T 1118/12 - Patient group and inherent disclosure

Key points

• "It is undisputed that the compound and the treated disorder disclosed in document D4 fall under the definitions in present claim 1, and that the patients disclosed in document D4 are immune-compromised. The question is whether they also have nasal carriage of S. aureus." "It was known from document D11 that hemodialysis patients showed a mean nasal carriage rate of 51.5% (range from 30.1% to 84.4%)." 
• "In the board's judgement, the skilled person would not have considered that the nasal carriage rates disclosed in document D11 would necessarily also apply to the later study disclosed in document D4. This is so, firstly, because document D11 also discloses that the range of carriage rates reported is large, that older studies tended to find higher carriage rates and that changes in S. aureus nasal carriage may have occurred over the years ([]). Secondly, because the skilled person would have also known that it could not be excluded that the patients of document D4 were treated topically to eliminate nasal carriage ()."
• The Board finds the claim novel over D4.
• The Board recalls that G 2/88 held that "under Article 54(2) EPC the question to be decided is what has been "made available" to the public: the question is not what may have been "inherent" in what was made available (by a prior written description, or in what has previously been used (prior use), for example)" (note that the claim is a second medical use claim).
  

EPO T 1118/12 - link

Claim 1 of auxiliary request 1A reads:
"1. A vaccine comprising a glycoconjugate of a Type 5 polysaccharide antigen of S. aureus and an immunocarrier, and a glycoconjugate of a Type 8 polysaccharide antigen of S. aureus and an immunocarrier, for use in protecting an immune-compromised individual from staphylococcal bacterial infection, wherein said immune-compromised individual has nasal carriage of S. aureus."

Reasons for the Decision

Introduction

1. The present invention relates to the use of staphylococcal glycoconjugate vaccines in preventing Staphylococcus aureus (S. aureus) infection in immune-compromised individuals who have nasal carriage of S. aureus. S. aureus causes a wide spectrum of human diseases, the most important of which is bacteremia, i.e. an invasion of the bloodstream by S. aureus. Before the priority date of the application it was considered that nasal carriage of S. aureus played a key role in the epidemiology and pathogenesis of infection (see document D11, a review article published in the year 1997, page 505, left hand column, first paragraph). Indeed, document D11 also discloses that the nasal carriage-positive patient group has a 6.3-fold higher risk of bacteremia (see page 512, left hand column, second paragraph). According to document D11 (see page 505, right hand column, first paragraph), "Approximately 20% of individuals almost always carry one type of [S. aureus] strain" (so-called "persistent carriers"). Roughly 60% of the population harbors S. aureus intermittently while 20% of the population never carries S. aureus (so-called "non-carriers")".

Auxiliary request 1A (sole request)

Novelty (Article 54 EPC)

2. Claim 1 of auxiliary request 1A is directed to a vaccine comprising glycoconjugates of capsular polysaccharide antigens of S. aureus, for use in protecting an immune-compromised individual from staphylococcal bacterial infection, "wherein said immune-compromised individual has nasal carriage of S. aureus" (see section II above for the complete wording of claim 1).

3. The examining division decided that the disclosure in document D4 anticipated the claimed subject-matter.

4. Document D4, an abstract published in April 2001, discloses the results of a clinical trial involving 1800 hemodialysis patients. In a double-blind, randomised, placebo-controlled trial, the efficacy of a bivalent S. aureus glycoconjugate vaccine that included capsular polysaccharide (CP) type 5 and 8 conjugated to a non-toxic recombinant exoprotein A from Pseudomonas aeruginosa, termed Nabi**(®) StaphVAX**(®), was evaluated. Ten months post-vaccination, 26 S. aureus bacteremias had occurred in the placebo group and 11 in the vaccinated group. This corresponded to a 57% reduction in the occurrence of bacteremia. Document D4 concludes "that StaphVAX**(®) was well tolerated, and can significantly reduce the incidence of S. aureus bacteremia in this at-risk population through approximately 10 months post-vaccination." Document D4 is silent about nasal carriage of S. aureus.

5. It is undisputed that the compound and the treated disorder disclosed in document D4 fall under the definitions in present claim 1, and that the patients disclosed in document D4 are immune-compromised. The question is whether they also have nasal carriage of S. aureus.

6. The reasoning of the examining division in holding that document D4 also disclosed the feature "wherein said immune-compromised individual has nasal carriage of S. aureus" can be summarised as follows: It was known from document D11 that hemodialysis patients showed a mean nasal carriage rate of 51.5% (range from 30.1% to 84.4%). Therefore, at least one third of the hemodialysis patients vaccinated according to document D4 carried S. aureus in their nasal cavity. Since the group of vaccinated patients was so large it was beyond reasonable doubt that at least one patient carrying S. aureus in his or her nasal cavity had been vaccinated. The examining division concluded that "thus, a patient group or individual patients defined by being immune-compromised having nasal carriage of Staphylococcal bacteria was/were inherently vaccinated in the prior art."

7. The Enlarged Board of Appeal, when considering, in its decision G 2/88 (OJ EPO 1990, 93, corr. 469), claims directed to a new use of a known compound, commented on the interpretation of Article 54(2) EPC as follows (see reasons, point 10): "Article 54(2) EPC defines the state of the art as comprising "everything made available to the public by means of a written or oral description, by use, or in any other way." (...) the question of what has been made available to the public is one of fact in each case. (...) In the case of a "written description" which is open for inspection, what is made available in particular is the information content of the written description. (...) In each such case, however, a line must be drawn between what is in fact made available, and what remains hidden or otherwise has not been made available" (emphasis added).

Furthermore, it stated in point 10.1 that "under Article 54(2) EPC the question to be decided is what has been "made available" to the public: the question is not what may have been "inherent" in what was made available (by a prior written description, or in what has previously been used (prior use), for example) (...)". [Note: However, see G 1/92]

8. For determining the information content - or disclosure - of a document, the boards have established certain principles to be observed. Thus, the information content of a document is what the skilled person derives directly and unambiguously, using common general knowledge, from the document as a whole, including features which for the skilled person are implicit in what is explicitly disclosed. In this context "implicit disclosure" means disclosure which any person skilled in the art would objectively consider as necessarily implied in the explicit content, e.g. in view of general scientific laws. In particular, the term "implicit disclosure" should not be construed to mean matter that does not belong to the content of the technical information provided by a document but may be rendered obvious on the basis of that content (see Case Law of the Boards of Appeal of the European Patent Office, 7th edition 2013, sections I.C.3.1 and I.C.3.3).

9. Given the examining division's reasoning that in view of the disclosure of document D11 "a patient group or individual patients defined by being immune-compromised having nasal carriage of Staphylococcal bacteria was/were inherently vaccinated in the prior art" (see point 6 above), the question to be addressed in the light of the observations in points 7 and 8 above is, whether or not the skilled person would have directly and unambiguously derived this disclosure from document D4 when reading it with his common general knowledge about nasal carriage rates taught in document D11.

10. The board notes that the nasal carrier rates disclosed in document D11 were determined on the basis of reports of eight different studies on nasal carriage carried out between 1975 and 1991, while the study disclosed in document D4 was carried out in the year 2000.

11. In the board's judgement, the skilled person would not have considered that the nasal carriage rates disclosed in document D11 would necessarily also apply to the later study disclosed in document D4. This is so, firstly, because document D11 also discloses that the range of carriage rates reported is large, that older studies tended to find higher carriage rates and that changes in S. aureus nasal carriage may have occurred over the years (see paragraph bridging pages 505 and 506). Secondly, because the skilled person would have also known that it could not be excluded that the patients of document D4 were treated topically to eliminate nasal carriage (see e.g. document D11, page 505, right hand column, first paragraph).

12. Hence, the board concludes from points 8 to 11 above that the skilled person would not have derived directly and unambiguously, using common general knowledge, from document D4 as a whole, the disclosure that nasal carriage-positive patients were vaccinated.

13. Lastly, also in view of the boards' established case law that the use of the same compound in the treatment of the same disease for a particular group of subjects can nevertheless represent a novel therapeutic application, provided it is carried out on a new group of subjects which has a distinct physiological or pathological status (see e.g. T 19/86, OJ EPO 1989, 24, reasons, point 8; and T 893/90, reasons, point 4.2), the board comes to the conclusion that the claimed subject-matter is novel. The patient group concerned is distinguished from the patient group of document D4 by both its physiological (nasal carriage) and pathological (higher risk of bacteremia) status.

14. In view of the observations in points 8 to 13 above the board thus concludes that the subject-matter of claims 1 to 10 is not anticipated by the disclosure of document D4.

15. Similar considerations likewise apply to document D9.

16. Therefore the board decides that auxiliary request 1A fulfils the requirements of Article 54 EPC.