“Three random basic copolymers of amino acids were tested for their effect on experimental allergic encephalomyelitis (EAE). One of these copolymers denoted as Cop 1, composed of alanine, glutamic acid, lysine and tyrosine, with a molecular weight of 23000, showed a marked suppressive effect on the disease. The intravenous administration of Cop 1 in physiological saline, as late as 5days following the challenge with the disease-inducing dose of the basic encephalitogenic protein, reduced the clinical incidence of EAE from 64 % in the control group to 22%; the histological lesions were also decreased both in prevalence and in severity. The suppressive effect on the disease attained by the synthetic copolymer is of the same order of magnitude as that previously reported for the basic encephalitogen. The effect of the copolymers appears to be specific, since neither an acidic amino acid copolymer, nor unrelated basic proteins, had any protective action. On the other hand, a second batch of Cop 1 showed activity identical to that of the first batch. The potential applicability of this non-encephalitogenic and non-immunosuppressive material is discussed.”
“2.3. Copolymers Four different random copolymers of amino acids were used in this study. Three were rich in basic amino acids, whereas the fourth one was an acidic copolymer. They were prepared from the N-carboxyanhydrides of the respective amino acids according to Katchalski and Sela [11]. 2.3.1. Copolymer 1 Cop 1 was prepared from the N-carboxyanhydrides of tyrosine [12], alanine [13], γ-benzyl glutamate [14], and ε, Ntrifluoroacetyllysine [15] (Table 1). The polymerization reaction was carried out at room temperature in anhydrous dioxane with diethylamine as initiator. The deblocking of the γcarboxyl groups of the glutamic acid was carried out with hydrogen bromide in glacial acetic acid [16], and was followed by the removal of the trifluoroacetyl groups from the lysine residues by 1 M piperidine [171] A second batch of this polymer was prepared in an identical manner. The molecular weight and amino acid composition of these polymers are listed in Table 1.”
“The average molecular weights of the polymers were determined, in a Spinco model E ultracentrifuge, from sedimentation and diffusion measurements, as described earlier [24], and by the approach to equilibrium technique of Yphantis [29].”
“Were carried out in a Beckman-Spinco automatic amino acid analyzer, Model 120-B, after hydrolysis of the samples under reduced pressure in constant boiling hydrochloric acid (6N) for 22 h [28].”
“Cop 1 is synthesised by the random polymerisation of Lalanine, L-glutamic acid, L-lysine and L-tyrosine in the ratio of 6:0:1.9:4.7:1.0 (molecular weight, 14,000 to 23,000). It was one of a series of polypeptides prepared to simulate myelin basic protein, a natural component of the myelin sheath.1-3”
“Cop 1 was first prepared at the Weizmann Institute of Science, Rehovot, Israel,1 and later by the Bio-Yeda Company in Rehovot. All batches were analyzed for their amino acid composition, molecular weight, cross-reactivity with myelin basic protein, and suppression of experimental allergic encephalomyelitis in guinea pigs. Suppression was expressed as the difference in the percentage of diseased animals between the group treated with Cop 1 and the controls. The 12 batches from the Weizmann Institute had a suppression rate ranging from 10 to 80 percent (average, 33.5 percent); the rate for 14 batches produced by Bio-Yeda ranged from 10 to 75 percent (average, 40.6 percent). In an attempt to reduce inflammatory reactions at injection sites, we used an in vitro method to evaluate cell damage (basophil degranulation) by serotonin release.18 All the batches in this study produced releases of less than 30 percent. Cop 1 was dissolved in bacteriostatic saline at a concentration of 20 mg per millilitre. Sterile single-dose vials containing 1 ml of bacteriostatic saline alone of the Cop 1 solution were stored at -20°C until they were used. Each patient received a monthly supply of 32 vials and patient compliance were monitored by a clinical assistant under the direction of the statistician responsible for the randomization of patients (see Study Design below).”
“11. … sometimes the requirement that the skilled man be uninventive is used by counsel for a patentee in an attempt to downgrade or dismiss the evidence of an expert called to say that a patent is obvious—‘my witness is more nerdlike than his’ is the general theme. I do not find this a helpful approach. It is frequently invoked and Mr Waugh Q.C. invoked it in this case in an effort to downgrade Rockwater's expert evidence on obviousness given by Professor Witz. Mr Waugh said his witness, Mr Nash, was more appropriately qualified than Professor Witz, and that the latter, because he had patents in his name, ‘was of an inventive turn of mind’. 12. I must explain why I think the attempt to approximate real people to the notional man is not helpful. It is to do with the function of expert witnesses in patent actions. Their primary function is to educate the court in the technology—they come as teachers, as makers of the mantle for the court to don. For that purpose it does not matter whether they do not approximate to the skilled man. What matters is how good they are at explaining things.” that purpose it does not matter whether they do not approximate to the skilled man. What matters is how good they are at explaining things.”
“In order to attain the high quality performance sought by the majority of the survey respondents (i.e. less than 10 % error), better approaches and methodologies for hydrolysis and amino acid analysis must be found that can routinely deliver the accuracy that is required.”
“As reflected in the Crabb paper, the core facilities at the time recognized that they were not achieving these generally accepted standards [namely, a reproducibility of typically better than 5%] for the reproducibility in amino acid analysis of peptide and protein samples.”
“What I found was that during that time people were throwing away accuracy in favour to being able to do relatively inaccurate analyses on small amounts of sample. It never made a lot of sense to me.”
“Copolymer-1 is a mixture of polypeptides composed of alanine, glutamic acid, lysine and tyrosine in a molar ratio of approximately 6:2:5:1, respectively. It is synthesised by chemically polymerising the four amino acids forming products with average molecular weights of 23,000 daltons (US Patent No. 3,849,550)”
“[0020] Copolymer-1 batch A was found to have an average molecular weight of 7-8 kDa. 2.5% of this batch had a molecular weight above 32kDa but no copolymer-1 species present in this batch had a molecular weight of over 40kDa. [0021] The other batch of copolymer-1 which was not subjected to chromatography, had an average molecular weight of 12 kDa. 2.5% of the batch had a molecular weight above 42 kDa and 5% of the total copolymer-1 species in this batch had a molecular weight over 40 kDa.”
“The RBL degranulation test is, therefore, used in order to screen out those batches of copolymer-1 which evoke substantial degranulation and thus might elicit undesirable local and/or systemic side effects.”
“As can be seen, when the % of high molecular weight species is low (< 2.5), the % release of serotonin, indicative of toxicity, is low, and vice versa.”
“[0033] Protected copolymer-1 is treated with HBr in glacial acetic acid which removes the omega benzyl protecting groups from the 5-carboxylate of the glutamate residues and cleaves the polymer to smaller polypeptides. The time needed for obtaining copolymer-1 of molecular weight 7000+2000 Da depends on the reaction temperature and the size of protected copolymer-1. At temperatures of between 20-28ºC a test reaction is performed on every batch at different time periods for example, from 10-50 hours. [0034] The results concerning the molecular weights of these small scale reactions are calculated and a curve of molecular weight against time is drawn. The time needed for obtaining molecular weight 7000+2000 Da is calculated from the curve and performed on larger scale reaction. On average, working at 26ºC the time period is 17 hours. The product is poured into excess water, filtered, washed and dried, yielding the trifluoroacetyl-copolymer-1.”
“1. A copolymer-1 fraction wherein said fraction contains less than 5% of species of copolymer-1 having a molecular weight over 40 kDa and wherein 75% of said fraction is within a molecular weight range from 2 kilodaltons to 20 kilodaltons. 2. The copolymer-1 fraction according to Claim 1, wherein said copolymer-1 has an average molecular weight of 4 to 8 kilodaltons. 3. The copolymer-1 fraction according to Claim 1, wherein said copolymer-1 has an average molecular weight of 6.25 – 8.4 kDa.”
“4. A composition for use in the treatment of multiple sclerosis, wherein said fraction contains less than 5% species of copolymer-1 having a molecular weight of over 40 kilodaltons, and 75% of said copolymer-1 in said fraction is within a molecular weight range of 2 kilodaltons to 20 kilodaltons. 5. The composition for use in the treatment of multiple sclerosis according to Claim 4, comprising a pharmaceutically effective amount of a copolymer-1 fraction, where said copolymer-1 fraction has an average molecular weight of 4 to 8 kilodaltons and a pharmaceutically acceptable carrier. 6. The composition for use in the treatment of multiple sclerosis according to Claim 4, comprising a pharmaceutically effective amount of a copolymer-1 fraction, where said copolymer-1 fraction has an average molecular weight of 6.25 to 8.4 kilodaltons and a pharmaceutically acceptable carrier.”
“7. A method of manufacturing copolymer-1 having over 75% of its molar fraction within the molecular weight range from 2 to 20 kilodaltons, comprising: reacting protected copolymer-1 with hydrobromic acid to form trifluoroacetyl copolymer-1, reacting protected copolymer-1 with hydrobromic acid to form trifluoroacetyl copolymer-1, wherein said reaction takes place for a time and at a 196. temperature predetermined by a small scale reaction, 197. treating the said trifluoroacetyl copolymer-1 with aqueous piperidine solution to form crude copolymer-1 and 198. purifying the said crude copolymer-1 to result in pure copolymer-1 having over 75% of its molar fraction within the molecular weight range 2 to 20 kilodaltons. 8. The method of Claim 7, wherein said protected copolymer-1 is reacted with hydrobromic acid for 10-50 hours at a temperature of 20-28°C. 9. The method of Claim 8 wherein said protected copolymer-1 is reacted with hydrobromic acid for about 17 hours and at a temperature of about 26°C. 10. The method of Claim 7 wherein said pure copolymer-1 has a molecular weight of 5-9 kilodaltons.” 190.Finally, two independent Swiss-style claims: “11. Use of copolymer-1 fraction, wherein said copolymer-1 has an average molecular weight of 4 to 8 kilodaltons, in manufacture of a medicament for treatment of multiple sclerosis. 12. Use of copolymer-1 fraction, wherein said copolymer-1 has an average molecular weight of 6.25 to 8.4 kilodaltons, in manufacture of a medicament for treatment of multiple sclerosis.”
“One might have thought there was nothing more to say on this topic after Kirin-Amgen Inc v Hoechst Marion Roussel Ltd[2005] RPC 9 . The judge accurately set out the position, save that he used the old language of Art.69 EPC rather than that of the EPC 2000, a Convention now in force. The new language omits ‘the terms of’ from Art.69. No one suggested the amendment changes the meaning. We set out what the judge said, but using the language of the EPC 2000: [182] The task for the court is to determine what the person skilled in the art would have understood the patentee to have been using the language of the claim to mean. The principles were summarised by Jacob LJ in Mayne Pharma Pty Ltd v Pharmacia Italia SpA[2005] EWCA Civ 137 and refined by Pumfrey J in Halliburton Energy Services Inc v Smith International (North Sea) Ltd[2005] EWHC 1623 (Pat) following their general approval by the House of Lords in Kirin-Amgen Inc v Hoechst Marion Roussel Ltd[2005] RPC 9 . An abbreviated version of them is as follows: (i) The first overarching principle is that contained in Article 69 of the European Patent Convention. (ii) Article 69 says that the extent of protection is determined by the claims. It goes on to say that the description and drawings shall be used to interpret the claims. In short the claims are to be construed in context. (iii) It follows that the claims are to be construed purposively - the inventor's purpose being ascertained from the description and drawings. (iv) It further follows that the claims must not be construed as if they stood alone - the drawings and description only being used to resolve any ambiguity. Purpose is vital to the construction of claims. (v) When ascertaining the inventor's purpose, it must be remembered that he may have several purposes depending on the level of generality of his invention. Typically, for instance, an inventor may have one, generally more than one, specific embodiment as well as a generalised concept. But there is no presumption that the patentee necessarily intended the widest possible meaning consistent with his purpose be given to the words that he used: purpose and meaning are different. (vi) Thus purpose is not the be-all and end-all. One is still at the end of the day concerned with the meaning of the language used. Hence the other extreme of the Protocol - a mere guideline - is also ruled out by Article 69 itself. It is the terms of the claims which delineate the patentee's territory. (vii) It follows that if the patentee has included what is obviously a deliberate limitation in his claims, it must have a meaning. One cannot disregard obviously intentional elements. (viii) It also follows that where a patentee has used a word or phrase which, acontextually, might have a particular meaning (narrow or wide) it does not necessarily have that meaning in context. (ix) It further follows that there is no general ‘doctrine of equivalents.’ (x) On the other hand purposive construction can lead to the conclusion that a technically trivial or minor difference between an element of a claim and the corresponding element of the alleged infringement nonetheless falls within the meaning of the element when read purposively. This is not because there is a doctrine of equivalents: it is because that is the fair way to read the claim in context. (xi) Finally purposive construction leads one to eschew the kind of meticulous verbal analysis which lawyers are too often tempted by their training to indulge.” [182] The task for the court is to determine what the person skilled in the art would have understood the patentee to have been using the language of the claim to mean. The principles were summarised by Jacob LJ in Mayne Pharma Pty Ltd v Pharmacia Italia SpA[2005] EWCA Civ 137 and refined by Pumfrey J in Halliburton Energy Services Inc v Smith International (North Sea) Ltd[2005] EWHC 1623 (Pat) following their general approval by the House of Lords in Kirin-Amgen Inc v Hoechst Marion Roussel Ltd[2005] RPC 9 . An abbreviated version of them is as follows: (i) The first overarching principle is that contained in Article 69 of the European Patent Convention. (ii) Article 69 says that the extent of protection is determined by the claims. It goes on to say that the description and drawings shall be used to interpret the claims. In short the claims are to be construed in context. (iii) It follows that the claims are to be construed purposively - the inventor's purpose being ascertained from the description and drawings. (iv) It further follows that the claims must not be construed as if they stood alone - the drawings and description only being used to resolve any ambiguity. Purpose is vital to the construction of claims. (v) When ascertaining the inventor's purpose, it must be remembered that he may have several purposes depending on the level of generality of his invention. Typically, for instance, an inventor may have one, generally more than one, specific embodiment as well as a generalised concept. But there is no presumption that the patentee necessarily intended the widest possible meaning consistent with his purpose be given to the words that he used: purpose and meaning are different. (vi) Thus purpose is not the be-all and end-all. One is still at the end of the day concerned with the meaning of the language used. Hence the other extreme of the Protocol - a mere guideline - is also ruled out by Article 69 itself. It is the terms of the claims which delineate the patentee's territory. (vii) It follows that if the patentee has included what is obviously a deliberate limitation in his claims, it must have a meaning. One cannot disregard obviously intentional elements. (viii) It also follows that where a patentee has used a word or phrase which, acontextually, might have a particular meaning (narrow or wide) it does not necessarily have that meaning in context. (ix) It further follows that there is no general ‘doctrine of equivalents.’ (x) On the other hand purposive construction can lead to the conclusion that a technically trivial or minor difference between an element of a claim and the corresponding element of the alleged infringement nonetheless falls within the meaning of the element when read purposively. This is not because there is a doctrine of equivalents: it is because that is the fair way to read the claim in context. (xi) Finally purposive construction leads one to eschew the kind of meticulous verbal analysis which lawyers are too often tempted by their training to indulge.”
“Based on the Patent alone, I understand ‘approximately’ to allow for the variability associated with the amino acid analysis technique and for the variability associated with the synthesis of the copolymer-1. I have explained above that if experimentally determined values for the composition of two samples differed by more than twice the variance [of the reproducibility of the amino acid analysis technique], then it is highly unlikely that the two samples have the same compositions. Therefore, I would understand ‘approximately 6:2:5:1’ to exclude any composition in which the molar fraction of any single amino acid differed by more than ± 10% from the calculated value of its molar fraction …”
“Compositions according to the present invention comprise a basic copolymer with a net positive electrical charge, comprising a suitable quantity of an amino acid of positive electrical charge, such as lysine or arginine, in combination with a lesser quantity of an amino acid with a negative electrical charge, such as a glutamic acid or aspartic acid, possibly with an amino acid adapted to confer immunogenic properties, such as an aromatic amino acid.”
“...that would equate, I think, to a difference of about one and a half tyrosines and that is a problem when you try and illustrate it with a monodisperse illustration. You cannot have nonintegral numbers of amino acids. In the real mixture you can and you do.”
“(1)(a) Identify the notional ‘person skilled in the art’; (b) Identify the relevant common general knowledge of that person; (2) Identify the inventive concept of the claim in question or if that cannot readily be done, construe it; (3) Identify what, if any, differences exist between the matter cited as forming part of the ‘state of the art’ and the inventive concept of the claim or the claim as construed; (4) Viewed without any knowledge of the alleged invention as claimed, do those differences constitute steps which would have been obvious to the person skilled in the art or do they require any degree of invention?”
“The question of obviousness must be considered on the facts of each case. The court must consider the weight to be attached to any particular factor in the light of all the relevant circumstances. These may include such matters as the motive to find a solution to the problem the patent addresses, the number and extent of the possible avenues of research, the effort involved in pursuing them and the expectation of success.”
“In the Court of Appeal, Jacob LJ dealt comprehensively with the question of when an invention could be considered obvious on the ground that it was obvious to try. He correctly summarised the authorities, starting with the judgment of Diplock LJ in Johns-Manville Corporation’s Patent[1967] RPC 479 , by saying that the notion of something being obvious to try was useful only in a case where there was a fair expectation of success. How much of an expectation would be needed depended on the particular facts of the case.”
“COP-1, a compound developed at the Weizman Institute in Israel, is composed of four amino acids – L-alanine, L-glutamic acid, L-lysine, and L-tyrosine - that are common in MBP. The sequence and length of the various polymers in COP-1 are random, with a molecular weight of approximately 7000. It is currently used in a therapeutic dose of 20 mg daily by subcutaneous injection.”
“Following these three provocative human studies, there was a long delay before further clinical studycould be carricd out with COP-1. In part, this was due to difficulty in expanding drug production from a research laboratory to an industrial phase, which was undertaken by TEVA Pharmaceutical Industries Ltd, the largest pharmaceutical company in Israel. It also proved difficult to develop a highly standardized preparation of COP-1 that could be employed in further clinical trials. Problems with manufacture were not solved until 1991, when it was possible to initiate further studies of COP-1 in R/R MS.”
“So what? I am not interested in that”
“…it is still difficult to predict the average degree of polymerisation and molecular weight distribution of a polyamino acid derived from a given NCA under specified conditions. It is therefore advisable to determine experimentally the average molecular weight of any new batch of polymer prepared, by the standard procedures discussed in Section IV.3.”
“What these cases show is that the principles to be applied in determining whether a claimed invention is obvious are the same regardless of the field of the invention, but that the application of those principles can vary according to the circumstances of the case, including the field of the invention. An arbitrary selection from the prior art is not inventive, regardless of the field. Nevertheless this is a problem which is more likely to arise with claims to classes of chemical compounds for the reasons explained by the Board of Appeal in Agrevo. Where it is suggested that a claimed invention is obvious as being an arbitrary selection, the key question is whether the specification ‘passes the threshold test of disclosing enough to make the invention plausible’ as Lord Hoffmann put it in Conor v Angiotech, that is to say, to make it plausible that the selection has the technical significance claimed for it.”
“I would not quarrel with Jacob LJ's comment, after consulting the Shorter Oxford English Dictionary, that the sense [‘plausibly’] conveys is that there must be some real reason for supposing that the statement is true: para. 111. The important point, however, is that the standard is not any higher than that.”
“According to the appellant’s [applicant’s] submission, in a case such as this one, where the credibility of the alleged herbicidal activity [of the claimed compounds] is at issue, the burden of proof that the presence of the alleged herbicidal activity is not credible rests on the EPO, here the Board of Appeal. This submission is clearly contrary to the legal principle that anyone who alleges a fact has the onus of proving his allegation (in this case to the standard of the balance of probabilities) by appropriate evidence. … Thus, if neither the Examining Division nor the Board of appeal is in the position to discharge this burden to the above or to any other standard, and if it is evident that the number of compounds claimed is such that it is inherently unlikely that all of them, or at least substantially all of them, will possess the promised activity, then the burden of proof of that fact, namely the possession of that activity, can indeed rest only on the shoulders of the person alleging it.”
“The Board agrees with the Respondents insofar as a technical problem set out in a patent is considered to be credibly solved by a claimed invention if there exist no reasons to assume the contrary. In such circumstances, it is normally the Opponent's burden to prove the opposite or at least provide evidence casting doubt on the alleged solution of the problem. If no such evidence is provided, the benefit of doubt is given to the Patent Proprietor. However, if the Opponent succeeds to cast reasonable doubt on the alleged effect, the burden to proof its allegations is shifted to the Patent Proprietor (Case Law of the Boards of Appeal, 6th edition 2010, chapter VI.H.5.).”
“Whether or not there was synergy demonstrated by experiments conducted after the date of the patent cannot help show obviousness or non-obviousness. Nor can the amended claim be better if only the components of the amended claim (as opposed to the unamended claim) can be shown to demonstrate synergy. The patent does not draw any such distinction and it would be quite wrong for later-acquired knowledge to be used to justify the amended claim.”
“… A patentee cannot seek to bolster the inventive nature of his monopoly by relying on a discovery which he had not made at the time of the patent. That is the position here. At the date of the Patent, Lundbeck had not found that escitalopram was more efficacious or was effective in treating more patients than citalopram. Those discoveries were not made until some time later. They are nowhere hinted at in the specification and could not have been predicted from what is described. In these circumstances I do not believe that it is legitimate for Lundbeck to rely upon them in support of the alleged invention. ”
“I add, in passing, that I do not understand the reference to ‘post-published evidence’ to include post-published evidence establishing for the first time or adding to what the potential industrial application of the patented subject-matter may be. It is surely axiomatic that whatever the standard for susceptibility to industrial application may be, the information about it must be in the patent (supplemented if necessary by the common general knowledge of the time). Otherwise you could satisfy the Art.57 requirement by just identifying a compound in the patent and finding a use for it later. That would contravene, for example, Art.5(3) of the Directive. You cannot have a patent for an invention when only years later you or someone else finds out what it is for. The same principle as applied in Johns Hopkins concerning obviousness must apply also to Art.57.”
“The molecular weights obtained using the two calibration sets within the specification range differed by, typically, not more than 20% in the low molecular weight range and by not more than 12% in the RRT [relative retention time] specification range of the peak (average molecular weight).”
“The decision as to whether there was an extension of disclosure must be made on a comparison of the two documents read through the eyes of a skilled addressee. The task of the Court is threefold: (1) To ascertain through the eyes of the skilled addressee what is disclosed, both explicitly and implicitly in the application. (2) To do the same in respect of the patent [as proposed to be amended]. (3) To compare the two disclosures and decide whether any subject matter relevant to the invention has been added whether by deletion or addition. The comparison is strict in the sense that subject matter will be added unless such matter is clearly and unambiguously disclosed in the application either explicitly or implicitly.”
“4. In Richardson-Vicks' Patent[1995] RPC 568 at 576 I summarised the rule in a single sentence: ‘I think the test of added matter is whether a skilled man would, upon looking at the amended specification, learn anything about the invention which he could not learn from the unamended specification.’ I went on to quote Aldous J in Bonzel. His formulation is helpful and has stood the test of time. 5. The reason for the rule was explained by the Enlarged Board of Appeal of the EPO in G1/93 ADVANCED SEMICONDUCTOR PRODUCTS/Limiting feature [1995] EPOR 97 at [Reasons 9]: ‘With regard to Article 123(2) EPC, the underlying idea is clearly that an applicant shall not be allowed to improve his position by adding subject-matter not disclosed in the application as filed, which would give him an unwarranted advantage and could be damaging to the legal security of third parties relying upon the content of the original application.’ 6. Mr Richard Arnold QC provided a clear articulation as to how the legal security of third parties would be affected if this were not the rule: ‘The applicant or patentee could gain an unwarranted advantage in two ways if subject-matter could be added: first, he could circumvent the "first-to-file" rule, namely that the first person to apply to patent an invention is entitled to the resulting patent; and secondly, he could gain a different monopoly to that which the originally filed subject-matter justified.’ 7. Kitchin J has recently helpfully elaborated upon the Bonzel formulation in European Central Bank v Document Security Systems[2007] EWHC 600 (Pat) ,26th March 2007 : ‘[97] A number of points emerge from this formulation which have a particular bearing on the present case and merit a little elaboration. First, it requires the court to construe both the original application and specification to determine what they disclose. For this purpose the claims form part of the disclosure (s.130(3) of the Act), though clearly not everything which falls within the scope of the claims is necessarily disclosed. [98] Second, it is the court which must carry out the exercise and it must do so through the eyes of the skilled addressee. Such a person will approach the documents with the benefit of the common general knowledge. [99] Third, the two disclosures must be compared to see whether any subject matter relevant to the invention has been added. This comparison is a strict one. Subject matter will be added unless it is clearly and unambiguously disclosed in the application as filed. [100] Fourth, it is appropriate to consider what has been disclosed both expressly and implicitly. Thus the addition of a reference to that which the skilled person would take for granted does not matter: DSM NV's Patent[2001] RPC 25 at [195]-[202]. On the other hand, it is to be emphasised that this is not an obviousness test. A patentee is not permitted to add matter by amendment which would have been obvious to the skilled person from the application. [101] Fifth, the issue is whether subject matter relevant to the invention has been added. In case G1/93, Advanced Semiconductor Products, the Enlarged Board of Appeal of the EPO stated (at paragraph [9] of its reasons) that the idea underlying Art. 123(2) is that that an applicant should not be allowed to improve his position by adding subject matter not disclosed in the application as filed, which would give him an unwarranted advantage and could be damaging to the legal security of third parties relying on the content of the original application. At paragraph [16] it explained that whether an added feature which limits the scope of protection is contrary to Art. 123(2) must be determined from all the circumstances. If it provides a technical contribution to the subject matter of the claimed invention then it would give an unwarranted advantage to the patentee. If, on the other hand, the feature merely excludes protection for part of the subject matter of the claimed invention as covered by the application as filed, the adding of such a feature cannot reasonably be considered to give any unwarranted advantage to the applicant. Nor does it adversely affect the interests of third parties. [102] Sixth, it is important to avoid hindsight. Care must be taken to consider the disclosure of the application through the eyes of a skilled person who has not seen the amended specification and consequently does not know what he is looking for. This is particularly important where the subject matter is said to be implicitly disclosed in the original specification.’ … 9. A particular, and sometimes subtle, form of extended subject matter (what our Act calls ‘additional matter’) is what goes by the jargon term ‘intermediate generalisation’. Pumfrey J described this in Palmaz's European Patents[1999] RPC 47 , 71 as follows: ‘If the specification discloses distinct sub-classes of the overall inventive concept, then it should be possible to amend down to one or other of those sub-classes, whether or not they are presented as inventively distinct in the specification before amendment. The difficulty comes when it is sought to take features which are only disclosed in a particular context and which are not disclosed as having any inventive significance and introduce them into the claim deprived of that context. This is a process sometimes called “intermediate generalisation”.’” ‘I think the test of added matter is whether a skilled man would, upon looking at the amended specification, learn anything about the invention which he could not learn from the unamended specification.’ I went on to quote Aldous J in Bonzel. His formulation is helpful and has stood the test of time. ‘With regard to Article 123(2) EPC, the underlying idea is clearly that an applicant shall not be allowed to improve his position by adding subject-matter not disclosed in the application as filed, which would give him an unwarranted advantage and could be damaging to the legal security of third parties relying upon the content of the original application.’ ‘The applicant or patentee could gain an unwarranted advantage in two ways if subject-matter could be added: first, he could circumvent the "first-to-file" rule, namely that the first person to apply to patent an invention is entitled to the resulting patent; and secondly, he could gain a different monopoly to that which the originally filed subject-matter justified.’ ‘[97] A number of points emerge from this formulation which have a particular bearing on the present case and merit a little elaboration. First, it requires the court to construe both the original application and specification to determine what they disclose. For this purpose the claims form part of the disclosure (s.130(3) of the Act), though clearly not everything which falls within the scope of the claims is necessarily disclosed. [98] Second, it is the court which must carry out the exercise and it must do so through the eyes of the skilled addressee. Such a person will approach the documents with the benefit of the common general knowledge. [99] Third, the two disclosures must be compared to see whether any subject matter relevant to the invention has been added. This comparison is a strict one. Subject matter will be added unless it is clearly and unambiguously disclosed in the application as filed. [100] Fourth, it is appropriate to consider what has been disclosed both expressly and implicitly. Thus the addition of a reference to that which the skilled person would take for granted does not matter: DSM NV's Patent[2001] RPC 25 at [195]-[202]. On the other hand, it is to be emphasised that this is not an obviousness test. A patentee is not permitted to add matter by amendment which would have been obvious to the skilled person from the application. [101] Fifth, the issue is whether subject matter relevant to the invention has been added. In case G1/93, Advanced Semiconductor Products, the Enlarged Board of Appeal of the EPO stated (at paragraph [9] of its reasons) that the idea underlying Art. 123(2) is that that an applicant should not be allowed to improve his position by adding subject matter not disclosed in the application as filed, which would give him an unwarranted advantage and could be damaging to the legal security of third parties relying on the content of the original application. At paragraph [16] it explained that whether an added feature which limits the scope of protection is contrary to Art. 123(2) must be determined from all the circumstances. If it provides a technical contribution to the subject matter of the claimed invention then it would give an unwarranted advantage to the patentee. If, on the other hand, the feature merely excludes protection for part of the subject matter of the claimed invention as covered by the application as filed, the adding of such a feature cannot reasonably be considered to give any unwarranted advantage to the applicant. Nor does it adversely affect the interests of third parties. [102] Sixth, it is important to avoid hindsight. Care must be taken to consider the disclosure of the application through the eyes of a skilled person who has not seen the amended specification and consequently does not know what he is looking for. This is particularly important where the subject matter is said to be implicitly disclosed in the original specification.’ ‘If the specification discloses distinct sub-classes of the overall inventive concept, then it should be possible to amend down to one or other of those sub-classes, whether or not they are presented as inventively distinct in the specification before amendment. The difficulty comes when it is sought to take features which are only disclosed in a particular context and which are not disclosed as having any inventive significance and introduce them into the claim deprived of that context. This is a process sometimes called “intermediate generalisation”.’”
“The present invention relates to a composition of copolymer-1 substantially free of species of copolymer-1 having a molecular weight of over 40 kilodaltons (KDa). The invention further relates to a copolymer-1 having over 75% of its molar fraction within the molecular weight range from about 2 KDa to about 20 KDa. In addition, the invention relates to a copolymer-1 having an average molecular weight of about 4 to about 8.6 KDa. Moreover, the invention relates to a pharmaceutical composition and a method for the treatment of multiple sclerosis, using the above-discussed copolymer-1.”
“The present invention relates to a composition of copolymer-1 substantially free of species of copolymer-1 having a molecular weight of over 40 kilodaltons (KDa). Preferably, the composition contains less than 5% of species of copolymer-1 having a molecular weight of 40 KDa or more. More preferably, the composition contains less than 2.5% of species of copolymer-1 having a molecular weight of 40 KDa, or more. The invention further relates to a copolymer-1 having over 75% of its molar fraction within the molecular weight range from about 2 KDa to about 20 KDa. In addition, the invention relates to a copolymer-1 having an average molecular weight of about 4 to about 8.6 KDa. In particular, the invention relates to a copolymer-1 having an average molecular weight of about 4 to about 8 KDa and a copolymer-1 having an average molecular weight of about 6.25 to about 8.4 KDa.”
“The copolymer-1 with the required molecular weight profile can be obtained either by methods known per se. Such methods include chromatography of copolymer-1 containing high molecular weight species and collecting the fractions without the undesired species or by partial acid or enzymatic hydrolysis to remove the high molecular weight species with subsequent purification by dialysis or ultrafiltration. A further method to obtain copolymer-1 with the desired molecular weight profile is by preparing the desired species while the amino acids are still protected and then obtain [sic] the correct species directly upon removing the protection.”