Pharmacosmos Holding A/S v American Regent, Inc - [2020] APO 36

IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Pharmacosmos Holding A/S v American Regent, Inc. [2020] APO 36

Patent Application: 2016205002

Title:Methods and compositions for administration of iron

Patent Applicant:                   American Regent, Inc.
Opponent:  Pharmacosmos Holding A/S
Delegate:  Dr A. Lim
Decision Date:  29 July 2020
Hearing Date:  03 June 2020, via video conference

Catchwords: PATENTS – opposition under section 104 – allowability under subsections 102(1) and 102(2) considered – “as a result of the amendments” – whether as a result of the amendment, “the skilled person is being presented with any new information about the invention which is not directly and unambiguously apparent from the original disclosure” – whether as a result of the amendments, the specification does not provide a clear enough and complete enough disclosure – whether as a result of the amendments, the claims are not supported, not clear or not succinct – amendments allowable – cost awarded against the opponent

Representation: Patent attorney for the applicant: Houlihan² Pty Ltd by written submissions only
Patent attorney for the opponent: Griffith Hack by written submissions and video conference

IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Patent Application: 2016205002

Title:Methods and compositions for administration of iron

Patent Applicant: American Regent, Inc.
Date of Decision: 29 July 2020
DECISION
The opposition is unsuccessful on all grounds.
I allow the amendments filed on 24 April 2019.
Cost according to Schedule 8 are awarded against Pharmacosmos Holding A/S.
REASONS FOR DECISION
1. Background

Patent application number 2016205002 (the application) was filed on 18 July 2016 as a divisional application from 2013206429 (the parent application) which is in turn a divisional from 2007205167. The application claims an earliest priority date of 06 January 2006 (the priority date). The application was originally filed in the name of Luitpold Pharmaceuticals, Inc. On 04 February 2019, the application was assigned to American Regent, Inc. (American) who are now the applicant.
The application was examined and advertised accepted by the Commissioner on 01 February 2018. The grant of a patent was subsequently opposed under section 59 of the Patents Act 1990 (the Act) by Pharmacosmos Holding A/S (Pharmacosmos). The opposition to the grant of a patent is still proceeding.
American filed amendments on 24 April 2019 and leave to amend was advertised on 13 June 2019. Pharmacosmos served a notice of opposition to the allowance of the amendments on 13 August 2019 and filed a statement of grounds and particulars (SGP) on 13 September 2019. It is the opposition to the allowance of amendments (s104 opposition) only that is the subject of this decision.
Accompanying the SGP, Pharmacosmos also filed a declaration by Dr Vito Ferro, dated 29 January 2019, and six other documents. On 02 October 2019, the Commissioner issued a direction that any documents accompanying the SGP will be treated as evidence in support of the section 104 opposition. Pharmacosmos filed no additional evidence in support. American filed no evidence in answer.
2. The opposition
The grounds of opposition pressed in written submissions and at the hearing were that the proposed amendments are not allowable under:
·subsection 102(1) because, as a result of the amendments, the specification would claim or disclose matter extending beyond that disclosed in the complete specification as filed; and
·paragraph 102(2)(b) because, as a result of the amendments the proposed amendments, the specification would fail to comply with paragraph 40(2)(a) and subsection 40(3) in that
othere would be non-compliance with the disclosure requirements for the specification;
othe claims would not be supported; and
othe claims would be unclear.
3. The applicable law
The application was filed on 18 July 2016. As a consequence, the amendments of the Act brought about by the Intellectual Property Laws Amendment (Raising the Bar) Act 2012 apply to the present application. This includes amendment to section 40 and section 102 of the Act.[1]
[1] Schedule 1, items 55(1)(d) and 55(9)(d) of the Raising the Bar Act.
Subsection 104(1) states that the applicant is entitled to request amendments:
(1) An applicant for a patent or a patentee, may, subject to this Act, and subject to and in accordance with the regulations, ask the Commissioner for leave to amend the relevant patent request or complete specification, or any other filed document, for any purpose including either or both of the following:
(a) removing a lawful ground of objection to the request or specification, whether that objection is raised in the course of an examination or re-examination or otherwise;
(b) correcting a clerical error or an obvious mistake.
Subsection 104(4) provides for opposition to amendment:
(4) The Minister or any other person may, subject to and in accordance with the regulations, oppose allowing an amendment.
Subsection 104(5) sets out the criteria for allowability of amendment:
(5) The Commissioner must not allow an amendment that is not allowable under section 102.
Section 102 governs the allowability of amendments:
(1) An amendment of a complete specification is not allowable if, as a result of the amendment, the specification would claim or disclose matter that extends beyond that disclosed in the following documents taken together:
(a) the complete specification as filed;
(b) other prescribed documents (if any).
(2) An amendment of a complete specification is not allowable after the relevant time if, as a result of the amendment:
(a) a claim of the specification would not in substance fall within the scope of the claims of the specification before amendment; or
(b) the specification would not comply with subsection 40(2), (3) or (3A).
The documents that have been prescribed for the purposes of paragraph 102(1)(b) are set out in regulation 10.2A. In the present case, the only “other prescribed document’ is the abstract that was filed with the complete specification.
As set out in subsection 102(2A), the “relevant time” is after the specification has been accepted. Therefore, as the present application has been accepted when the amendments were requested, the requirements of subsection 102(2) apply.
The relevant parts of subsections 40(2) and 40(3) for the purposes of this decision are:
(2) A complete specification must:
(a) disclose the invention in a manner which is clear enough and complete enough for the invention to be performed by a person skilled in the relevant art;
(3) The claim or claims must be clear and succinct and supported by matter disclosed in the specification.
Both subsections 102(1) and 102(2) require consideration of consequences that follow as a result of the amendment. The expression “as a result of the amendments” was a feature of section 102 before the recent changes brought about by Raising the Bar Act and has been considered on many occasions. In RGC Mineral Sands Ltd v Wimmera Industrial Minerals Pty Ltd Carr and Sundberg JJ discussed section 102(1) as it stood at the that time:
“That subsection requires one first to identify precisely what is the amendment. In this case that is done by identifying the difference between the specification as accepted (and as it stood at the hearing of the motion at first instance) on the one hand and, on the other hand, as the specification would read if amended in the manner sought. … The subsection focuses on the amendment proposed and it must be that amendment which has the result of pushing the claimed matter over the line defined by the expression [‘matter that extends beyond that disclosed’] … The key point to keep in mind is, as counsel for the respondent contended (in our view correctly), that the words ‘as a result of the amendment’ are not to be confused with the expression ‘after the amendment’.”[2]
[2] [1998] FCA 1358; 42 IPR 353 at page 360.
Therefore, the general approach to a consideration of subsection 102(1) is:
·firstly, identify the changes to the description and the claims by reason of the amendment proposed—what matter would be claimed or disclosed as a result of the amendment; and
·then, determine whether, as a result of the amendment, the specification would claim or disclose additional matter.
It is key to the approach to consider matter that is claimed or disclosed as a result of the amendment, and not matter claimed after the amendment.
Pre-existing defects in the specification are not relevant to the consideration of the allowability of amendments under section 102, as noted by Bennett J in Apotex. [3] Such deficiencies may be relevant to the opposition under section 59.
[3] [2009] FCA 1019 at [28]; 83 IPR 42.
The general approach to a consideration of paragraph 102(2)(b) is similar. Bennett J stated in Apotex Pty Ltd v Les Laboratoires Servier (No 2) (Apotex):
“… s 102(2)(b) requires:
1. Identification of the precise amendment sought by identifying the difference between the specification as it stood immediately before the amendment and the specification as proposed to be amended; and
2. Determination whether, as a result of the amendment, the specification would not comply with s 40(2) or s 40(3)”[4]
[4] [2009] FCA 1019 at [34]; 83 IPR 42.
The Explanatory Memorandum, Intellectual Property Laws Amendment (Raising the Bar) Bill 2011 makes it clear that section 102 as amended is intended to prevent the addition of new matter to the description:
“The item introduces a provision preventing amendment of a complete patent specification after filing to add new matter that would go beyond the disclosure contained in the specification at its filing date. An applicant would not be able to amend the specification to add any material that the hypothetical skilled person could not directly derive by reading the information in the specification as filed.”[5]
[5] Item 29, page 61.
Recently, subsection 102(1) was considered in Commonwealth Scientific and Industrial Research Organisation v BASF Plant Science GmbH (CSIRO).[6] Beach J considered a number of decisions of the United Kingdom courts and saw no good reason not to follow them to the extent of applying analogous concepts to the present form of s 102(1).[7] Among the decisions is Richardson-Vicks Inc’s Patent, where Jacob J stated:
“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.” [8]
[6] [2020] FCA 328.
[7] CSIRO at [214].
[8] [1995] RPC 568 at [576].
Referring to European Central Bank v Document Security Systems Inc,[9] Beach J noted that he should compare the specification as proposed to be amended with its unamended form in order to:
“… see whether any subject matter relevant to the invention has been added. And this comparison is a strict one. Subject matter will be added ‘unless it is clearly and unambiguously disclosed in the application as filed.’ Moreover, it is appropriate to consider what has been disclosed both explicitly and implicitly.”[10]
[9] [2007] EWHC 600 (Pat).
[10] CSIRO at [203].
What is clearly and unambiguously disclosed does not extend to matter that would have been obvious to the reader of the specification:
“what I am considering and applying is not an obviousness test. As Kitchen J described it, a patentee ‘is not permitted to add matter by amendment which would have been obvious to the skilled person from the application.’”[11]
[11] ibid.
Beach J also noted that the concept of intermediate generalisation as described in the United Kingdom is an established aspect of “added matter”.[12] His Honour considered a number of United Kingdom decisions which explained the concept of intermediate generalisation.[13] Among the decisions is Nokia Corporation v IPCom GmbH & Co KG (No. 3), where Kitchen LJ explained:
“Turning to intermediate generalisation, this occurs when a feature is taken from a specific embodiment, stripped of its context and then introduced into the claim in circumstances where it would not be apparent to the skilled person that it has any general applicability to the invention.
Particular care must be taken when a claim is restricted to some but not all of the features of a preferred embodiment, as the TBA explained in decision T 0025/03 at point 3.3 … ‘if a claim is restricted to a preferred embodiment, it is normally not admissible under Article 123(2) EPC to extract isolated features from a set of features which have originally been disclosed in combination for that embodiment. Such kind of amendment would only be justified in the absence of any clearly recognisable functional or structural relationship among said features…’ So also, in decision T 0284/94 the TBA explained … that a careful examination is necessary to establish whether the incorporation into a claim of isolated technical features, having a literal basis of disclosure but in a specific technical context, results in a combination of technical features which is clearly derivable from the application as filed, and the technical function of which contributes to the solution of a recognisable problem. Moreover, it must be clear beyond doubt that the subject matter of the amended claim provides a complete solution to a technical problem unambiguously recognisable from the application.
It follows that it is not permissible to introduce into a claim a feature taken from a specific embodiment unless the skilled person would understand that the other features of the embodiment are not necessary to carry out the claimed invention. Put another way, it must be apparent to the skilled person that the selected feature is generally applicable to the claimed invention absent the other features of that embodiment.
Ultimately the key question is once again whether the amendment presents the skilled person with new information about the invention which is not directly and unambiguously apparent from the original disclosure. If it does then the amendment is not permissible.”[14]
[12] CSIRO at [205].
[13] CSIRO at [206]-[210].
[14] [2013] RPC 5 at [56]-[60].
Beach J stated:
“In summary, an amendment utilising a feature may amount to added subject matter, such that it is not relevantly disclosed, even where there is a literal reference to such a feature in the specification as filed. An example of where this may occur is where by reason of the amendment, a feature that was not suggested to be significant is, for the first time, suggested to have a technical significance. Such a suggestion of technical significance might arise where a feature is taken from a specific embodiment, and introduced into a claim in a manner that is stripped from relevant context provided by that embodiment. To avoid a conclusion of added subject matter, the skilled person must have appreciated from the complete specification as filed that the selected feature was more generally applicable. This may involve asking whether the skilled person is being presented with any new information about the invention which is not directly and unambiguously apparent from the original disclosure. Further, even if a feature was suggested to be technically significant, an impermissible intermediate generalisation may take place if by the amendment the feature is used in a manner significantly different from its original context.”[15]
and
“Further, there may be an impermissible intermediate generalisation where a new combination of features is sought to be created by the proposed amendment which was not apparent in the application as filed. …”[16]
[15] CSIRO at [211].
[16] CSIRO at [213].
However, Beach J noted:
“…, what constitutes an impermissible addition of subject matter by way of an ‘intermediate generalisation’ is to be distinguished from an amendment that claims a sub-class of an inventive concept, whether or not it is presented as inventively distinct in the specification as filed. This is consistent also with established practice in relation to patent claiming, where a patent will routinely include cascading claims directed to progressively narrower characterisations of the disclosed invention. A patent applicant is not limited to a single patent claim, directed to a preferred embodiment.”[17]
[17] CSIRO at [212].
In regard to the law in Australia, Beach J stated that:
“..., the concept of intermediate generalisation as discussed in the UK authorities applies to s 102(1) in its construction and application.”[18]
[18] CSIRO at [218].
4. The specification
The specification relates generally to the treatment of iron-related conditions with iron carbohydrate complexes.[19] The specification describes that parenteral iron therapy is known to treat iron-related disorders but currently available parenteral iron drugs have health risks and dosage limitations associated with their use.[20] Serious and life-threatening reactions are stated to occur most frequently with iron dextran, but also occur with other parenteral iron products. The high incidences of anaphylactoid-type reactions (that is, dyspnea, wheezing, chest pain, hypotension, urticaria, angioedema) is believed to be caused by the formation of antibodies to the dextran moiety.[21] While the incidences of anaphylactoid-type reactions is markedly lower with the use of other parenteral iron products, such as iron sucrose and iron gluconate, the physiochemical properties of these products lead to dosage limitations.[22]
[19] The specification at [0002].
[20] The specification at [0003].
[21] The specification at [0004] – [0005].
[22] The specification at [0005].
The specification states that the invention is directed to the use of iron carbohydrate complexes that can be administered parenterally at relatively high single unit dosages to provide a safe and efficient means for delivery of a total dose of iron in fewer sessions over the course of therapeutic treatment.[23] Under the heading “SUMMARY OF THE INVENTION”, the specification teaches methods of treating a disorder characterised by iron deficiency or dysfunctional iron metabolism through the administration of at least about 0.6 grams of elemental iron via single unit dosage of an iron carbohydrate complex to a subject that is in need of such therapy.[24] The summary then describes that in various embodiments, the single dosage unit of elemental iron is between at least about 0.6 grams and 2.5 grams.[25] In the detailed description of the invention, the specification describes administration of iron carbohydrate complexes in single unit dosages of at least 0.6 grams to about at least 2.5 grams of elemental iron.[26]
[23] The specification at [0008], [0026].
[24] The specification at [0009].
[25] The specification at [0011]; paragraph [0011] falls under the heading “SUMMARY OF THE INVENTION”.
[26] The specification at [0034].
The specification exemplifies an iron carboxymaltose, a polynuclear iron (III)-hydroxide 4 (R)-(poly-(1→4)-O-α-glucopyranosyl)-oxy-2(R),3(S),5(R),6-tetrahydroxy-hexanoate, “VIT-45”, as the preferred iron carbohydrate complex.[27] Another preferred iron carbohydrate complex is a polyglucose sorbitol carboxymethyl ether-coated non-stoichiometric magnetite, “ferumoxytol”.[28] However, the specification lists examples of other suitable iron carbohydrate complexes which are described to be used with the invention including iron polyisomaltose complex.[29]
[27] The specification at [0065] – [0073], [0101] – [0133], Figures 1 and 2.
[28] The specification at [0062], [0074] – [0076].
[29] The specification at [0015], [0059].
Iron polyisomaltose complex is mentioned at paragraph [0015] in the section under the heading “SUMMARY OF THE INVENTION” and at paragraph [0059] in the detailed description of the invention under the heading “Iron Carbohydrate Complex” which provides examples of iron carbohydrate complexes which are described to be used with the invention.

After describing the iron carbohydrate complexes which can be used with the invention, the specification states:
“Applicants have discovered that certain characteristics of iron carbohydrate complexes make them amenable to administration at dosages far higher than contemplated by current administration protocols. Preferably, iron carbohydrate complexes for use in the methods described herein are those which have one or more of the following characteristics: a nearly neutral pH (eg. about 5 to about 7); physiological osmolarity; stable carbohydrate component; an iron core size no greater than about 9 nm; mean diameter particle size no greater than about 35 nm, preferably about 25 nm to about 30 nm; slow and competitive delivery of the complexed iron to endogenous iron binding sites; serum half-life of over about 7 hours; low toxicity; non-immunogenic carbohydrate component; no cross reactivity with anti-dextran antibodies; and/or low risk of anaphylactoid/hypersensitivity reactions.”[30] (Emphasis added)
[30] The specification at [0060].
I consider that the skilled person would interpret the plain meaning of the term “one or more of the following characteristics”, used in the specification and quoted above, to be stating that one, or a combination of two or more, of the described characteristics provides a solution to the technical problem of administering the iron carbohydrate complexes at higher dosages. Since iron polyisomaltose complex is mentioned in the preceding paragraph in the specification, I consider that the skilled person would recognise that iron polyisomaltose complex has characteristics that is amenable to administration at dosages far higher than contemplated by current administration protocols.
As no amendments have been made to the description during the prosecution of the present application, what I have just discussed about the specification relates to the specification as originally filed.
5. The nature of the amendments
Amendments have been proposed for only the claims, and a marked-up version of the proposed amendments relevant for this opposition is reproduced in Annex A of this decision.
6. Are the amendments allowable under subsection 102(1)?
The opponent submitted:
“There is no description in the specification of the AU’022 application as filed that identifies an iron polyisomaltose complex with the following combination of features:
(i) a substantially non-immunogenic carbohydrate;
(ii) substantially no cross-reactivity with anti-dextran antibodies; and
(iii) an iron core size of at least about 1 nm and no greater than 9 nm;
that can be administered in a single dosage unit of at least 1.1 grams of elemental iron and where the subject does not experience significant adverse reaction to the single dosage unit administration. While there is literal reference to each of these features, this combination of features is not disclosed in the specification of the AU’022 application as filed.”[31]
and
“In particular, the feature of substantially no cross-reactivity with anti-dextran antibodies would not have been something that a skilled person would have considered to be combinable with an iron polyisomaltose complex, a term used interchangeably with iron dextran (seen in paragraph [0059] of the specification),⁴⁷ and sharing the same chemical structure⁴⁸ as iron dextran.”[32]
[31] The opponent’s written submissions, dated 20 May 2020, at [9.5].
[32] The opponent’s written submissions, dated 20 May 2020, at [9.6].
In reply to the opponent’s submission, the applicant submitted:
“Turning to paragraph 9.5, the Opponent sets out features of the amended claim that are allegedly beyond the scope of the disclosure of the as-filed specification. The Applicant notes that each of the listed features (i), (ii) and (iii) were present in claims 1, 2 and 15 of the as-filed claims. Further, each of the claims were multiply dependent and ultimately dependent on claim 1. The change of minimum dosage to ‘at least 1.1 grams’ was clearly within the scope of as-filed claim 1. Accordingly, the Opponent’s allegation has no merit.”[33]
[33] The applicant’s written submissions, dated 27 May 2020, at [47]. As-filed claim 1 recites an iron carbohydrate complex in a single dose unit of at least about 0.6 grams of elemental iron, lists a group of iron carbohydrate complex which consists of iron polyisomaltose complex, and recites the iron carbohydrate complex has a substantially non-immunogenic carbohydrate component. As-filed claim 2 is dependent on as-filed claim 1 recites the iron carbohydrate complex has substantially no cross reactivity with anti-dextran antibodies. As-filed claim 15 is appended on any one of as-filed claims 1-14 and recites the mean iron core size is at least about 1 nm but no greater than 9 nm, or the mean size of a particle of the iron carbohydrate complex is no greater than about 35 nm.
Having previously considered the legal principles, a key question I am to ask here is whether, as a result of the amendment, the skilled person is being presented with any new information about the invention which is not directly and unambiguously apparent from the original disclosure. Another way of putting this question is to ask whether, as a result of the amendment, additional matter would be claimed or disclosed which the hypothetical skilled person could not directly derive by reading the information in the specification as filed. If it does, then the amendment is not permissible.
Proposed claim 1
A marked-up copy of the proposed amendments to claim 1 is reproduced below:
A method of treating a disease, disorder, or condition characterized by iron deficiency or dysfunctional iron metabolism resulting in reduced bioavailability of dietary iron, comprising:
administering to a subject in need thereof an iron carbohydrate complex in a
single dosage unit of at least ~~0.7~~1.1 grams of elemental iron;
wherein:
the iron carbohydrate complex:
-is an iron polyisomaltose complex;
~~the iron carbohydrate complex~~ has a substantially non-immunogenic
carbohydrate component; ~~and~~
has substantially no cross reactivity with anti-dextran antibodies;
comprises an iron core having a mean iron core size of at least about 1 nm but
no greater than about 9 nm;
and wherein the subject does not experience a significant adverse reaction to the
single dosage unit administration.
What matter is claimed as a result of the proposed amendment to claim 1?
Before the proposed amendments, claim 1 was directed to a method of treatment comprising administering an iron polyisomaltose complex in a single dosage unit of at least 0.7 grams of elemental iron. The iron polyisomaltose complex was recited to have a substantially non-immunogenic carbohydrate component and the subject was recited not to experience a significant adverse reaction to the single dosage unit administration.
After the proposed amendments, the method of claim 1 comprises administering an iron polyisomaltose complex in a single dosage unit of at least 1.1 grams of elemental iron, and the additional features defined for claim 1 are the iron polyisomaltose complex has substantially no cross reactivity with anti-dextran antibodies and the mean iron core size is recited within a specific range. A dosage unit of “at least 1.1 grams” falls within the scope of a dosage unit of “at least 0.7 grams”. The other features of the proposed amendments for claim 1 further define the non-immunogenic nature and the iron core of the iron carbohydrate complex.
Therefore, as a result of the amendments, new proposed claim 1 now claims matter that had already been part of claim 1 before the amendment. This matter is also part of the original disclosure and as-filed claims. I note that no amendments have been proposed to the description.
As I previously discussed, the specification as originally filed discloses administration to a subject of single unit dosages of elemental iron between at least about 0.6 grams and 2.5 grams. A single dosage unit of elemental iron of at least about 1.1 grams is explicitly mentioned at paragraph [0011] of the specification. The specification also discloses the characteristics of iron carbohydrate complexes that make them amenable to administration at high dosages—this is in paragraph [0060] quoted above. I previously concluded that the skilled person would understand that iron carbohydrate complexes with one, or a combination of two or more, of the characteristics described in paragraph [0060] were generally applicable to the invention. These characteristics include a level of the non-immunogenic nature of the carbohydrate component, non-cross reactivity with anti-dextran antibodies and an iron core size of no greater than 9 nm—characteristics that form part of the proposed amendments for claim 1. I also discussed that in the context in which iron polyisomaltose is mentioned in the specification, the skilled person would interpret that iron polyisomaltose is one example of such an iron carbohydrate complex.
Does the matter claimed, as a result of the amendments, in proposed claim 1 result in the specification disclosing or claiming matter which extends beyond that disclosed in the complete specification as filed?
I consider the combination of features claimed in proposed claim 1, as a result of amendments, is directly and unambiguously apparent to the skilled person from the original disclosure. There is no new information about the invention that the skilled person is being presented with as a result of the amendments. If there are any deficiencies with regard to the claims, as submitted by the opponent, these deficiencies do not arise as a result of the amendments proposed to the claims.
Proposed claim 2
A marked-up copy of the proposed amendments to claim 2 is reproduced below:
A method of claim 1, wherein the ~~iron carbohydrate complex has substantially no cross reactivity with anti-dextran antibodies.~~single dosage unit of elemental iron is:
i) at least 1.1 grams to about at least 2.5 grams; or
ii) at least about 1.1 grams to at least 1.5 grams; or
iii) about 1.5 grams; or
iv) at least 1.5 grams; or
v) up to about 2.0 grams.
The opponent submitted that the specification as filed does not disclose the ranges of options (i), (ii) or (v).[34] The opponent also submitted that as a result of the amendments options (i) and (ii) are unclear.[35]
[34] The opponent’s written submissions, dated 20 May 2020, at [9.9].
[35] The opponent’s written submissions, dated 20 May 2020, at [8.17].
Since the interpretation of terms in proposed claim 2 is important to an understanding of what matter is claimed as a result of the amendments, I will now consider the meaning of several terms.
“at least”
One definition the Macquarie dictionary provides for “at least” is at the least or lowest estimate.[36] I interpret the plain meaning of the term to define a lowest limit or minimum gram quantity of elemental iron. For example, “at least 1.5 grams” in option (iv) of proposed claim 2 means a minimum of 1.5 grams and no less than 1.5 grams.
[36] Macquarie dictionary online.
“about”
The term “about” is often used to qualify numerical quantities to indicate that small variations from the specified value are envisaged.[37] The extent of the variance depends on what the skilled person would understand is intended. I have previously discussed that the summary of the invention describes methods of treatments through the administration of at least about 0.6 grams of elemental iron via single unit dosage of an iron carbohydrate complex to a subject, and the single dosage unit of elemental iron is between at least about 0.6 grams and 2.5 grams in various embodiments.[38]
[37] Patent Manual of Practice and Procedure at 2.11.2.3.8.
[38] The specification at [0009], [0011].
The specification at paragraph [0011] states:
“In various embodiments, the single dosage unit of elemental iron is between at least about 0.6 grams and 2.5 grams. In some embodiments, the single dosage unit of elemental iron is at least about 0.7 grams; at least about 0.8 grams; at least about 0.9 grams; at least about 1.0 grams; at least about 1.1 grams; at least about 1.2 grams; at least about 1.3 grams; at least about 1.4 grams; at least about 1.5 grams; at least about 1.6 grams; at least about 1.7 grams; at least about 1.8 grams; at least about 1.9 grams; at least about 2.0 grams; at least about 2.1 grams: at least about 2.2 grams: at least about 2.3 grams; at least about 2.4 grams; or at least about 2.5 grams.”
Given that paragraph [0011] recites single dosage unit of elemental iron in 0.1 gram increments, I consider the skilled person would understand that “about” allows a ±0.1 gram variation in the gram quantity of elemental iron. I also consider that the skilled person would understand from the first sentence of paragraph [0011] that in one embodiment, the single dosage unit of elemental iron falls within a range of 0.6 ±0.1 grams to 2.5 ±0.1 grams of elemental iron.
“at least 1.1 grams to about at least 2.5 grams”, “at least about 1.1 grams to at least 1.5 grams”
Regarding proposed claim 2, the opponent submitted:
“It appears from the Applicant’s covering letter to the proposed amendments dated 24 April 2019⁴³ that options (i) and (ii) are intended to be ranges,⁴⁴ but in fact these options recite two lower limits (“… at least … to at least …”) and no upper limit. It is not clear whether options (i) and (ii) are intended to refer to a closed range or whether they are intended to provide a range for the lower limit of elemental iron to be administered.
Option (ii) is also unclear as it recites a range of lower limits that, at least on one view, extends beyond the scope of claim 1. …. New claim 2 option (ii) refers to a lower limit for the single dosage unit as ‘at least about 1.1 grams’. The inclusion of the term “about” in option (ii) of claim 2, but not in option (i), implies that the single dosage unit may be below 1.1 grams. …”[39]
[39] The opponent’s submissions, dated 20 May 2020, at [8.18] – [8.19].
Do the terms in options (i) and (ii) of proposed claim 2 define a range with a minimum and maximum gram quantity of elemental iron, or do they define two lower limits?
I have previously interpreted the term “at least” to define a lowest limit or minimum gram quantity of elemental iron, and the term “about” to qualify numerical quantities to allow a ±0.1 gram variation of in the quantity of elemental iron.
The recitation of the second “at least” in options (i) and (ii) of proposed claim 2, is awkward and raises the question of what the second “at least” means. However, I consider the term “to” in “… at least… to… at least…” has some work to do. I interpret the plain meaning of “to” indicates a range with a minimum and a maximum gram quantity of elemental iron. As previously discussed, various parts of the specification describe embodiments of the invention which administer single unit dosages between about 0.6 grams and 2.5 grams of elemental iron.[40] I consider the skilled person, reading the specification as a whole, would interpret proposed claim 2, options (i) and (ii) to recite a range with a minimum and maximum gram quantity of elemental iron. Additionally, I note that the applicant has chosen to use five different options to define the single dosage unit of elemental iron in proposed claim 2. I interpret options (i) and (ii) to define the dosage of elemental iron to be within a range while option (iv) defines the lowest limit of the dosage of elemental iron.
[40] The specification at [0011] and [0034].
Proposed claim 2 is dependent on claim 1 and therefore incorporates all the features of claim 1. The opponent’s question of whether or not the term “about” in option (ii) includes a single dosage unit below 1.1 grams elemental iron can be resolved in the context of this claim dependency. I consider a skilled person would interpret option (ii) to define the single dosage unit of elemental iron to have a minimum of 1.1 grams with a variation in the first decimal place above 1.1 grams and not below 1.1 grams. I consider the upper limit of the range of claim 2, option (ii) to be a maximum of 1.5 grams.
It is unfortunate that the applicant has chosen to not use more decisive language to express the single dosage unit of elemental iron of options (i) and (ii). While I have interpreted the meaning of the terms of proposed claim 2 in line with the approach of a person skilled in the art, the applicant’s language has made this process a lot more complex than it needed to be. It would be beneficial for the applicant, who still has the opportunity to amend the claim, to use more definitive language.
“Up to about 2.0 grams”
I consider the terms “up to” define a maximum gram quantity of elemental iron. As claim 2 is dependent on claim 1, I interpret option (v) of proposed claim 2 to define the single dosage unit of elemental iron having a range with a minimum of 1.1 grams and a maximum of 2.0 grams ± 0.1 grams.
What matter is claimed as a result of the amendments?
As a result of the proposed amendments, new claim 2 now claims various single dosage units of elemental iron that had already been within the scope of claim 1 before the amendment. The various single dosage units of elemental iron fall within the scope of “at least 0.7 grams”. These dosages were also disclosed in the specification as filed. The specification clearly discloses embodiments of the invention which administer single dosage units of elemental iron administered that are defined (a) within a range of 0.6 ±0.1 grams to 2.5 ±0.1 grams, and (b) with a lowest limit of 0.6 ±0.1 grams of elemental iron. Therefore, options (i) to (v) explicitly claim gram quantities of elemental iron that is directly and unambiguously apparent to the skilled person from the original disclosure.
Does the matter claimed, as a result of the amendments, in proposed claim 2 result in the specification disclosing or claiming matter which extends beyond that disclosed in the complete specification as filed?
I now ask whether, as a result of the amendment to claim 2, the skilled person is being presented with new information about the invention which is not directly and unambiguously apparent from the original disclosure. From the discussion above, the answer is clearly no. If there are any deficiencies with regard to the claims, as submitted by the opponent, these deficiencies do not arise as a result of the amendments proposed to the claims.
Conclusion regarding allowability of amendments under subsection 102(1)
I conclude the specification would not, as a result of the amendments, claim or disclose matter extending beyond that disclosed in the complete specification as filed considered together with the abstract. Consequently, the proposed amendments are allowable under subsection 102(1) and the opponent is unsuccessful in relation to this ground.
7. Are the amendments allowable under paragraph 102(2)(b) with regard to subsection 40(2)?
The opponents submitted:
“The specification of the AU’002 application provides a laundry list of iron carbohydrate complexes that could be used in the methods disclosed, … The only limitation in the disclosure of the specification of the AU’002 application on this potential universe of complexes is the circular requirement that they must have the properties the inventors ‘discovered’ were desirable, including (at [0060]): ‘non-immunogenic carbohydrate component; no cross-reactivity with anti-dextran antibodies; and/or low risk of anaphylactoid / hypersensitivity reactions.
However, the specification of the AU’002 application does not explain what chemical structures would manifest those desired properties—particularly regarding immunogenicity. To the contrary, the specification of the AU’002 application teaches that the claimed iron polyisomaltose complexes are the same as iron dextrans (at [0059]), which the specification says must be avoided in view of potential hypersensitivity reactions (for example, anaphylaxis) believed to be caused by anti-dextran antibodies.
As a result of the amendment, claim 1 now requires that an iron polyisomaltose complex be administered in an amount of at least 1.1 gram of elemental iron and with substantially no cross-reactivity with anti-dextran antibodies, substantially no immunogenicity and substantially no adverse reaction in the subject to which it is administered. This is claiming by a result to be achieved and there is no principle of general application defined in the specification of the AU’002 application that allows a person skilled in the art to identify a suitable iron polyisomaltose complex that has the claimed desired properties alone or in combination. Outside the claims, the specification of the AU’002 application mentions iron polyisomaltose just twice (at [0015] and [0059]). There are no details regarding its manufacture, structure or properties – except for being equated to iron dextrans, which the specification says cannot be administered as required by the amended claims. It is therefore simply implausible by the specification’s own standards that an iron polyisomaltose complex could be administered as required by the amended claims.”[41]
[41] The opponent’s submissions, dated 20 May 2020, at [7.12] – [7.14].

The opponent also submitted that the proposed amendment to increase the amount of elemental iron from at least 0.7 grams to at least 1.1grams is significant and the skilled addressee was well aware at the priority date that a higher dose of elemental iron and faster delivery are associated with a higher risk of adverse events related to the toxicity of the labile iron.[42] The opponent further submitted that no data is provided in relation to the administration, without significant adverse reaction of any compound at the minimum single dosage unit of at least 1.1 grams of elemental iron.[43] Based on their submissions, the opponent argues it is not plausible that the invention could be worked with any carbohydrate complex if administered in accordance with the claims as proposed to be amended.[44]
[42] The opponent’s submissions, dated 20 May 2020, at [7.16], [7.22].
[43] The opponent’s submissions, dated 20 May 2020, at [7.37].
[44] ibid.
The applicant submitted:
“… the specification as-filed teaches how to administer the complex, and specifies the amounts to be administered. The proposed amendment does not result in a change to the disclosure of the invention.”[45]
[45] The applicant’s submissions, dated 27 May 2020, at [23].
As I noted previously, there are no amendments proposed to the description of the present application. The proposed amendments do not result in the removal or addition of any text from the description. Consequently, as a result of the amendments, the disclosure of the invention in the specification has not changed. If there are deficiencies regarding the disclosure of the complete specification, these deficiencies do not arise as a result of the amendments proposed to the claims.
I am satisfied that, if there is a lack of compliance with subsection 40(2), it has not arisen as a result of the amendments. Consequently, the proposed amendments are allowable under paragraph 102(2)(b) with regard to subsection 40(2).
8. Are the amendments allowable under paragraph 102(2)(b) with regard to subsection 40(3)?
Support
The opponent submitted:
“To the extent that there is one, the technical contribution to the art relates to using the complex VIT-45 (Ferinject®, Injectafer®). …
Plainly, all claims as accepted do not correspond to the technical contribution to the art and are therefore not supported by the matter disclosed in the specification of the AU’002 application. However, such a finding lies outside the scope of the Opposition to Amendment where we are concerned only with matters ‘as a result of the proposed amendment’.
Critically, as result of the proposed amendments to claim 1, all of the claims now relate to methods comprising administration of an iron polyiosomaltose complex in a single dosage unit of at least 1.1 grams of elemental iron.⁴¹ The mere mention of iron polyisomaltose just twice in the specification of the AU’002 application (at paragraphs [0015] and [0059]), with no details regarding its manufacture, structure or properties (except for it being equated to iron dextrans, which the specification says cannot be administered as required by the amended claims) does not provide support for what is, on the face of the specification, a relatively high single unit dosage of elemental iron.⁴²
The data in the specification of the AU’002 application in relation to VIT-45 does not even support a single dosage unit of at least 1.1 grams of elemental iron.
In this context, the absence of any data in relation to the administration, without significant adverse reaction, of any compound at the minimum dosage claimed results in the amended claims not being supported by matter disclosed in the specification of the AU’002 application.”[46]
[46] The opponent’s submissions, dated 20 May 2020, at [8.9] – [8.13].
I have previously concluded that as a result of the amendments, new proposed claim 1 now claims matter that is within the scope of claim 1 before the amendment. I am satisfied that, if there is a lack of support, it has not arisen as a result of the amendments.
Clarity and succinctness
The opponent submitted that, as a result of the amendments, proposed claims 2, 3 and 13 are not clear.[47]
[47] The opponent’s submissions, dated 20 May 2020, at [8.16] – [8.24].
Proposed claim 2
I have construed proposed claim 2 above. I am satisfied that, if there is a lack of clarity, it has not arisen as a result of the amendments to this claim.
Proposed claim 3
A marked-up of proposed amendments to claim 3 is reproduced below:
The method of claim 1 or claim 2, wherein the iron carbohydrate complex contains about 24% to about 32% of elemental iron.
The opponent submitted:
“…, there is no indication as to whether the percentage is a percentage by weight of the total complex because no units are included in the claim or in paragraph [0063] of the specification of AU’002 application either as filed or as accepted.
This lack of clarity is compounded by use of the term ‘iron carbohydrate complex’ in claims 4 and 5. Claims 4 and 5 relate to properties of a solution containing the iron carbohydrate complex but are written in such a manner that implies that it is the complex itself that has the specified pH and osmolarity. In light of this, claim 3 also lacks clarity as to whether the percentage of elemental iron is a percentage of the complex or the solution containing the complex. If the percentages are based on the solution, it is not clear whether they are percentages by weight or volume of the solution.”[48]
[48] The opponent’s submissions, dated 20 May 2020, at [8.20] – [8.21].
The specification describes the percentage of elemental iron of iron carbohydrate complexes in the context of their molecular weight. The specification states:
“In various embodiments, the iron carbohydrate complex contains about 24% to about 32% elemental iron; contains about 25% to about 50% carbohydrate; has a molecular weight of about 90,000 daltons to about 800,000 daltons, or some combination thereof. …..
[49] The specification at [0015].
In some preferred embodiments, the iron carboxymaltose complex contains about 24% to about 32% elemental iron, about 25% to about 50% carbohydrate, and is about 100,000 daltons to about 350,000 daltons.”[49]
Regarding the iron carboxymaltose complex, VIT-45, the specification states:
“A preferred pharmaceutical composition for use in the methods described herein contains VIT-45 as the active pharmaceutical ingredient (API) with about 28% weight to weight (m/m) of iron, equivalent to about 53% m/m iron (III)-hydroxide, about 37% m/m of ligand, ≤6% m/m of NaCI, and ≤10% m/m of water.”[50]
[50] The specification at [0094].
I consider that the skilled person would have referred to the description of the invention in the specification and interpreted the percent values in proposed claim 3 to be weight of elemental iron to total weight of the iron carbohydrate complex.
Proposed claim 13
A marked-up of proposed amendments to claim 13 is reproduced below:
The method of any one of claims 1 to 1412, wherein:
the mean iron core size is at least about 1 nm but no greater than about 9 nm; or
the mean size of a particle of the iron carbohydrate complex is no greater than about 35 nm.
The opponent submitted that proposed claim 13 is not clear and succinct as a result of proposed amendment to claim 1 because the feature of the mean iron core size is in now in claim 1 and reference to the feature in claim 13 provides no further limitation over claim 1.[51]
[51] The opponent’s submissions, dated 20 May 2020, at [8.23] – [8.24].
While the mean iron core size is recited in proposed claim 1, the feature of the mean particle size is not defined until claim 13. The scope of proposed claim 13 is different from proposed claim 1 due to the particle size limitation.
I have construed proposed claims 2, 3 and 13 above. I am satisfied that, if there is a lack clarity or lack of succinctness, it has not arisen as a result of the amendments.
Conclusion regarding allowability of amendments under paragraph 102(2)(b)
I conclude the proposed amendments are allowable under paragraph 102(2)(b) with regard to subsections 40(2) and 40(3) and the opponent is unsuccessful in relation to grounds under this paragraph.
9. Conclusion
The opposition under section 104 is unsuccessful on all grounds. I find the amendments allowable under section 102.
10. Costs
It is normal that cost should follow the event. I see no reason to depart from that result. Costs according to Schedule 8 are awarded against Pharmacosmos.
Dr A. Lim
Delegate of the Commissioner of Patents
Annex A: A marked -up copy of the proposed amended claims
The claims defining the invention are as follows:
1. A method of treating a disease, disorder, or condition characterized by iron deficiency or dysfunctional iron metabolism resulting in reduced bioavailability of dietary iron, comprising:
administering to a subject in need thereof an iron carbohydrate complex in a
single dosage unit of at least ~~0.7~~1.1 grams of elemental iron;
wherein:
the iron carbohydrate complex:
-is an iron polyisomaltose complex;
~~the iron carbohydrate complex~~ has a substantially non-immunogenic
carbohydrate component; ~~and~~
has substantially no cross reactivity with anti-dextran antibodies;
comprises an iron core having a mean iron core size of at least about 1 nm but
no greater than about 9 nm;
and wherein the subject does not experience a significant adverse reaction to the
single dosage unit administration.
2. A method of claim 1, wherein the ~~iron carbohydrate complex has substantially no cross reactivity with anti-dextran antibodies.~~single dosage unit of elemental iron is:
i) at least 1.1 grams to about at least 2.5 grams; or
ii) at least about 1.1 grams to at least 1.5 grams; or
iii) about 1.5 grams; or
iv) at least 1.5 grams; or
v) up to about 2.0 grams.
3. The method of claim 1 or claim 2, wherein the iron carbohydrate complex contains
about 24% to about 32% of elemental iron.
34. The method of any one of claims 1 to 3~~or claim 2~~, wherein the iron carbohydrate
complex has a pH from about 5.0 to about 7.0.
45. The method of any one of claims 1 to 34, wherein the iron carbohydrate complex
has physiological osmolarity.
56. The method of any one of claims 1 to 45, wherein the disease, disorder, or condition
comprises anemia.
67. The method of claim 56, wherein the anemia comprises iron deficiency anemia.
78. The method of claim 56, wherein:
(i) the anemia comprises an iron deficiency anemia associated with chronic blood loss; anemia associated with acute blood loss; anemia associated with pregnancy; anemia associated with childbirth; anemia associated with childhood development; anemia associated with psychomotor and cognitive development in children; anemia associated with breath holding spells; anemia associated with heavy uterine bleeding; anemia associated with menstruation; anemia associated with chronic recurrent hemoptysis; anemia associated with idiopathic pulmonary siderosis; anemia associated with chronic internal bleeding; anemia associated with gastrointestinal bleeding; parasitic infections; anemia associated with chronic kidney disease; anemia associated with dialysis; anemia associated with surgery or acute trauma; anemia associated with chronic ingestion of alcohol; anemia associated with chronic ingestion of salicylates; anemia associated with chronic ingestion of steroids; anemia associated with chronic ingestion of non-steroidal anti-inflammatory-agents, or anemia associated with chronic ingestion of erythropoiesis stimulating agents;
(ii) the anemia associated with a chronic disease selected from the group consisting of anemia associated with rheumatoid arthritis; cancer; anemia associated with Hodgkins leukemia; anemia associated with non-Hodgkins leukemia; anemia associated with cancer chemotherapy; anemia associated with inflammatory bowel disease; anemia associated with ulcerative colitis thyroiditis; anemia associated with hepatitis; anemia associated with systemic lupus erythematosus; anemia associated with polymyalgia rheumatica; anemia associated with scleroderma; anemia associated with mixed connective tissue disease; anemia associated with Sojgren's syndrome; anemia associated with congestive heart failure/cardiomyopathy; and idiopathic geriatric anemia;
(iii) anemia associated with impaired iron absorption or poor nutrition;
(iv) anemia associated with Crohn's Disease; anemia associated with gastric surgery; anemia associated with ingestion of drug products that inhibit iron absorption; or anemia associated with chronic use of calcium.
89. The method of any one of claims 1 to 67, wherein the disease, disorder, or condition is selected from the group consisting of anemia associated with restless leg syndrome; anemia associated with blood donation; Parkinson's disease; anemia associated with hair loss; and anemia associated with attention deficit disorder.
910. The method of any one of claims 1 to 67, wherein the disease, disorder, or condition
is anemia associated with congestive heart failure/cardiomyopathy.
~~10. The method of any one of claims 1 to 8, wherein the single dosage unit of elemental~~
~~iron is at least 5 about 1.0 grams.~~
~~11. The method of any one of claims 1 to 8, wherein the single dosage unit of elemental~~
~~iron is at least about 1.5 grams.~~
~~12. The method of any one of claims 1 to 8, wherein the single dosage unit of elemental~~
~~iron is at least about 2.0 grams.~~
1311. The method of any one of claims 1 to 1210, wherein the single dosage unit of elemental iron is administered in about 15 minutes or less.
1412. The method of any one of claims 1 to 1210, wherein the single dosage unit of elemental iron is administered in about 5 minutes or less.
1513. The method of any one of claims 1 to 1412, wherein:
the mean iron core size is at least about 1 nm but no greater than about 9 nm; or
the mean size of a particle of the iron carbohydrate complex is no greater than
about 35 nm.
1614. The method of any one of claims 1 to 1513, wherein the iron carbohydrate complex is administered parenterally.
1715. The method of claim 1614, wherein:
(i) parental administration comprises intravenous infusion and the single unit dose of iron carbohydrate complex is administered at a concentration of about 1000 mg elemental iron in about 200 ml to about 300 ml of diluent;
(ii) parenteral administration comprises bolus injection and the single unit dose of iron carbohydrate complex is administered at a concentration of about 1000 mg elemental iron in about 200 ml to about 300 ml of diluent; or
(iii) parenteral administration comprises intramuscular injection and the single unit dose of iron carbohydrate complex is administered at a concentration of about 500 mg elemental iron in less than about 10 ml diluent.
1816. The method of any one of claims 1 to 1715, further comprising a second administration of said iron carbohydrate complex upon recurrence of at least one symptom of the disease, disorder, or condition.
~~19. The method of any one of claims 1 to 18, wherein the single unit 5 dosage is at least about 0.6 grams up to about 2.0 g of elemental iron.~~
~~20. The method of any one of claims 1 to 18, wherein the single unit dosage is at least about 0.8 grams up to about 2.0 g of elemental iron.~~
~~21. The method of any one of claims 1 to 18, wherein the single unit dosage is at least about 1.0 grams up to about 2.0 g of elemental iron.~~