Life Technologies Corporation v Celsis in Vitro, Inc

Case •

[2012] APO 104

•

27 September 2012

IP AUSTRALIA

AUSTRALIAN PATENT OFFICE

Life Technologies Corporation v Celsis In Vitro, Inc. [2012] APO 104

Patent Application:                   2006240454

Title:Novel cellular compositions and methods for their preparation

Patent Applicant:  Celsis In Vitro, Inc.

Opponent:  Life Technologies Corporation

Delegate:  Dr B. Akhurst

Decision Date:  27 September 2012

Hearing Date:  4 July 2012, in Canberra

Catchwords:  PATENTS – section 59 – opposition to grant of a patent – no reasoned expert evidence in support or reply – US re-examination report relied on for grounds of novelty and inventive step – opposition unsuccessful on all grounds

Representation:  Patent applicant: Richard McCormack of Counsel, instructed by Len Mancini, Patent Attorney of Peter Maxwell & Associates, Sydney.

Opponent: No representation

IP AUSTRALIA

AUSTRALIAN PATENT OFFICE

Patent Application:                   2006240454

Title:Novel cellular compositions and methods for their preparation

Patent Applicant:  Celsis In Vitro, Inc.

Date of Decision:  27 September 2012

DECISION

The opposition fails on all grounds.  Subject to appeal, I direct the application proceed to sealing. Costs according to Schedule 8 are awarded against Life Technologies Corporation.

REASONS FOR DECISION

Background

  1. In Vitro Technologies, Inc. filed patent application 2006240454 on 30 March 2006 via the PCT, claiming priority from US basic application 11/110,879 filed on 21 April 2005.  The applicant’s change of name to Celsis In Vitro, Inc. (Celsis) was published on 21 January 2010.  After examination, the application was advertised accepted on 22 July 2010.   

  1. Life Technologies Corporation (LTC) filed a notice of opposition to grant of a patent on 22 October 2010, followed by a statement of grounds and particulars on 21 January 2011. An amendment to the statement to add a ground under section 18(1)(d) was allowed unopposed on 1 March 2012.

    Evidence

  2. Evidence in support was completed on 20 April 2011, consisting of statutory declarations by:

    ·Scott D. Miller dated 18 April 2011 (Miller#1) with exhibits SDM-1 to SDM-18

    ·Scott D. Miller dated 18 April 2011 (Miller#2) with exhibit SDM-19

  1. Evidence in answer was served on 20 December 2011, consisting of statutory declarations by:

    ·Jacob George dated 16 December 2011 (George#1) with exhibits JG-1 to JG-4

    ·Jacob George dated 16 December 2011 (George#2) with exhibits JG-5 to JG-26

  1. Evidence in reply was completed on 20 March 2012, consisting of a statutory declaration by:

    ·Scott D. Miller dated 15 March 2012 (Miller#3)

    Obvious error in the evidence

  2. In his second declaration, Celsis’ expert refers to claims 1-22.  There are only 10 claims in the opposed application.  In exhibit JG-8, a “novelty table”, Professor George has compared the disclosure of the prior art to the features of the 10 opposed claims.  Although the table lists 10 claims, it also lists 22 individual features of the claims.  This may have led to the error in the second declaration.  The second declaration does not refer to any claim individually, only to “claims 1-22” collectively.  I consider the reference to claims 1-22 to be an obvious error and consequently, where Professor George’s second declaration refers to claims 1-22, I have construed this to mean claims 1-10.

    Objection to evidence

  3. Exhibit SDM-19 to Miller#2 is a re‑examination request filed by LTC with the USPTO in respect of an equivalent US application.  Mr Miller describes the document as providing “analysis of the prior art listed in the Statement of Grounds and Particulars” (Miller#2 at [1]). 

  1. On 14 December 2011, Celsis requested the Commissioner to issue a direction that exhibit SDM‑19 to the Miller#2 declaration is inadmissible.  The Commissioner declined Celsis’ request, noting that the key consideration was the relevance of the document which is best considered at the substantive hearing. 

  1. At the hearing, Celsis again objected to the admissibility of Mr Miller’s second declaration, on the basis that the evidence was not rational and probative.  Celsis submitted that expert opinion must be comprehensible and the conclusions reached must be rationally based.  The tribunal ought not to act on an opinion, the basis for which is not explained by the witness expressing it.

  2. The Commissioner must accord each party natural justice in an opposition proceeding.  The Commissioner is not bound by the technical rules of evidence.  However, consistent with Celsis’ submissions, decisions of the Commissioner must be based on material which tends logically to establish facts relevant to the issue to be determined, or to show the probability of the occurrence of some future event the occurrence of which would be relevant.  The Commissioner may take into account any material which, as a matter of reason, has some probative value.  If it is capable of having any probative value, the weight to be attached to it is a matter for the delegate deciding the issue. (Minister for Immigration and Ethnic Affairs v. Pochi [1980] FCA 85 at [23]; 1A IPR 708 at 727 applied). The logical corollary of this reasoning is that where the evidence is of no probative value, it should be given no weight.

  3. In the present case, the issue is the weight that should be accorded the evidence, in deciding each of the grounds of opposition.  This is addressed under each ground as appropriate, in the following reasons for the decision.

    Standard of proof

  4. The onus of proof in opposition proceedings lies with the opponent, who must establish that it is clear that a valid patent cannot be granted (F.Hoffman-La Roche AG v New England Biolabs Inc [2000] FCA 283 at [29], [67]; (2001) 50 IPR 305 at 311 [29], 319 [67]; Commissioner of Patents v Sherman [2008] FCAFC 182 at [18], [22]; (2009) 79 IPR 426 at 430 [18], 432 [22]).

  1. The primary facts are to be established on the balance of probabilities, but the ultimate facts - the facts leading directly to a conclusion of a lack of novelty or a conclusion of obviousness - must be proved to the level of practical certainty (Justice Besanko in Aspirating IP Ltd v Vision Systems Ltd [2010] FCA 1061 at [35]; (2010) 88 IPR 52 at 63 [35]).

    Grounds of Opposition

  2. The grounds for opposition under section 59(b) and (c) of the Patents Act 1990 are identified in the statement of grounds and particulars as manner of manufacture, novelty, inventive step, utility, secret use, sufficiency, subsections 40(2) and 40(3) and priority date issues.

  1. The grounds based on clarity, succinctness and the validity of the priority claim are so poorly particularised that the alleged deficiencies are not clearly revealed.  LTC has not provided evidence or submissions that clarify their case under these grounds.  Therefore, these grounds will not be considered further.

    The specification and claims

  2. The application is entitled “Novel cellular compositions and methods for their preparation”.  The invention relates to cell compositions (e.g. hepatocytes) and methods for their preparation and use; methods of processing cell preparations so as to permit their repeated cryopreservation and thawing while retaining substantial viability; and cell preparations that have been repeatedly frozen and thawed (page 1). 

  1. Hepatocytes are liver cells with key roles in homeostasis (para 3).  Isolated and cultured hepatocytes have become attractive model systems for the study of liver function, and have the potential to be used in bioartificial livers or hepatocyte transplantation in order to support patients with compromised liver function (paras 4-5).

  1. A limiting factor in the development of model systems and bioartificial livers is the erratic source and limited availability of hepatocytes (para 6).  The invention permits the production and availability of hepatocyte preparations that may be repeatedly cryopreserved and thawed, without unacceptable loss of viability (para 10).  As a result of the invention, Celsis had been able to make pooled cryopreserved human hepatocyte preparations commercially available (para 10). 

  1. The specification ends with 10 claims.  Claims 1 and 10 are independent and are set out below. 

  1. Claim 1:

    1. A method of producing a desired preparation of multi-cryopreserved hepatocytes, said hepatocytes being capable of being frozen and thawed at least two times, and in which greater than 70% of the hepatocytes of said preparation are viable after the final thaw, said method comprising:

    (A) subjecting hepatocytes that have been frozen and thawed to density gradient fractionation to separate viable hepatocytes from non-viable hepatocytes,

    (B)   recovering the separated viable hepatocytes, and

    (C)  cryopreserving the recovered viable hepatocytes to thereby form said desired preparation of hepatocytes without requiring a density gradient step after thawing the hepatocytes for the second time, wherein the hepatocytes are not plated between the first and second cryopreservations, and wherein greater than 70% of the hepatocytes of said preparation are viable after the final thaw.

  2. Claim 2 further defines the density gradient fractionation solution.  Claims 3-4 define the donor species.  Claim 5 specifies that the preparation comprises pooled hepatocytes from multiple sources, and claim 6 that the sources are of the same gender, race or health state.  Claim 7 specifies that the hepatocytes in the pooled preparation provide a desired level of metabolic activity and claim 8 the nature of the activity.  Claim 9 specifies greater than 80% viability of the hepatocytes in the preparation. 

  1. Claim 10:

    10. A method of investigating in vitro drug metabolism comprising incubating hepatocytes of a multi-cryopreserved hepatocyte preparation in the presence of a xenobiotic, and determining the metabolic fate of the xenobiotic, or the affect of the xenobiotic on the hepatocytes or on an enzyme or metabolic activity thereof, wherein the hepatocytes have been frozen and thawed at least two times, and wherein greater than 70% of the hepatocytes of said preparation are viable without requiring a density gradient step after thawing the hepatocytes for the second time, wherein the hepatocytes are not plated between the first and second cryopreservations.

    Novelty

  2. A claimed invention is deprived of novelty if it has been given to the public before the priority date, either by prior use of a product or process, or by publication of information that equates to the claimed invention (Justice Bennett in Danisco A/S v Novozymes A/S (No 2) [2011] FCA 282 at [248]; (2011) 91 IPR 209 at [248]).

  1. The general test for anticipation is the reverse infringement test.  The classic formulation of this test is that given by Aicken J in Meyers Taylor Pty Ltd v Vicarr Industries Ltd [1977] HCA 19 at [20]; (1977) 137 CLR 228 at 235:

    “The basic test for anticipation or want of novelty is the same as that for infringement and generally one can properly ask oneself whether the alleged anticipation would, if the patent were valid, constitute an infringement”

  1. This test is satisfied if the alleged anticipation discloses all of the essential features of the invention as claimed (Nicaro Holdings Pty Ltd v Martin Engineering Co [1990] FCA 40 at [19]; (1990) 91 ALR 513 at 517). To meet this requirement, the prior art must contain “clear and unmistakable directions” to the claimed invention (Pfizer Overseas Pharmaceuticals v Eli Lilly and Co [2005] FCAFC 224 at [314]; (2006) 68 IPR 1 at 67 [314]).

  1. For novelty purposes, LTC relies on 18 documents to establish prior publication of the claimed method and prior use by Celsis.  In the absence of submissions, I have relied on Mr Miller’s evidence and the US re-examination request (SDM-19) to infer LTC’s case for lack of novelty.

    Prior use

  2. Subsection 7(1)(a) provides that prior art information made publicly available through doing an act may be relevant for novelty purposes.  For information to be “publically available”, the information must have been made available to at least one member of the public who, in that capacity, was free, in law and equity, to make use of it (Stanway Oyster Cylinders Pty Ltd v Marks [1996] FCA 1544 at [7]; (1996) 35 IPR 71 at 75 referring to Aldous J in PLG Research Ltd v Ardon International Ltd [1993] FSR 197 at 226). However, an allegation of prior public use must be strictly proved (Windsurfing International Inc v Petit [1984] 2 NSWLR 196; (1985) 3 IPR 449 at 489).

  1. LTC’s case for lack of novelty (and inventive step) based on prior use is that Celsis sold their Liverpool™ product before the priority date (Miller#1 at [3], Miller#3 at [2]), and that in order to prepare the product, Celsis would have carried out the method as claimed (Miller#1 at [4]).  Mr Miller’s reasoning is as follows:

    “4. The LiverpoolTM product as sold by the applicant prior to the priority date of the present application has been described in the Emig declaration [in evidence as SDM-1] as the “commercial embodiment of the present invention”.  The product sheet [in evidence as SDM-2] that was available at least before March 2005 describes the product as being “pooled cryopreserved hepatocytes”.  The pooled hepatocytes are said to either come from 5- or 10-donor populations.  Such a pooled cryopreserved hepatocyte preparation would have been made by a process involving multiple cryopreservations of hepatocytes.  The easiest way of preparing pooled hepatocytes from 5 or 10 different donors is to start from previously isolated and cryopreserved cells.  These cells must then be thawed, pooled and cryopreserved yet again.  Prior to use, the twice-cryopreserved hepatocytes must be thawed again. 

    As acknowledged by the opposed application in paragraph [0009], an end user requiring a pooled preparation of hepatocytes needs to thaw and pool hepatocytes from several different donors.  Thus, it is quite apparent from the application that it was known at the priority date that a pooled preparation of hepatocytes is prepared from previously cryopreserved hepatocytes.  The product information sheet available at least by March 2005 makes clear that the Applicant made available a cryopreserved pooled preparation, which must therefore have been frozen for a second time.  Thus, the LiverpoolTM product has the characteristics of the hepatocyte preparation required in claim 10, and produced in claim 1 of the opposed application.

    The product information sheet describes the LiverpoolTM hepatocytes as being for use in toxicity, apoptosis and metabolism studies. Claim 10 is no more than the embodiment of such studies.  There are no additional steps in claim 10 sufficient to provide novelty and/or inventive step based on the disclosure in the March 2005 product information sheet.

    As explained above, claims 1 to 9 lack novelty or inventive step in the light of the availability of the LiverPool™ product before the priority date of the present application, and in particular, the description of the product in the product information sheet.  It is apparent that a pool of cryopreserved hepatocytes requires multiple steps of cryopreservation and thawing.  The use of density gradient fractionation to enhance viability is well known in the prior art as disclosed, for example, in Ostrowska (Exhibit SDM-3).  The ability to achieve levels of viability greater than 70% is disclosed, for example, in the product information sheet and through the sale of the LiverpoolTM product.”

  1. In his third declaration, Mr Miller makes the point in similar terms:

    “Because the “invention” was described as a method for preparing a product, the product of that method, and the use of that product it is clear from this Celsis declaration [SDM-1] that the LiverpoolTM product was prepared by the claimed method.”

  2. Mr McCormack submitted that in the absence of any basis or grounding for his conclusions that LiverPool™ would have been made by the claimed method, Mr Miller’s assertions were speculative. 

  3. To establish that the opposed claims are anticipated by a prior use, LTC must establish that Celsis did in fact use the claimed method before 21 April 2005, and that the use disclosed the claimed invention to at least one member of the public who, in that capacity, was free, in law and equity, to make use of it.

  1. Exhibit SDM-1 is a declaration filed by Celsis with the US Patent and Trademark Office in respect of the US equivalent of the opposed Australian application.  Relevantly, the Celsis employee making the declaration states at [2]:

    “In 2004, IVT began selling the LiverPool™ multi-cryopreserved hepatocyte product at a premium price relative to its competitive products.  I understand that LiverPool™ is the commercial embodiment of the invention claimed in US. Patent Application No. 11/110,879.”

  1. SDM-2 is a product information statement entitled “LiverPool™ 5- and 10-Donor Pooled Cryopreserved Human Hepatocytes”.  The statement provides no additional information on how the product was prepared.

  1. At best, LTC’s evidence establishes that the LiverPool™ hepatocyte preparation may have been obtained by the claimed method before the priority date.  However, even had LTC been able to establish a prior use, the evidence does not in any way address the issue of whether such a use would have disclosed information amounting to the claimed method to at least one member of the public who was free to make use of it, with no obligation of confidentiality. 

  2. LTC has not established that the claims lack novelty in the light of a prior public use.

    Prior publication

    LiverPool™ product information statement

  3. As noted above, exhibit SDM-2 is a product information statement for LiverPool™.  The statement is undated, but Mr Miller believes that it was available before the priority date (Miller#2 at [3]).  Celsis has not disputed this.  The product information statement provides technical information in relation to LiverPool™ and its potential uses, and ordering information.  The statement provides no other indication of the method of preparation, other than describing the product as “pooled” and “cryopreserved”. 

  1. Celsis, referring to Stanway Oyster Cylinders Pty Ltd v Marks [1996] FCA 1544 at [7]; (1996) 35 IPR 71 at 75, submitted that a novelty citation must enable the notional person skilled in the art to at once perceive, understand and be able practically to apply the discovery, without the need to carry out any further experiments, in order to arrive at the product.

  2. Celsis’ expert has helpfully exhibited a “novelty table” with his evidence (JG-8).  A review of the table indicates that the LiverPool™ product information statement discloses none of the essential method steps of claim 1 and only the potential use of the product in xenobiotic studies as defined in claim 10.  Professor George is of the opinion that, at the priority date, the product information statement would not have taught the person skilled in the art the sequence of steps that make up the claimed method for preparing the multi-cryopreserved hepatocyte preparations (George#2 at 20(f)). 

  3. LTC filed no relevant evidence in reply to challenge Professor George’s interpretation of the LiverPool™ product information statement. 

  4. LTC has not established that the claims lack novelty in view of the LiverPool™ product information statement.

    Other prior art documents

  5. Other than those relating to LiverPool™, 16 prior art documents have been adduced in evidence by LTC.  The only matter in evidence in respect of these documents is contained within exhibit SDM-19, which is a re‑examination request filed by LTC with the USPTO in respect of an equivalent US application.  In his second declaration, Mr Miller states:

    “In my first declaration I referred to the re-examination that was underway in the United States.  Rather than re-cast all of the comments and analysis raised during the re‑examination I attach hereto my company’s re-examination request (marked Exhibit SDM-19) which provides analysis of the prior art listed in the Statement of Grounds and Particulars.”

  1. From Mr Miller’s first declaration and the US re-examination report, I understand that LTC’s case for novelty is that claim 10 lacks novelty in view of the following documents: 

    D1: Ostrowska et al (2000) Cell and Tissue Banking 1: 55-68

    D4: de Souza et al (1996) Cell Biology & Toxicology 12: 351-358
    D5: Shibata et al (2002) Drug Metabolism & Disposition 30(8): 892-896
    D20: Roymans et al (2004) Biochemical Pharmacology 67(3): 427-437
    D30: Chen et al (2001) Annals of Clinical & Laboratory Science 31(4): 391-397
    D31: de Graaf et al (2000) Drug Metabolism & Disposition 28(9): 1100-1106
    D32: de Kanter et al (1997) Animal Alternatives, Welfare and Ethics pages 851-6
    D33: de Kanter et al (1998) Xenobiotica 28(3): 225-234
    D34: de Sousa et al (1999) Chemico-Biological Interactions 121: 77-97
    D35: Easterbrook et al (2001) Drug Metabolism & Disposition 29(2): 141-144
    D36: Gebhardt et al (2003) Drug Metabolism Reviews 35(2&3): 145-213
    D37: Lau et al (2002) Drug Metabolism & Disposition 30(12): 1446-1464
    D38: Martignoni et al (2004) Toxicology in vitro 18: 121-128

  1. LTC’s assertions regarding lack of novelty are based on the US construction of claim 10 to encompass the use of singly cryopreserved hepatocytes (Miller#1 at para 7; SDM-19 para bridging pages 28-29). 

  1. Claim 10 defines the use, in in vitro xenobiotic studies, of a “multi-cryopreserved hepatocyte preparation”, which is further defined in terms of the method by which it is made and the final viability of the cells.  The plain meaning of the term “multi-cryopreserved” is clear, and it is reinforced by the limitation in claim 10 “wherein the hepatocytes have been frozen and thawed at least two times”.  Under Australian law, claim 10 is limited to the use of hepatocytes that have been frozen at least twice. 

  1. Celsis’ expert Professor George understands that the invention of the opposed application lies in a combination of integers and essential features, and that the sequence involved in the method for preparing the multi-cryopreserved hepatocyte preparations is an important characteristic of the method (George#2 at para 23).  He states that none of the prior art documents discloses the claimed combination of features (George#2 at paras 20(b) and 22-23 and JG-8).  In particular, he notes that the majority of the prior art is directed to the use of cells and does not deal specifically with the techniques of hepatocyte cryopreservation and thawing to obtain viable cells.  His novelty table indicates, among other things, that none of the prior art documents in evidence discloses the use of hepatocytes that have been frozen and thawed at least twice.  Although he identifies two documents, SDM-11 and -15, with the combined feature incubating the hepatocytes of a multi-cryopreserved hepatocyte preparation in the presence of a xenobiotic, a review of these documents confirms that they do not disclose the use of multi-cryopreserved cells. 

  2. LTC’s evidence in reply did not challenge Professor George’s findings in respect of the above prior art. 

  3. LTC have not established that claim 10 lacks novelty.

    Secret Use

  4. Section 18(1)(d) of the Patents Act requires that a claimed invention was not secretly used in the patent area before the priority date by, or on behalf of, or with the authority of, the patentee or nominated person or the patentee’s or nominated person’s predecessor in title to the invention. For the purposes of the Act, the “patent area” is Australia and adjacent waters and airspace.

  1. LTC has particularised 4 documents in order to establish secret prior use.  Only two are in evidence, exhibits SDM‑1 and -2 to Miller#1 relating to Celsis’ Liverpool™ product.  These documents have been discussed above.

  1. Celsis In Vitro is an American company.  LTC provided no submissions or evidence to establish any use of the claimed invention in Australia. 

  2. LTC have not established prior secret use of the claimed invention in the patent area.

    Inventive step

  3. Under the provisions of subsections 7(2) and 7(3) of the Patents Act 1990, an invention is taken to involve an inventive step when compared with the prior art base unless it would have been obvious to a person skilled in the art. “Obvious” means “very plain” (Lockwood Security Products Pty Ltd v Doric Products Pty Ltd (No 2) [2007] HCA 21 at [51]; (2007) 72 IPR 447 at 461 [51]). The invention must be obvious in the light of the common general knowledge as it existed in the patent area before the priority date, either on its own or together with information in a document, or combination of documents, that the person skilled in the art could, before the priority date of the relevant claim, be reasonably expected to have ascertained, understood and regarded as relevant and, where necessary, combined.

  1. The test for obviousness was provided by Aicken J in Wellcome Foundation Ltd v VR Laboratories (Aust) Pty Ltd [1981] HCA 12 at [45]; (1981) 148 CLR 262 at 286:

    “The test is whether the hypothetical addressee faced with the same problem would have taken as a matter of routine whatever steps might have led from the prior art to the invention, whether they be the steps of the inventor or not.”

  2. The High Court in Aktiebolaget Hässle v Alphapharm Pty Ltd (‘Alphapharm’) [2002] HCA 59 at [51]-[53]; 212 CLR 411 at [51]-[53] approved this approach.

  3. The usual approach to determining inventive step is the problem-solution approach.  Once the problem has been formulated, and the common general knowledge and the prior art base has been determined, the question of whether the claimed solution is obvious must be addressed.

    The problem

  4. The description at paras 6-8, states that a limiting factor in the development of model systems and bioartificial livers was the erratic source and limited availability of hepatocytes.  While cryopreservation methods had been developed, decreased cell viability limited the use of hepatocytes in in vitro models.  At paras 9-10 of the description, a second major problem is that liver enzyme expression varies between donors.  While this can be overcome by pooling hepatocytes from different donors to achieve a preparation with ‘average’ liver cell characteristics, pooling had been hampered by the availability of fresh tissue and the need to cryopreserve hepatocytes immediately after isolation.  At paras 9-10, the specification identifies a need in the art for processes that would enable the availability of hepatocytes for medical research and other purposes and for a stable and reproducible source of human hepatocytes. 

  1. This statement of the problem is consistent with Professor George’s evidence in his first declaration. 

    Common general knowledge in the art

    The declarants as persons skilled in the art

  2. LTC’s declarant Mr Miller describes himself as ‘Business Unit Lead IP Counsel’ of the Cell Systems Division of LTC (Miller#1 at [1]).  He does not claim to represent the person skilled in the relevant art and there is nothing in evidence to suggest this. 

  1. Celsis relies on evidence from Professor Jacob George.  Professor George’s curriculum vitae (exhibit JG-1) establishes that he is a clinician and researcher in the field of liver disease.  In April 2005 he was Director of Clinical Hepatology in the Dept of Gastroenterology and Hepatology at Westmead Hospital, a position he had held since 2000, and Associate-Professor of Medicine, University of Sydney.  Prior to this he had extensive research experience in gastroenterology/hepatology dating back to 1988, and had published widely.  I conclude that Professor George is, and was at the priority date of the application, a person skilled in the art relevant to the opposed application.

    The common general knowledge

  2. LTC has particularised 42 documents to establish the common general knowledge in the art.  None are in evidence.  LTC’s particulars explicitly claim, and Professor George’s evidence confirms, that the following were common general knowledge in the art:

    (i) the culturing of hepatocytes required certain conditions including media;

    (ii) the freezing and thawing (cryopreservation) of hepatocytes required certain conditions if the viability of the hepatocytes were to be preserved;

    (iii)the freezing and thawing of hepatocytes caused certain physiological effects which needed to be mitigated if the viability of the hepatocytes were to be preserved.

  1. Professor George’s first declaration, which was made without knowledge of the specification (para 18), provides further evidence of the common general knowledge in the art in Australia.  There were various methods for human cell isolation, for cryopreservation and for recovery of the cells after cryopreservation ((para 24(6)(a)).  The main disadvantage of using cryopreserved human hepatocytes was that their viability after re-thawing was reduced compared to fresh hepatocytes, and that thawed cells loose some functionality (paras 24(6)(e)-(f), 24(8)). 

  2. Cryopreserved hepatocytes could be used for studies of drug metabolising enzyme activities and throughput screening (para 24(10)(a)).  Human drug metabolism varied markedly between individuals and the importance of obtaining data from preparations from different individuals was known (para 24(10)(c)).  If several human samples were available at one time for cell isolation, hepatocytes from several individuals could be pooled and stored to obtain a composite picture (para 24(10)(d)-(e)).  However, obtaining human hepatocytes was difficult and they were a scarce resource (para 24(10)(b)).  Alternatively, and more likely, the skilled addressee would have pooled several cryopreserved hepatocyte preparations at the time the vials were unthawed (para 24(10)(f)). 

    Prior art base

  3. In order to establish lack of inventive step, LTC particularised 38 prior art documents.  As noted above, only 18 of these are in evidence.  Two relate to the availability and use of the LiverPool™ product before the priority date.  The remaining documents are journal articles. 

    Matters of routine

  4. The test for inventive step is would the person skilled in the art have taken the necessary steps to arrive at the claimed invention, not could they have taken those steps.  The question is a practical one, rather than a theoretical question of what might have been done. 

  1. Mr Miller states that ‘the art is replete with references that render the opposed application obvious’ (Miller#1 at para 9).  Mr McCormack asserted that Mr Miller’s was a cavalier approach, and that his statements consisted of assertions which were unsupported by any chain of reasoning or other intellectual basis that could be considered rational and probative.  As noted above, the nature of evidence may affect the weight it is accorded in the opposition proceedings before the Commissioner.

  1. I will first consider inventive step in view of the disclosure of the LiverPool™ product and its product information statement, and then the other prior art documents in evidence, in order to determine whether it would have been a matter of routine to proceed from this prior art information to the claimed invention.

    LiverPool™ and its product information statement

  2. From Mr Miller’s evidence, it is clear that LTC wish to press inventive step in light of the LiverPool™ product and its associated product information statement.  Given that the field of hepatology is a global one, and the information statement directly relates to the product, on the balance of probabilities, I consider that the person skilled in the art in Australia could reasonably be expected to have ascertained, understood and regarded the information as relevant, and to have combined it.

  1. Mr Miller’s relevant evidence is reproduced above at [28]. From this, I understand LTC’s case for inventive step, to be as follows:

    (i)The LiverPool™ product and its product information statement was available before the priority date. 

    (ii)The ability to achieve levels of viability greater than 70% is disclosed, for example, in the product information sheet and through the sale of the LiverpoolTM product.

    (iii)The person skilled in the art would expect pooled hepatocytes to be prepared from thawed cells, which would have to be cryopreserved for a second time to arrive at the commercial product, and thawed by the user prior to use. 

    (iv)The product information sheet teaches the suitability of the LiverpoolTM hepatocytes in toxicity, apoptosis and metabolism studies. 

    (v)The use of density gradient fractionation to enhance viability is well known in the prior art as disclosed, for example, in Ostrowska (D1).

  1. Mr Miller’s statement at (iii) above, is at odds with Professor George’s evidence summarised above at [64], which suggests that the person skilled in the art would understand a cryopreserved pooled hepatocyte preparation to have been prepared from several fresh samples available at the one time, which would be pooled then stored (eg. cryopreserved).  Regarding (v), although density gradient fractionation may be well known in the art, Mr Miller provides no evidence that the person skilled in the art would, as a matter of routine, have applied it according the present claims.  Nor does Mr Miller provide any evidence that the person skilled in the art would exclude from the method a plating step between the first and second cryopreservations and understand that a further density gradient step was unnecessary after the final thaw. 

  1. As indicated above, Celsis’ expert, who is a person skilled in the art, understands the invention to lie in a combination of integers and essential features, and that the sequence involved in the method for preparing the multi-cryopreserved hepatocyte preparations is an important characteristic of the method (George#2 at para 23).  Professor George concludes that the inventors have exercised inventive faculties to come up with the claimed invention.  In his opinion, it would not have been a matter of routine to proceed to the claimed method, in particular because the person skilled in the art would consider the claimed method counter-intuitive and contraindicated.  (George#2 at paras 38-40 and 22)

  1. Mr Miller’s third declaration does not include any evidence that could refute or qualify Professor George’s evidence. 

  2. LTC have not established that the claimed invention was obvious in the light of the information provided by the LiverPool™ product and its product information statement in combination.

    Published prior art

  3. In 271 pages, the US re-examination request provides information as to the obviousness of the claims in light of 4 of the following documents taken alone, and 120 different combinations of these documents:

    D1: Ostrowska et al (2000) Cell and Tissue Banking 1: 55-68

    D4: de Souza et al (1996) Cell Biology & Toxicology 12: 351-358
    D5: Shibata et al (2002) Drug Metabolism & Disposition 30(8): 892-896
    D20: Roymans et al (2004) Biochemical Pharmacology 67(3): 427-437
    D30: Chen et al (2001) Annals of Clinical & Laboratory Science 31(4): 391-397
    D31: de Graaf et al (2000) Drug Metabolism & Disposition 28(9): 1100-1106
    D32: de Kanter et al (1997) Animal Alternatives, Welfare and Ethics pages 851-6
    D33: de Kanter et al (1998) Xenobiotica 28(3): 225-234
    D34: de Sousa et al (1999) Chemico-Biological Interactions 121: 77-97
    D35: Easterbrook et al (2001) Drug Metabolism & Disposition 29(2): 141-144
    D36: Gebhardt et al (2003) Drug Metabolism Reviews 35(2&3): 145-213
    D37: Lau et al (2002) Drug Metabolism & Disposition 30(12): 1446-1464
    D38: Martignoni et al (2004) Toxicology in vitro 18: 121-128

  4. It is not apparent that the US re-examination request has been compiled by the person skilled in the art.  Although it may incorporate information gained from such a person, there is no clear indication of this.  For this reason, and because it has been prepared in the context of US law, I have construed the re-examination request as submissions on the law in that jurisdiction, rather than evidence from the person skilled in the art. 

    Combinations of documents

  5. For all of the different combinations of documents raised in the re-examination request, I have no evidence before me to establish that, before the priority date, the person skilled in the art could reasonably be expected to have ascertained, understood and regarded the documents as relevant, and to have combined them, as required by section 7(3) of the Australian Patents Act.  Therefore, I will not further consider the combinations in this opposition. 

    Individual documents

  6. The four documents individually relied on by LTC to establish lack of inventive step are:

    D4: de Souza et al (1996) Cell Biology & Toxicology 12: 351-358
    D20: Roymans et al (2004) Biochemical Pharmacology 67(3): 427-437
    D34: de Sousa et al (1999) Chemico-Biological Interactions 121: 77-97
    D36: Gebhardt et al (2003) Drug Metabolism Reviews 35(2&3): 145-213

  7. In the context of inventive step, neither party has addressed the question of whether these documents would have been ascertained, understood and regarded as relevant.  Given the problem, and that the above documents all relate to the use of hepatocytes in in vitro studies, prima facie they would have been ascertained, understood and regarded as relevant. 

  1. Each of the above documents discloses the preparation of singly-cryopreserved hepatocytes and their use in in vitro studies.  Would it have been a matter of routine to proceed to the claimed invention? 

  2. As indicated above, from his reading and understanding of the prior art, Professor George considers that the inventors have exercised their inventive faculties to come up with a new and much improved method, involving cryopreserving recovered hepatocytes, without requiring a density gradient step after thawing the hepatocytes a second time.  In his opinion, at the priority date, the claimed means of achieving multi-cryopreserved hepatocyte preparations was not a matter which the person skilled in the art would have taken as a matter of routine, to arrive at the new and improved hepatocyte preparation.  He considers that the claimed invention is of a character which a skilled addressee at the priority date “would have regarded as contraindicated, in the sense of being a solution which they would have arrived at, either singularly or as a member of a team, as a matter of routine” (George#2 at 39-40). 

  1. Mr Miller’s third declaration does not provide anything that could refute or qualify Professor George’s evidence. 

  2. LTC have not established that the claimed invention was obvious in the light of any one of the documents listed above at [75].

    Manner of Manufacture

  3. Section 18(1)(a) requires that an invention must be a manner of manufacture within the meaning of section 6 of the Statute of Monopolies.  Whether an invention is a manner of manufacture is assessed by asking whether the claimed invention lacks the necessary quality of inventiveness on the face of the specification (NV Philips Gloeilampenfabrieken v Mirabella International Pty Ltd [1995] HCA 15 at [9]; (1995) 183 CLR 655 at 655).

  1. LTC’s particulars under this ground are, relevantly, that:

    ·one or more of claims 1-10 defines a known goal by mere desiderata; and

    ·the claims reflect nothing more than a use of known techniques and materials for which the known properties of the materials make them suitable. 

  2. LTC made no submissions to support this ground.

  1. On this point, Celsis submitted that on the face of the specification, it is not apparent that the claimed method was known.  Celsis pointed to Professor George’s evidence which describes the claimed invention as “… a significant step forward for medical research as concerned with a new means for achieving multi-cryopreserved hepatocyte preparations” (George #2 at [60]). 

  2. LTC have not established that the invention is not a manner of manufacture.

    Utility

  3. A claim will lack utility if it includes subject matter that will not produce the desired result (H Lundbeck A/S v Alphapharm Pty Ltd [2009] FCAFC 70 at [81], [217]; (2009) 81 IPR 228 at [81], [217]; Ranbaxy Australia Pty Ltd v Warner-Lambert Co LLC [2008] FCAFC 82 at [141]; (2008) 77 IPR 449 at 479 [141])

  1. Under this ground, LTC’s particulars state that the claimed invention does not achieve the purpose of a claim and/or does not provide the result alleged in the description to be obtained.  Specifically,

    “… the alleged invention lacks utility, since all that it provides is a method of removing non-viable hepatocytes after an initial freeze/thaw cycle using known density gradient fractionation methods.  There is no guarantee that greater than 70% of the hepatocytes will be viable following a second or more freeze/thaw cycles.”

  1. As noted by Celsis, LTC has adduced no evidence that would establish that the claimed method will not produce the desired result. 

  2. LTC has not established that the opposed claims lack utility.

    Section 40(2)(a): Full description

  3. Section 40(2)(a) requires that a complete specification must describe the invention fully, including the best method known to the applicant of performing the invention.  The “invention” in section 40 is “the embodiment which is described, and around which the claims are drawn” Kimberly-Clark Australia Pty Ltd v Arico Trading International Pty Ltd [2001] HCA 8 at [19], [21]; (2001) 207 CLR 1 at 14 [19], 15 [21].

  1. The High Court in Kimberly-Clark [2001] HCA 8 at [25]; (2001) 207 CLR 1 at 17 [25] provided the test for full description:

    “The question is, will the disclosure enable the addressee of the specification to produce something within each claim without new inventions or additions or prolonged study of matters presenting initial difficulty?”

  1. LTC’s particulars under this ground seem to be directed to the European ground of clear and complete disclosure rather than full description.  However, in his first declaration, Mr Miller provides LTC’s case under full description:

    “… I believe that the specification of the opposed application is insufficient and a person of ordinary skill in the art would fail to fulfil the promise of the alleged invention.  The specification does not fully describe the alleged invention, including the best method of performing the alleged invention known to the applicant.  For example, claims 1 and 10 require that the hepatocytes are separated via a density gradient step after the initial freeze/thaw; however, these claims also state that a further density gradient step is not required “after thawing the hepatocytes for the second time [and] wherein the hepatocytes are not plated between the first and second cryopreservations, and wherein greater than 70% of the hepatocytes of said preparation are viable after the final thaw.”  There is absolutely no disclosure in the application as filed related to “cryopreserving the recovered viable hepatocytes to thereby form said desired preparation of hepatocytes without requiring a density gradient step after thawing the hepatocytes for the second time, wherein the hepatocytes are not plated between the first and second cryopreservations, and wherein greater than 70% of the hepatocytes of said preparation are viable after the final thaw.”  Nowhere in the specification of the opposed application are these aspects disclosed or described.  Therefore, the invention is not described fully.” (Emphasis in original)

  1. Mr McCormack submitted that Mr Miller has provided no foundation for his statements, which in the absence of supporting evidence were not rational or probative.  To refute Mr Miller’s statements, they refer to Professor George’s statement the claimed invention is fully described including the best method of performance (George #2 at [66]). 

  1. In effect, LTC’s argument is that the specification does not refer to method steps that are explicitly excluded from the claimed method or described as not required.  A specification cannot be considered insufficient because it does not describe or exemplify unnecessary method steps.  This conclusion is consistent with the High Court’s statement in Kimberly-Clark (supra) at [25]:

    “It is not necessary that [the applicant] should describe in his specification the manner in which the invention is to be performed, with that wealth of detail with which the specification of the manufacturer of something is usually put before the workman who is engaged to manufacture it.”

  2. The specification describes a method of producing a multi‑cryopreserved hepatocyte preparation that does not include plating between the first and second cryopreservations or a density gradient step after the second thaw (see paras 32-50 and Examples 1 and 2).  Example 3 at Table IV indicates that pooled multi-cryopreserved hepatocytes retain a post-thaw viability of greater than 70%.  The requirement for a full description is therefore satisfied.

  1. LTC have not established that the opposed application lacks a full description.

    Section 40(3): Fair basis

  2. Section 40(3) requires that the claim or claims in a patent specification must be fairly based on the matter described in the specification.

  1. As the test for fair basis, the High Court in Lockwood Security Products Pty Ltd v Doric Products Pty Ltd [2004] HCA 58 at [69]; (2004) 217 CLR 274 at 300 [69] approved the words of Gummow J in Rehm Pty Ltd v Websters Security Systems (International) Pty Ltd (1988) 81 ALR 79 at 95:

    “… the question is whether there is a real and reasonably clear disclosure in the body of the specification of what is then claimed, so that the alleged invention as claimed is broadly, that is to say in a general sense, described in the body of the specification.”

100. The High Court in Kimberly-Clark v Arico [2001] HCA 8 at [15]; (2001) 207 CLR 1 at 12 [15] and Lockwood v Doric [2004] HCA 58 at [57]; (2004) 217 CLR 274 at 300 [57], approved the principle provided by Barwick CJ in Olin Corporation v Super Cartridge Co Pty Ltd [1977] HCA 23 at [6]; (1994) 180 CLR 236 at 240:

“The question whether the claim is fairly based is not to be resolved, in my opinion, by considering whether a monopoly in the product would be an undue reward for the disclosure.  Rather, the question is a narrow one, namely whether the claim to the product … as expressed, travels beyond the matter disclosed in the specification”. 

101. LTC’s particulars under this ground seem to be directed to the European ground of lack of support, rather than fair basis.  Nevertheless, the following particulars appear relevant to fair basis:

“… the claims are of the type that define a known goal by reference to a desired result.  The claims include within their scope all possible solutions to a known and obvious goal, and consequently, represent nothing more than mere desiderata.”

102. LTC have provided no submissions to establish their case under this ground.

103. Celsis submitted that the objection has not been made out, since the claimed invention is broadly described in the body of the specification.  Professor George had no difficulty in concluding that the invention defined in the claims was the subject of a real and reasonably clear disclosure (George#2 at [67]).

104. LTC have not established that the claims lack fair basis.

Conclusion

105. Life Technologies Corporation has failed to establish its grounds of opposition.  Unless the Commissioner is served with a notice of appeal within 28 days of the date of this decision, I direct the application proceed to sealing. 

106. As noted above, the onus of proof in opposition proceedings lies with the opponent.  In this opposition, LTC has not made any real effort to establish its grounds of opposition or to make its case under Australian law.  While matter in the US re-examination request may have been relevant to the opposition in Australia, the actions of the opponent did not assist in providing a clear indication of the case to be answered in Australia.  In the absence of reasoned expert evidence and submissions explaining how the material in evidence applies to the case under Australian law, the opposition was poorly prosecuted.  The actions of the opponent in this case are inconsistent with a serious opposition.

Costs

107. It is normal in actions before the Commissioner for costs to follow the event.  I can see no reason to depart from the normal award of costs.  Life Technologies Corporation opposition has been unsuccessful on all grounds.  I therefore award costs in accordance with Schedule 8 against Life Technologies Corporation.

Barbara Akhurst
Delegate of the Commissioner of Patents

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