BAXTER INTERNATIONAL INC.

[1992] APO 11

official notice

decision of a delegate of the commissioner of patents

Application        :       No. 27137/88 in the name of BAXTER INTERNATIONAL INC.

Title:       Microcrystalline matrix for administration of beneficial agent.

Action            :       Examiner's objections.

Decision           :       Issued           

Certain claims lack novelty and clarity.

patents act 1990

decision of a delegate of the commissioner of patents

Re:Patent Application No. 27137/88 by BAXTER INTERNATIONAL INC. Examiner's Objections

background

Application No. 27137/88 by Baxter International Inc. entitled "Microcrystalline matrix for administration of beneficial agent" was filed as an international application on 8 November 1988.  Following a request for examination, the examiner's first report issued on 12 September 1990.  Several sets of amendments to the specification were proposed by the applicant but the examiner maintained objections to novelty and to clarity.

A stalemate situation was reached and the attorney Peter Maxwell of Peter Maxwell and Associates requested that the matter be heard under section 216 of the Patents Act 1990. The attorney later advised that he did not wish to appear at the hearing and merely wanted a decision on the written record under the provisions of Regulation 22.23.

THE SPECIFICATION

In the specification as lodged the invention related to a method of passing medical solution through a conduit wherein the improvement involved passing that medical solution across a solid mass of beneficial agent positioned within said conduit.  In original claims 1-15 the beneficial agent comprised a material selected from the group consisting of "citrate and mannitol".  The beneficial agent in claims 18 to 21 comprised a material selected from the group consisting of "non-toxic sugars, sugar alcohols and salts".  The remaining claims (16 and 17) were directed to a microcrystalline tablet comprising either a mixture of sodium citrate and citric acid or mannitol, proportioned for positioning in the flow conduit.

As a result of the examiner's objections the applicant deleted claims 18 to 21 and proposed 3 sets of amended claims.  The claims under consideration are those as amended by the fourth statement of amendments filed on 7 August 1991.  The independent proposed claims 1, 7, 13, 16 and 17 read as follows:

1.A method of passing medical solution through a conduit, the improvement comprising: passing said medical solution across a solid mass of microcrystalline beneficial agent positioned within

said conduit, said microcrystalline beneficial agent comprising a material selected from the group consisting of citrate and mannitol in a substantially anhydrous form.

7.The method of passing medical solution through a conduit, the improvement comprising: passing said medical solution across a solid mass of microcrystalline beneficial agent positioned within said conduit, said microcrystalline beneficial agent containing at least 30 weight percent of citrate or mannitol, said mass of microcrystalline beneficial agent being shaped and proportioned whereby a controlled amount of said microcrystalline beneficial agent dissolves into passing solution at a substantially uniform rate of dissolution.

13.The method of passing medical solution through a conduit, the improvement comprising: passing said medical solution across a solid mass of microcrystalline beneficial agent positioned within said conduit, said microcrystalline beneficial agent comprising a material selected from the group consisting of citrate and mannitol in a substantially anhydrous form, along with an added beneficial ingredient other than said citrate and mannitol.

16.A microcrystalline tablet proportioned for positioning in a flow conduit for dissolving in a stream of a medical solution passing through said flow conduit, said tablet comprising a mixture of sodium citrate and citric acid.

17.A microcrystalline tablet proportioned for positioning in a flow conduit for dissolving in a stream of a medical solution passing through said flow conduit, said tablet comprising mannitol.

PRIOR ART

In the cited prior art document, US Patent 4552555, the invention relates to a system for intravenous delivery of a beneficial agent.  The beneficial agent is defined as "any substance that produces a therapeutic or a beneficial result, such as a drug, a carbohydrate, an electrolyte and/or the like" (column 4 lines 47-49).  The specification further states that "Exemplary pharmaceutically acceptable forms include solid, crystalline, microcrystalline, particle, pellet, granule, powder, tablet, spraydried, lypohilized, compressed forms that undergo disintegration and dissolution in the presence of an intravenous fluid ..." (column 4 lines 29-34).

In claim 10 of the citation there is the disclosure "a beneficial intravenously administrable drug presented in a therapeutically effective amount for producing a beneficial effect in tablet form that undergoes dissolution" in the presence of an intravenous fluid.

In claim 11 of the citation there is disclosed "a beneficial intravenously administrable drug present in a therapeautically effective amount for producing a beneficial effect in a lyophilized form ...".  Furthermore column 6 lines 15-18 makes the added disclosure "Delivery from such system can be controlled, for example, by the rate of dissolution as governed by particle size of agent and the solubility of the agent in the fluid".  The citation does not specifically mention citrate or mannitol as examples of the beneficial agents.

SUBMISSIONS

In essence the applicant argued during the course of examination that US Patent 4552555 did not disclose the dissolution in a conduit of a beneficial agent comprising a solid mass of a microcrystalline material consisting of citrate or mannitol in a substantially anhydrous form.

The examiner however was of the opinion that US Patent No. 4552555 disclosed all the features of the invention apart from restricting the beneficial agent to citrate or mannitol.  However these compounds fell within the definition of "beneficial agents" and unless they clearly had "unexpected properties" that difference did not add novelty to the invention defined in the claims.

This was the state of affairs when a hearing was set down to resolve the impasse.  Mr Maxwell was unable to attend the hearing but instead made a submission in writing.  In that submission he presented arguments which may be summarised as follows:

1.The solid mass of a microcrystalline beneficial agent comprising citrate or mannitol was not disclosed in US Patent No. 4552555.  Because this is an essential feature of the invention claims 1-17 (which all contain this feature) are not prior published by the citation.

2.The difference between the claimed invention and the disclosure in US Patent No. 4552555 concerning the beneficial agent cannot be considered a workshop variation or a mechanical or chemical equivalent and therefore the claims are novel in the light of the citation.

3.As a fall back position at pages 9-10 he submitted "the invention is a selection from US Patent No. 4552555.  The selection is in respect of the substantial advantage gained by using citrate or mannitol in the specific physical form claimed when dissolving the solid mass into a solution for intravenous administration.  Thus by ensuring that the beneficial agent is microcrystalline substantially anhydrous citrate or mannitol favourable solubility properties may be achieved.  Since US Patent No. 4552555 does not discuss citrate or mannitol these properties could not have been predicted for the particular substances citrate and mannitol from the US patent.  Thus the selection of microcrystalline, substantially anhydrous citrate or mannitol has the characteristic of being unexpected".

4.With respect to the clarity objection directed to claims 16 and 17 Mr Maxwell has responded by suggesting at pages 4-5 that the introductory portion of each claim be amended to read:

"A microcrystalline tablet shaped and proportioned whereby a controlled amount of a microcrystalline beneficial agent dissolves into passing solution at a substantially uniform rate of dissolution, which may be positioned in a flow conduit for dissolving in a stream of medical solution passing through said flow conduit ...".

DECISION

With respect to argument (1) I point out that the examiner's report did not contain any unresolved prior publication objections.  There is no disagreement on this point between the examiner and the attorney.

I now turn my attention to argument (2) relating to novelty.  In his submission on page 8 it is the attorney's contention that the citation does not disclose the physical form or the water content of the beneficial agent (ephedrine sulphate) unlike the present invention where the beneficial agent (citrate or mannitol) is solid microcrystalline and substantially anhydrous.  Furthermore (he goes on to say) when collecting blood from a donor there is a problem in the prior art that the bag (which contains a measured amount of anticoagulant for that particular bag) has to be completely filled so that it contains the appropriate concentration of anticoagulant.  In the present invention when a solid mass of microcrystalline citrate is used as the anticoagulant it dissolves into the blood at a constant rate which ensures that the appropriate concentration of anticoagulant is present in the blood even if the blood bag is not completely filled.

Similarly solid microcrystalline substantially anhydrous mannitol (on its own or together with another drug) can be administered to a patient in a controlled manner by dissolution into a passing parenteral solution.

In my opinion the citation US Patent No. 4552555 does make disclosures which indicate that the beneficial agent can be solid microcrystalline and substantially anhydrous.  Claim 10 of the US patent discloses a tablet form of the beneficial agent which is the solid form used in claims 16 and 17 of the present invention.  Furthermore in claim 11 of the US patent the beneficial agent is in a lyophilized form.  Also column 4 lines 28-36 of the US patent clearly discloses microcrystalline as a feature.  As far as I am concerned the only feature which was not disclosed in the citation is a specific mention of citrate or mannitol as particular examples of beneficial agents.  In view of the fact that the present invention does not involve the discovery of new chemical or pharmaceutical properties of the citrate and mannitol (i.e. the citrate and mannitol are used in the invention because of their known beneficial properties), and in the light of the disclosure at column 6 lines 15-19 of US Patent No. 4552555 (quoted at page 3 above), I find it difficult to see how the present invention is novel in the light of the disclosure in the US citation.

In my opinion the feature which distinguishes the present invention from the one disclosed in US Patent No. 4552555 is the discovery that the solid mass of microcrystalline citrate or mannitol can be shaped and proportioned so that it then dissolves into the passing solution at a substantially uniform rate of dissolution as described at page 3 lines 5-9.  The attorney has argued that the citrate and mannitol have unexpected favourable solubility properties.  However I believe that the solubility is only favourable when the solid mass of microcrystalline citrate or mannitol has been shaped and proportioned.  In other words the geometry of the microcrystalline solid mass is important and it is that geometry which gives a uniform rate of dissolution which is the distinguishing feature of this invention.  It is my contention that only those claims which contain the feature - shaped and proportioned so that the mass of microcrystalline beneficial agent then dissolves into the passing solution at a substantially uniform rate of dissolution - define a novel invention.

I therefore find that claims 1, 2, 3, 5, 6, 13 and 14 which do not contain this feature are not novel.  I find that claims 4, 7, 8, 9, 10, 11, 12 and 15 which do contain this feature are novel.

With respect to claims 16 and 17 I agree with the examiner that there is a valid clarity objection.  The words "shaped and proportioned" only have a clear meaning if they relate to the process in which the tablets are used.  If the attorney amends the introductory portion of the claims as he has suggested (See argument 4 above), in my opinion, he will overcome the clarity objection.  Furthermore because the claims would now also contain the features  "shaped and proportioned ..." and "... at a substantially uniform rate of dissolution" the objection to novelty will also be overcome.

I will now consider argument (3) in which the attorney has submitted that citrate and mannitol have unexpected favourable solubility properties which would entitle it to be a selection of US Patent No. 4552555.

I.G. Farbenindustrie A.G.'s Patents, 47 RPC 289 laid down the following criteria for a valid "selection" patent.

(a)the selection must be based on some substantial advantage gained or some substantial disadvantage avoided;

(b)the whole of the selected members must possess the advantage in question;

(c)the selection must be in respect of a quality which may fairly be said to be peculiar to the selected group.

I believe that the present application cannot satisfy criterion (c).  Mr Maxwell suggested that the favourable quality is the solubility property of citrate and mannitol.  However it appears that other beneficial agents have solubilities which would enable them to behave in a similar manner and this would seem to be supported by the passage in the U.S. citation in column 6 lines 15-18 which makes it clear that the solubility of the beneficial agent "can be controlled".

Consequently I do not believe that the solubility of the citrate and mannitol is a quality which is peculiar to these two beneficial agents when compared to other beneficial agents.  In my opinion the solubility is not a quality which can be used to support the argument for a selection patent.

CONCLUSION

I have found that claims 1, 2, 3, 5, 6, 13 and 14 are not novel in the light of disclosures in US Patent No. 455255.  These claims also do not fulfill the requirements for a selection patent.  Claims 16 and 17 also lack clarity.  However I believe the application does contain patentable subject matter.  The time for acceptance of the application expires on 12 June 1992.  I will therefore give the applicant the opportunity to propose amendments to my satisfaction within the time remaining for acceptance.

(JANET WERNER)
Delegate of the Commissioner of Patents

Patent attorneys for the applicant:  Peter Maxwell & Associates,
   Sydney

Peter Maxwell and Associates
PO Box 2309
North Parramatta
NSW  2151

RE:Patent application no. 27137/88 in the name of BAXTER INTERNATIONAL INC.  Examiner's objections.

Your ref:89 1 077.

Gentlemen,

Please find attached a copy of the Decision of a Delegate of the Commissioner in the above matter.

Senior Clerk, Patents.