dr. Christian Schlörb (Berlin und München) Dr. Lisa Polzien Dr. Werner Bastian (Basel) Dr. Andreas Heiseke Dr. Olaf Malek Dr. Philipp Marchand (Basel) Dr. Roger Abseher Oswin Ridderbusch Dr. Daniel Eisenbarth Dr. Alessandro Tosi Dr. Dirk Günther Dr. Maximilian Kern Dr. Dana Krämer Dr. Ulrich Sentner Dr. Stefan Müller Consultant: Dr. Christian Gugerell © 2017 Vossius & Partner

Successful Patents in the EPO © 2017 Vossius & Partner

The Main Relevance of "Budapest" for the Practitioner "Deposits" can in particular carry the day under Art. 54 EPC (Novelty) Art. 56 EPC (Inventive Step) Art. 83 EPC (Sufficiency) © 2017 Vossius & Partner

A. 83, A. 84 and A. 56 EPC A. 56 EPC: Inventive Step Reproducibility A. 84 EPC: Clarity Clarity A. 83 EPC: Sufficiency of disclosure © 2017 Vossius & Partner

A. 56 EPC “Inventive Step“/“Obviousness“ Problem-Solution-Approach in the EPO identifying the "closest prior art", assessing the technical results (or effects) achieved by the claimed invention when compared with the "closest state of the art" established, defining the technical problem to be solved as the object of the invention to achieve these results, and examining whether or not a skilled person, having regard to the closest state of the art within the meaning of Art. 54(2) EPC, would have suggested the claimed technical features in order to obtain the results achieved by the claimed invention ("White Book", I.D.2) Lack of reproducibility The claim in its full breadth does not solve the technical problem  technical effect must be ignored when assessing inventive step  eventually lack of inventive step (T939/92; T668/94) © 2017 Vossius & Partner

A. 83 EPC – the classic "Onco-Mouse" decision T 18/90 A. 83 EPC: Disclosure of the invention „ The European patent application shall disclose the invention in a manner sufficiently clear and complete for it to be carried out by a person skilled in the art. “ An objection under Art. 83 EPC (as under Art. 57 EPC, T 18/90) can only be based on serious doubts, substantiated by verifiable facts. © 2017 Vossius & Partner

A. 83 EPC Sufficiency of disclosure within the meaning of Art. 83 EPC must be assessed on the basis of the application as a whole – including description and claims and not of the claims alone ("White Book", II.C.2; T 14/83) Substantially any embodiment of the invention, as defined in the broadest claim must be capable of being realized on the basis of the disclosure and the common general knowledge. The person skilled in the art even recognizes and rectifies errors on the basis of such knowledge. ("White Book", II.C.2; T 226/85, T 206/83, T 772/89, ...) This also holds true for embodiments which are defined as" optional" or "preferred" (T 206/13) Lack of Reproducibility Not all embodiments of a claim are enabled (without undue burden!)  Lack of enabling disclosure! © 2017 Vossius & Partner

A. 84 EPC: Clarity A. 84 EPC: Claims „The claims shall define the matter for which protection is sought. They shall be clear and concise and be supported by the description.  “ The claims, which define the matter for which protection is sought, must be clear, meaning not only that a claim must be comprehensible from a technical point of view, but also that it must define clearly all the essential features of the invention (Guidelines, F-IV, 4.5.1; T32/82). T 133/85 “A claim which does not include a feature which is described in the application (on the proper interpretation of the description) as an essential feature of the invention, and which is therefore inconsistent with the description, is not supported by the description for the purpose of Article 84 EPC.” (headnote I). © 2017 Vossius & Partner

The “interplay“ of A. 83 EPC, A. 84 EPC and A The “interplay“ of A. 83 EPC, A. 84 EPC and A. 56 EPC "The technical effect" is a decisive measure (in most Patent Offices)

A. 83 EPC, A. 84 EPC and A. 56 EPC claimed invention is not reproducible/performable Claim language: Reason for Objection under Art. 83 EPC: Person skilled in the art cannot perform invention with his/her general knowledge or the whole content of the application Objection under A. 83 EPC ("Sufficiency") Technical effect in claim [or unclear feature and effect is necessary for understanding the claim] Claim does not comparise the features which are disclosed in the application as solution to the technical problem (does not comprise the essential features) Objection under A. 84 EPC ("Clarity") Technical effect not in claim [and effect is not necessary for understanding the claim] Objection under A. 56 EPC/ Re-formulation of the technical problem ("Inventive Step"/ "Obviousness") In light of the prior art, it is not plausible that the claimed invention solves the posed technical problem © 2017 Vossius & Partner

Patent Deposit under the Budapest Treaty © 2017 Vossius & Partner

What do we need for a medical (use) and/or a biological invention?

How Much Data? In general, there must be a plausible disclosure of the medical use. This is normally accepted if a correlation between the active ingredient and the disease (or the "effect" obtained) has been established (T 163/08). Plausibility can be generated by (in vitro) experiments … and/or “deposits” (Clinical) trials are normally not required, in vitro is enough. © 2017 Vossius & Partner

Quid Pro Quo Purpose of the patent system: Support innovation by granting a monopoly in exchange for an enabling technical teaching (an invention). Technical Board 3.3.08 in T 1452/06: "A basic principle of the patent system is that exclusive rights can only be granted in exchange for a full disclosure of the invention, which includes the need to indicate how to exploit the invention.“ CLEAR! COMPLETE! CREDIBLE! PLAUSIBLE! UNAMBIGUOUS! at the filing (or priority) date!!! © 2017 Vossius & Partner

Clear? Complete? Credible? Plausible? Unambiguous? © 2017 Vossius & Partner

Definition of "Biological Inventions" Deposits, Sequence Information or both?

Complete Technical Teaching? Question: When is an invention fully disclosed or complete enough to justify the monopoly Answers: Given in consideration of Rule 29 (3) EPC: industrial applicability/function. Remember: - The "Plausibility Test" - © 2017 Vossius & Partner

T 1329/04, “Factor-9/JOHN HOPKINS” Technical Board 3.3.8 coined the plausibility test and refused the application for lack of inventive step: The definition of an invention as being a contribution to the art, i.e. as solving a technical problem and not merely putting forward one, requires that it is at least made plausible by the disclosure in the application that its teaching solves indeed the problem it purports to solve. Therefore, even if supplementary post-published evidence may in the proper circumstances also be taken into consideration, it may not serve as the sole basis to establish that the application solves indeed the problem it purports to solve. Conclusion: Unconventional structure and low homology in the absence of experimental evidence is not enough! In microbiological cases or even “sequence” cases, a "deposit" may help to document that at least one solution was provided © 2017 Vossius & Partner

USPTO Patentable Subject Matter/Invention: „Anything Under the Sun Made by Man“ (Congress) ...Really? Diamond v. Chakrabarty, 447 U.S. 303 (1980) (Genetically engineered Pseudomonas) Chief Justice Warren Burger: „Judged in this light, respondent's micro-organism plainly qualifies as patentable subject matter. His claim is ... to a nonnaturally occurring manufacture or composition of matter - a product of human ingenuity.“ ...but now? Mayo v. Prometheus (Mayo Coll. Ser. v. Prometheus Labs, Inc., 132 S. Ct. 1289, 1293 (2012)) AMP v. Myriad Genetics, Inc. (Association of Molecular Pathology v. Myriad Genetics, Inc. , 133 S. Ct. 2107 (2013) © 2017 Vossius & Partner

Any special legal principles for biotech inventions? © 2017 Vossius & Partner

Rule 26 EPC General and Definitions (1) For European patent applications and patents concerning biotechnological inventions, the relevant provisions of the Convention shall be applied and interpreted in accordance with the provisions of this Chapter. Directive 98/44/EC of 6 July 1998 on the legal protection of biotechnological inventions shall be used as a supplementary means of interpretation. (2)  "Biotechnological inventions" are inventions which concern a product consisting of or containing biological material or a process by means of which biological material is produced, processed or used. (3)  "Biological material" means any material containing genetic information and capable of reproducing itself or being reproduced in a biological system. © 2017 Vossius & Partner

Rule 27 EPC Patentable Biotechnological Inventions Biotechnological inventions shall also be patentable if they concern: (a) biological material which is isolated from its natural environment or produced by means of a technical process even if it previously occurred in nature; Thus: The mere existence of a compound in nature does not deprive it of novelty or inventive step! Don’t forget: discovery vs. technical teaching/invention! © 2017 Vossius & Partner

But how does “Budapest” come into play and can someone “steal” my invention? © 2017 Vossius & Partner

Rule 31 (1) EPC Deposit of Biological Material If an invention involves the use of or concerns biological material which is not available to the public and which cannot be described in the European patent application in such a manner as to enable the invention to be carried out by a person skilled in the art, the invention shall only be regarded as being disclosed as prescribed in Article 83 if: a sample of the biological material has been deposited with a recognised depositary institution on the same terms as those laid down in the Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purposes of Patent Procedure of 28 April 1977 not later than the date of filing of the application; the application as filed gives such relevant information as is available to the applicant on the characteristics of the biological material; (c) the depositary institution and the accession number of the deposited biological material are stated in the application  © 2017 Vossius & Partner

Rule 32 EPC Expert Solution Until completion of the technical preparations for publication of the European patent application, the applicant may inform the European Patent Office that, (a) until the publication of the mention of the grant of the European patent or, where applicable, (b) for twenty years from the date of filing, if the application is refused or withdrawn or deemed to be withdrawn, the availability referred to in Rule 33 shall be effected only by the issue of a sample to an expert nominated by the requester. Important consequence: you don’t have to provide “your factory” and/or “crown jewels” to competitors (e.g. hybridomas)! © 2017 Vossius & Partner

Availablitity of Deposits in the US (third parties) I 37 CFR 1.808 A deposit must be made under conditions that assure that: (1) Access to the deposit will be available during pendency of the patent application making reference to the deposit to one determined by the Director to be entitled thereto under § 1.14 and 35 U.S.C. 122 , and (2) Subject to paragraph (b) of this section, all restrictions imposed by the depositor on the availability to the public of the deposited material will be irrevocably removed upon the granting of the patent. © 2017 Vossius & Partner

Availablitity US (third parties) II /comments 1.808 (A) provides that, generally, during the pendency of the *application* the availability of the deposit is limited to those entitled under the confidentiality rules as determined by the Commissioner (note that even though published, the application is still subject to confidentiality rules – protecting copyrighted documents, deposits etc) 1.808 (B) provides that all restrictions on the public availability of the deposit must be lifted on grant, with certain exceptions related to notice (i.e., provided that the request is in writing and/or the requesting party is identified, the deposit must become generally publically available). “Hermetic protection“ © 2017 Vossius & Partner

What is this all good for? Finally, the EXAMPLES…. © 2017 Vossius & Partner

Medical Uses? © 2017 Vossius & Partner

Claims? 1. Beer, comprising at least 20% EtOH. 2. Pharmaceutical composition comprising beer as characterized in claim 1. [new EPC2000] Beer of claim 1 for use in stress release, the treatment of nervous disorders and/or myogelosis. [US: Method of treatment or nervous disorders and/or myogelosis, comprising the administration of beer of claim 1.] A method for the production of beer comprising at least 20% EtOH, said method comprising the fermentation of barely mash with a yeast as deposited under DSMZ 1234567.8. 5. A beer as produced in the method of claim 4. © 2017 Vossius & Partner

Microorganisms! © 2017 Vossius & Partner

T 727/95, “Cellulose/WEYERSHAEUSER” EP-B1 228 779 A microorganism designated Acetobacter and having the ability of microorganisms ATCC 53264, ATCC 53263 and ATCC 53524 to produce a cellulose product under agitated culture conditions and having a frequency of change from cellulose producing forms to cellulose non-producing forms under agitated culture conditions, as determined by the appearance of cellulose non-producing colonies on solid medium, of less than 0.5% over the course of 42-45 generations; which also has, when cultured in accordance with Example XII, the ability to produce cellulose under agitated conditions at an average volumetric productivity of at least 0.1 g/l/hr over a period of time exceeding 70.hours. Actually: the Board said this is a little too broad. © 2017 Vossius & Partner

T 737/96, "Astaxanthin/DSM" 1. A Phaffia rhodozyma yeast cell belonging to the yeast strain deposited under the accession No. 225-87 CBS, or the yeast strain deposited under the accession No. 215-88 CBS, or a mutant or derivative thereof, or a mutant or derivative of the yeast strain deposited under the accession No. 224-87 CBS, which has retained its astaxanthin-producing capability, and when grown under conditions comprising ..., produces astaxanthin in an amount of at least 600 g per g of yeast dry matter, determined by ... . Note: the claim covers the deposited strain or a linear descendant thereof.  © 2017 Vossius & Partner

T 283/11, "MVA-BN/Bavarian Nordic A/S" 1. Modified vaccinia virus Ankara strain MVA-BN deposited at the European Collection of Cell Cultures (ECACC), Salisbury (UK) under number V00083008 and derivatives thereof, wherein said Ankara strain MVA-BN or its derivatives are characterized (i) in being capable of reproductive replication in chicken embryo fibroblasts (CEF) and the Baby hamster kidney cell line BHK but not capable of reproductive replication in the human cell lines human bone osteosarcoma cell line 143B, the human keratinocyte cell line HaCat and human cervix adenocarcinoma cell line HeLa and (ii) by a failure to replicate in vivo in severely immune compromised mice that are incapable of producing mature B and T cells. © 2017 Vossius & Partner

EP-B1 1 989 942 – Morinaga Milk Industry Co., Ltd. Lactococcus lactis: © Kenneth Todar, Ph.D. All rights reserved. - www.textbookofbacteriology.net © 2017 Vossius & Partner

EP-B1 1 989 942 – Morinaga Milk Industry Co., Ltd. Bifidobacterium longum BB536 © 2017 Vossius & Partner

EP-B1 1 989 942 – Morinaga Milk Industry Co., Ltd. A method for producing a fermented milk, comprising performing fermentation using both bacteria belonging to a Bifidobacterium and bacteria belonging to a genus Lactococcus as lactic acid bacteria, wherein the bacteria belonging to the genus Lactococcus have bacteriological properties of: a fermentability which curdles a 10% (W/W) reconstituted skim milk medium when cultivated at a temperature of 25°C to 37°C for 16 hours; Bifidobacterium longum growth-promoting properties which lead a viable count of Bifidobacterium longum of 5 x 108 CFU/g or more, when co-cultivated with Bifidobacterium longum in the 10% (W/W) reconstituted skim milk medium until a pH thereof is 4.4 to 4.6; and Bifidobacterium longum survivability-improving properties during storage, which lead to a survival rate of Bifidobacterium longum of 30% or more, after co-cultivation with Bifidobacterium longum in the 10% (W/W) reconstituted skim milk medium until the pH thereof is 4.4 to 4.6, rapid cooling, and two weeks storage at 10°C. "Technical and functional feature" © 2017 Vossius & Partner

EP-B1 1 989 942 – Morinaga Milk Industry Co., Ltd. The method for producing a fermented milk according to any one of Claims 1 to 3, wherein the bacteria belonging to the genus Lactococcus comprise at least one bacterial strain selected from the group consisting of Lactococcus lactis subsp, lactis MCC852 (FERM BP-10742), Lactococcus lactis subsp. lactis MCC857 (FERM BP-10757), Lactococcus lactis subsp. lactis MCC859 (FERM BP-10744), Lactococcus lactis subsp. lactis MCC865 (FERM BP-10745), and Lactococcus lactis subsp. lactis MCC866 (FERM BP-10746). 8. A fermented milk prepared by the method for producing fermented milk of any one of Claims 1 to 7. "Deposits!!!" © 2017 Vossius & Partner

EP-B1 1 989 942 – Morinaga Milk Industry Co., Ltd. Copyright ©2015 Yakult (Singapore) Pte. Ltd. All Rights Reserved. Copyright © www.actimel.de/Produkte © 2017 Vossius & Partner

Feed & Lifestock – "Lysine" © https://pixabay.com/de/photos/?image_type=&cat=&min_width=&min_height=&q=rinder&order=popular © 2017 Vossius & Partner

The Demand for Essential Amino Acids (e.g. Lysine) © https://pixabay.com/de/photos/hahn/ © https://www.bodybuilding.com/fun/matt88.htm © 2017 Vossius & Partner

Also other producers. Mere examples! © http://www.econovill.com/news/articleView.html?idxno=192238 © http://www.lysine.com/en/ Also other producers. Mere examples! © 2017 Vossius & Partner

EP-B1 2 102 337 – "A Microrganism of Corynebacterium Genus having enhanced L-Lysine Productivity and a Method of producing L-Lysine using the same A microorganism of Corynebacterium genus having enhanced L-lysine productivity by inactivating a gene having repeated aspartate residues in its amino acid sequence, wherein the gene is endogenous NCg11090 gene having the nucleotide sequence represented by SEQ ID NO: 1. The microorganism of Corynebacterium genus according to claim 1, wherein the inactivation is induced by the transformation of the microorganism of Corynebacterium genus with a vector containing a part of the endogenous NCg11090 gene and an antibiotic marker. The microorganism of Corynebacterium genus according to claim 3, wherein the microorganism is Corynebacterium glutamicum KFCC 10881-CO01-0018 (KCCM 10810P) selected by culture in the presence of antibiotics. A method of producing L-lysine comprising the following steps of: producing L-lysine in the cultures or cells by culture of the microorganism of any one of claims 1 to 4; and collecting L-lysine from the cultures.  direct method claim (here lysine!) is protected; "Monsanto" decisions) © 2017 Vossius & Partner

So, what is further patentable under the EPC? © 2017 Vossius & Partner

Antibodies! © 2017 Vossius & Partner

By Reference to Binding Characteristics: T 1300/05 1. A monoclonal antibody generated against a cell-line susceptible to infection by macrophage-tropic HIV-1 isolates, and derived from the HuT 78 T lymphoblastoid cell line, wherein said antibody inhibits HIV-1 envelope glycoprotein mediated membrane fusion between Hela-envJR-FL and said cell-line, but does not inhibit HIV-1 envelope glycoprotein mediated membrane fusion between Hela-envLAI and Sup-T1 cells or between HelaenvLAI and Hela-CD4+ cells. 2. Use of a monoclonal antibody according to claim 1 for the preparation of a medicament for the treatment of HIV-1 infection. © 2017 Vossius & Partner

By Reference to a Method of Making Them: T 30/09 1. An antibody binding exclusively to a PrpSc isoform of the prion protein and recognizing the epitope having the three dimensional conformation provided by the protein sequence … of the PrPSc isoform of the prion protein while not binding to the PrPC form, obtainable by a method comprising the step of immunising an animal with a peptide consisting of the amino acid sequence or … . © 2017 Vossius & Partner

By Reference to DNA or Amino Acid Sequences: T 617/07 20. Monoclonal antibody, synthetic and biotechnological derivatives thereof, able to recognise and bind the high affinity tyrosine kinase receptor of NGF (Nerve Growth factor), named TrkA, and act as antagonist for the binding of NGF to TrkA, and which prevents the functional activation of TrkA by NGF, and characterised by at least one CDR selected from: light chain CDRs defined by aa 46-55 of SEQ ID No 2, aa 71-77 of SEQ ID No 2 and aa 110-119 of SEQ ID No 2 and heavy chain CDRs defined by aa 176-185 of SEQ ID No. 2, aa 200-216 of SEQ ID No 2 and aa 249-262 of SEQ ID No 2. © 2017 Vossius & Partner

By Reference to a Deposit! Individually claimed monoclonal (CDR-grafted, humanized, human) antibodies that are not structurally characterized to a level that allows to understand and make them can be enabled by a deposit under the Budapest Treaty. © 2017 Vossius & Partner

Nucleic Acid Molecules! © 2017 Vossius & Partner

EP-B1 0 759 993 – Bayer BioScience GmbH 1. A DNA sequence coding for a protein having the enzymatic activity of an amylosucrase which catalyzes the synthesis of linear α-1,4 glucans from sucrose, selected from the group consisting of (a) DNA sequences coding for a protein having the amino acid sequence of the polypeptide encoded by the coding region coding for an amylosucrase from Neisseria polysaccharea as contained in the DNA insert of plasmid pNB2 (DSM 9196); (b) the DNA sequence having the nucleotide sequence of the coding region coding for an amylosucrase from Neisseria polysaccharea as contained in the DNA insert of plasmid pNB2 (DSM 9196); (c) DNA sequences hybridizing to any of the sequences of (a) or (b); (d) DNA sequences which are at least 40% identical to the DNA sequence as defined in (b); and (e) DNA sequences which are degenerate due to the genetic code in comparison to the sequences mentioned in (a), (b), (c) or (d). © 2017 Vossius & Partner

Other Examples how Deposits can help…. © 2017 Vossius & Partner

EP-B1 X XX1 XXX – Proprietor 1. An antibody or a functional part thereof, capable of recognizing and binding a specific epitope of TARGET, wherein said antibody or functional part thereof comprises an epitope-binding fragment of a monoclonal antibody obtainable from hybridoma cell line XX XXXX-XX, deposited as DSM ACCXXXX. © 2017 Vossius & Partner

... a further example based on "patent – reality"! Applicant A Applicant B Specific TARGET antibodies no sequence deposit (formally incorrect, one day to late) Prio B-I Specific α-TARGET antibodies no sequence deposit (formally correct) Prio A-I Time line Specific α-TARGET antibodies sequences! CDRs defined by SEQ IDs! Prio B-II Specific α-TARGET antibodies Sequences! CDRs defined by SEQ ID NOs (as in Prio B-II) PCT-filing Specific α-TARGET antibodies Sequences! CDRs defined by SEQ ID NOs PCT-filing Sequences turn out to be the same  "A" wins the race © 2017 Vossius & Partner

Wrap-Up: Sequence Information versus Deposits T 412/93 (Erythropoietin/AMGEN) or T 223/92 (Human-interferon/GENENTECH) Deposits not necessary to be enabled: "The need for a deposit cannot be introduced to the concept of undue burden" even if the route to success is "long and laborious" or "cumbersome"; often "earlier filings" possible when reference to "deposits" is introduced; less issues with "sequence errors" in deposits. Yet: deposits are not completely "idiot-proof" timing is relevant! despite "Budapest Treaty", the national laws play an important role the ability to obtain samples of biological material is decided upon national laws! arrangements differ immensly ("hermetic" protection in the US) T 2226/10: microorganism was no longer available at depository re-deposit necessary legal discussions! © 2017 Vossius & Partner

Prices for Patent Deposit Services Patent Deposit – Fees 2016 Accession and storage according to Rule 6.1 of the Budapest Treaty - archaea, bacteria, fungi, yeasts, plasmid DNAs, bacteriophages, plant viruses 800 € - plant cell cultures, human and animal cell cultures 1400 € Issuance of a viability statement under Rule 10.2 of the Budapest Treaty - where a viability test is requested 120 € - on the basis of the last viability test 50 € © 2017 Vossius & Partner

Remember: Quid Pro Quo Purpose of the patent system: Support innovation by granting a monopoly in exchange for an enabling technical teaching (an invention). Technical Board 3.3.08 in T 1452/06: "A basic principle of the patent system is that exclusive rights can only be granted in exchange for a full disclosure of the invention, which includes the need to indicate how to exploit the invention." AGAIN: performable is enough, performed not required! A "deposit" facilites or (in some case) even garantees "performability“and/or a “plausibel disclosure” © 2017 Vossius & Partner

“Budapest“ is alive and kicking! © 2017 Vossius & Partner

Thank you! Any questions?

For some answers ... and further reading: 6th edition was published in December 2015 by Jaenichen/Meier/McDonell/Haley/Hosoda 1st edition is published in October 2016 Editor: Jochen Bühling EPO chapter: Jürgen Meier © 2017 Vossius & Partner

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