As a growing number of biological enterprises pay attention to and use the international patent application procedure, it is becoming more and more important for them to know and apply the biological collection and genetic sequence listing issues involved in this procedure. In this article, we will briefly introduce the relevant issues, so that the patent applicants may understand the issues involved in patent applications that relate to biological collection and genetic sequence listing, avoid the rejection of patent applications due to inadequate disclosure in the following national stage, and learn how to reduce the cost of patent applications.

I. Specific Provisions on Patent Applications Involving Biological Collection and Relevant Issues

The Regulations under the Patent Cooperation Treaty (as in force from 1 July 2004) cover the issues related to the deposit of biological material in Rule 13bis "Inventions Relating to Biological Material", specifically as follows:

"Reference to deposited biological material" means particulars given in an international application with respect to the deposit of biological material with a depositary institution or to the biological material so deposited. As for the effect of the reference to deposited biological material, it provides that: any reference to deposited biological material shall be made in accordance with this Rule and, if so made, shall be considered as satisfying the requirements of the national law of each designated State.

In addition, the Rule also provides the content of the reference to deposited biological material, including: (a) a reference to deposited biological material shall indicate: (i) the name and the address of the depositary institution with which the deposit was made; (ii) the date of deposit of the biological material with that institution; (iii) the accession number given to the deposit by that institution; and (iv) any additional matter of which the International Bureau has been notified pursuant to Rule 13bis.7(a)(i), provided that the requirement to indicate such matter was published in the Gazette in accordance with Rule 13bis.7(c) at least two months before the filing of the international application.

As for the time limit for furnishing indications of the reference to deposited biological material, the Rule provides: (a) Subject to paragraphs (b) and (c), if any of the indications referred to in Rule 13bis.3(a) are not included in a reference to deposited biological material in the international application as filed but is furnished to the International Bureau: (i) within 16 months from the priority date, the indication shall be considered by any designated Office to have been furnished in time; (ii) after the expiration of 16 months from the priority date, the indication shall be considered by any designated Office to have been furnished on the last day of that time limit if it reaches the International Bureau before the technical preparations for international publication have been completed. (b) If the national law applicable to a designated Office so requires in respect of national applications, that Office may require that any of the indications referred to in Rule 13bis.3(a) be furnished earlier than 16 months from the priority date, provided that the International Bureau has been notified of such requirement pursuant to Rule 13bis.7(a)(ii) and has published such requirement in the Gazette in accordance with Rule 13bis.7(c) at least two months before the filing of the international application. (c) Where the applicant makes a request for early publication under Article 21(2) (b), any designated Office may consider any indication not furnished before the technical preparations for international publication have been completed as not having been furnished in time. (d) The International Bureau shall notify the applicant of the date on which it received any indication furnished under paragraph (a), and: (i) if the indication was received before the technical preparations for international publication have been completed, publish the indication furnished under paragraph (a), and an indication of the date of receipt, together with the international application; (ii) if the indication was received after the technical preparations for international publication have been completed, notify that date and the relevant data from the indication to the designated Offices.

Furthermore, the Rule also provides the references and indications for the purposes of one or more designated states; different deposits for different designated states; deposits with depositary institutions other than those notified: (a) A reference to deposited biological material shall be considered to be made for the purposes of all designated States, unless it is expressly made for the purposes of certain of the designated States only; the same applies to the indications included in the reference. (b) References to different deposits of the biological material may be made for different designated States. (c) Any designated Office may disregard a deposit made with a depositary institution other than one notified by it under Rule 13bis.7(b). To protect the interests of the depositor of deposited biological material, the Rule provides the furnishing of samples in 13bis.6: Pursuant to Articles 23 and 40, no furnishing of samples of the deposited biological material to which a reference is made in an international application shall, except with the authorization of the applicant, take place before the expiration of the applicable time limits after which national processing may start under the said Articles. However, where the applicant performs the acts referred to in Article 22 or 39 after international publication but before the expiration of the said time limits, the furnishing of samples of the deposited biological material may take place, once the said acts have been performed. Notwithstanding the previous provision, the furnishing of samples of the deposited biological material may take place under the national law applicable to any designated Office as soon as, under that law, the international publication has the effect of the compulsory national publication of an unexamined national application.
 

On the basis of the relevant provisions on the deposit of biological material in Rule 13bis "Inventions Relating to Biological Material" of the Regulations under the Patent Cooperation Treaty, the Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purposes of Patent Procedure was concluded in Budapest, the capital of Hungary, on 28 April 1977 and formally entered into force on 19 August 1980. China acceded to the Budapest Treaty on 1 July 1995. The main characteristics of the Budapest Treaty are that the Contracting States which allow or require the deposit of microorganisms for the purposes of patent procedure shall recognize, for such purposes, the deposit of a microorganism with any international depositary authority, no matter whether the "international depositary authority" is within its territory or not. It exempts the patent applicant from the trouble of depositing the microorganism with each State where he seeks protection and allows him to obtain the recognition of other Contracting States as regards the deposit of the microorganism during the patent application.

In accordance with the Instrument of Accession to the Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purposes of Patent Procedure (hereinafter the "Budapest Treaty") submitted by China's government to the Director General of the World Intellectual Property Organization (WIPO) on 30 March 1995 and the Communication of the People's Republic of China Relating to the Acquisition of the Status of International Depositary Authority by the China General Microbiological Culture Collection Center (CGMCC) and by the China Center for Type Culture Collection (CCTCC) submitted to the Director General of the WIPO by Mr. Gao Lulin, director of the Patent Office of China, on the same date, China became a member of the Budapest Treaty as of 1 July 1995 and the above two institutions also acquired the status of international depositary authority under the Budapest Treaty as from 1 July 1995. 

The Guide to the Deposit of Microorganisms under the Budapest Treaty of the China General Microbiological Culture Collection Center (CGMCC) (hereinafter the "Guide")[1] provides the kinds of microorganisms that may be deposited: the CGMCC accepts the deposit of the following microorganisms. With the exception of pathogenic microorganisms of Risk Group 1 (Chinese classification): bacteriayeasts, filamentous fungi, animal viruses*, plant viruses*, anaerobic microorganisms, single cell algae, animal cell lines, plant cell lines, mycoplasma, viruses, bacteriophages, plasmids and plant seeds.

At present, the CGMCC does not accept temporarily the following biological material for deposit:

Protozoa: microorganisms that are prohibited from import according to Chinese law; microorganisms whose conservation involves hazards deemed to be excessive. As a general rule, the CGMCC will accept only strains that can be placed in a culture under conditions technically feasible for the collection concerned and conserved, other than in continuous vegetative activity, without inducing significant changes in their characteristics. Exceptionally, the CGMCC may accept deposits that cannot be conserved other than by active culture, but acceptance of such a deposit will have to be decided upon, and the relevant fee determined, on a case-by-case basis, after prior negotiation with the potential depositor. Notwithstanding this, the CGMCC may accept or refuse the deposit of any biological material at the discretion of its director. The CGMCC will indicate the reason for rejection as there existing a hazard or difficulty in operation. (* The viability test of some animal viruses requires the host animal, which cannot be provided by the CGMCC. In such cases, the application for deposit will be refused. Plant viruses that cannot reproduce mechanically will also be refused.)
 

The Guide also provides the technical requirements and the procedure: cultures of microorganisms are accepted by the CGMCC in any form. The minimum number of replicates that must be provided by the depositor when making his deposit is as follows: Bacteria, yeasts, filamentous fungi, phages, mycoplasma and single cell algae: 5; Viruses, plasmids (not cloned into a host), animal cell lines and plant cell lines: 15; Plant seeds: 2,000.

The average length of time required for testing the viability of the various kinds of microorganisms accepted by the CGMCC is given below, but depositors should realize that in some cases viability testing may take longer, as indicated by the figures in brackets: Bacteria, yeasts: 3 days (or up to 20 days); Filamentous fungi and mycoplasma: 6 days (or up to 30 days); Phages, single cell algae and animal cell lines: 7 days (or up to 14 days); Plasmids*: 8 days (or up to 10 days); Animal viruses, plant cell lines and plant seeds: 21 days (or up to 30 days); Plant viruses: no date as yet. (*For plasmids, "viability" testing consists of inserting the plasmid into a host. If the host is transformed, the "viability test" is regarded as positive.)

The Guide also provides the depositor checks and renewal of stocks: the CGMCC prepares its own lyophilized and/or frozen batches at the time of deposit of bacteria, actinomycetes, yeasts, filamentous fungi, phages, single cell algae and, in some cases, viruses, by subculture of, or directly from, active material supplied by the depositor. New batches are prepared as necessary for the renewal of diminishing stocks. The CGMCC stores and distributes lyophilized material supplied by the depositor, if this is his wish. The CGMCC generally does not prepare its own batches of animal viruses and plasmids. In such cases, when stocks of material are depleted by the furnishing of samples, the CGMCC will ask the depositor to make a new deposit. The CGMCC requires the depositor to check the authenticity of its lyophilized preparations. The viability statement issued by the CGMCC contains a section in which the depositor can record the result of this test. If the depositor does not inform the CGMCC of the results of this test within three months, the CGMCC assumes that its preparations are equivalent to the depositor's original deposit. Whichever method is used for preparing batches of samples for distribution, the CGMCC stores a portion of the original prepared and deposited material.
 

The Guide also provides that depositors are required to complete CGMCC form BP/1 "Budapest Treaty Deposits" in all cases. The CGMCC does not require a special form to be completed in the event of a later indication or amendment of the scientific description and/or proposed taxonomic designation, or for a request for attestation that the CGMCC has received such information. The receipt and viability statements are issued on mandatory "international forms" BP/4 and BP/9, respectively.

The Guide provides that deposits made outside the provisions of the Budapest Treaty may be converted by the original depositor to Budapest Treaty deposits, whether or not they were originally deposited for patent purposes; however, any deposits previously made free of charge are subject on conversion to the storage fees normally levied for Budapest Treaty deposits. The administrative requirements for conversion are the same as those to be met in respect of an original deposit made under the Budapest Treaty, except that requirements relating to import and/or quarantine procedures do not apply. The Guide also provides that the CGMCC may accept a new deposit under Article 4 of the Budapest Treaty and Rule 6.2 of the Regulations under the Treaty.

The Guide provides that the CGMCC will furnish samples to interested industrial property offices, the depositor or parties with the authorization of the depositor and parties legally entitled under Rule 11.3 of the Regulations under the Budapest Treaty. Except for animal viruses and plasmids, the CGMCC furnishes samples of its own preparations of the deposited microorganism.

Similarly, the applicants and inventors may, on the basis of the types of their biological samples to be deposited and their geological locations, apply to the China Center for Type Culture Collection (CCTCC) for the deposit of biological samples. The specific requirements may be obtained from the CCTCC's website. [2]

Therefore, the applicant and inventor need to confirm whether his application involves the deposit of biological material while preparing the material for patent application if he wishes to submit the PCT application. If it involves the deposit of biological material, it is advisable to deposit the relevant biological material while or before drafting the patent application (and it would be optimal to receive the deposit certificate and the viability certificate issued by a depositary authority under the Budapest Treaty), so as to avoid the risk of inadequate disclosure of the relevant patent application due to lack of viable biological material on or after the date of patent application.

If it is the case that the biological material loses viability during the application for a PCT patent, the applicant may re-deposit the biological material with the depositary authority under the Budapest Treaty, and then re-submit the PCT application and claim the priority right of the original PCT application after receiving the deposit certificate and the viability certificate, so that the subsequent PCT application will have the date of priority right of the original application except for the deposit of biological material and is prevented from risk of inadequate disclosure of the relevant patent application.
 

In addition, it should be noted that if the deposit is not made under the Budapest Treaty, it may be transferred to a deposit under the Budapest Treaty at the request of the original depositor, provided that the deposit date of the biological material under the Budapest Treaty is the date of transfer. To prevent ordinary biological material deposited for the purpose of patent application from becoming an existing technology of the PCT application due to advance disclosure for a prior patent application in China, it is advisable for the applicant to apply for the deposit of biological material under the Budapest Treaty from the very beginning.

Furthermore, when the PCT application involving the deposit of biological material enters the stage of national application, as each national or regional patent office may have different requirements, the applicant should pay attention to the relevant requirements of each national or regional patent office on the national stage of a PCT application involving the deposit of biological material, e.g. according to Article 108 (1) of the Implementation Rules of the Patent Law of the People's Republic of China,[3] if the applicant has made a statement on the deposit of the sample of biomaterial in accordance with the Patent Cooperation Treaty, he/it shall be deemed to have met the requirements of Article 24 (3) of the Implementation Rules. The applicant shall state in the declaration for entry into the National Phase in China the documents recording the matters on the deposit of the sample of the biomaterial and the specific location of the record in the documents.

If the deposit recorded in the description is not in the form of a table, the applicant shall indicate, in the designated column of the statement of entry, the specific page and line of the record in the translation of the description. The examiner will review the relevant content of the translation. If the deposit is recorded in the "Indications Relating To a Deposited Microorganism" (Form PCT/RO/134) or on a separate sheet, the Form or sheet shall be contained in the international publication text. If the examinant finds that the deposit is not recorded in the designated place of the translation as indicated in the statement of entry or the "Indications Relating To a Deposited Microorganism" (Form PCT/RO/134) or the separate sheet as indicated in the statement of entry is not included in the international publication text, he shall issue a notice regarding the biological sample that it is deemed not deposited. Due to the special procedure of international application, the period for submitting the deposit certificate and the viability certificate of biological material shall be four months from the date of entry.
 

II. Specific Provisions on Patent Applications Involving Genetic Sequence Listing and Relevant Issues

The Regulations under the Patent Cooperation Treaty provide the disclosure of nucleotide and/or amino acid sequences in Rule 5 "The Description": (a) Where the international application contains disclosure of one or more nucleotide and/or amino acid sequences, the description shall contain a sequence listing complying with the standard provided for in the Administrative Instructions and presented as a separate part of the description in accordance with that standard. (b) Where the sequence listing part of the description contains any free text as defined in the standard provided for in the Administrative Instructions, that free text shall also appear in the main part of the description in the language thereof.

In addition, the Regulations under the Patent Cooperation Treaty also provide the "Nucleotide and/or Amino Acid Sequence Listings" in Rule 13ter: (a) Where the international application contains disclosure of one or more nucleotide and/or amino acid sequence, the International Searching Authority may invite the applicant to furnish it, for the purposes of the international search, a sequence listing in electronic form complying with the standard provided for in the Administrative Instructions, unless such listing in electronic form is already available to it in a form and manner acceptable to it, and to pay to it, where applicable, the late furnishing fee referred to in paragraph (c), within a time limit fixed in the invitation. (b) Where at least part of the international application is filed on paper and the International Searching Authority finds that the description does not comply with Rule 5.2(a), it may invite the applicant to furnish, for the purposes of the international search, a sequence listing in paper form complying with the standard provided for in the Administrative Instructions, unless such listing in paper form is already available to it in a form and manner acceptable to it, whether or not the furnishing of a sequence listing in electronic form is invited under paragraph (a), and to pay, where applicable, the late furnishing fee referred to in paragraph (c), within a time limit fixed in the invitation. (c) The furnishing of a sequence listing in response to an invitation under paragraph (a) or (b) may be required by the International Searching Authority to pay to it, for its own benefit, a late furnishing fee whose amount shall be determined by the International Searching Authority but shall not exceed 25% of the international filing fee referred to in item 1 of the Schedule of Fees, not taking into account any fee for each sheet of the international application in excess of 30 sheets, provided that a late furnishing fee may be required under either paragraph (a) or (b) but not both. (d) If the applicant does not, within the time limit fixed in the invitation under paragraph (a) or (b), furnish the required sequence listing and pay any required late furnishing fee, the International Searching Authority shall only be required to search the international application to the extent that a meaningful search can be carried out without the sequence listing. (e) Any sequence listing not contained in the international application as filed, whether furnished in response to an invitation under paragraph (a) or (b) or otherwise, shall not form part of the international application, but this paragraph shall not prevent the applicant from amending the description in relation to a sequence listing pursuant to Article 34(2)(b). (f) Where the International Searching Authority finds that the description does not comply with Rule 5.2(b), it shall invite the applicant to submit the required correction. Rule 26.4 shall apply mutatis mutandis to any correction offered by the applicant. The International Searching Authority shall transmit the correction to the receiving Office and to the International Bureau.

In addition, it also provides that: Rule 13ter.1 shall apply mutatis mutandis to the procedure before the International Preliminary Examining Authority. No designated Office shall require the applicant to furnish to it a sequence listing other than a sequence listing complying with the standard provided for in the Administrative Instructions.
 

The Administrative Instructions under the Patent Cooperation Treaty contains the provisions on the following issues in the relevant paragraphs on "Nucleotide and/or Amino Acid Sequence Listings" of Section 204, Section 207 and Section 208: the headings of the parts of the description shall preferably be named "Sequence Listing" or "Sequence Listing Free Text"; the description may include the sequence listing free text or the sequence listing part of the description; any sequence listing, whether on paper or in electronic form, whether forming part of the international application or not, shall comply with Annex C. Annex C of the Administrative Instructions under the Patent Cooperation Treaty provides the Standard for the Presentation of Nucleotide and Amino Acid Sequence Listings in International Patent Applications under the PCT. Specifically, it provides that: the sequence listing (i) shall be presented as a separate part of the description, be placed at the end of the application, preferably be entitled "Sequence Listing", begin on a new page and have an independent page; preferably, the sequence listing shall not be reproduced in any other part of the application; it is unnecessary to describe the sequences elsewhere in the description; (ii) shall present the sequences represented in the sequence listing and other available information in the sequence listing in accordance with paragraphs 5 to 35; (iii) if contained in an international application filed in electronic form, shall be in an electronic document format and filed by means of transmittal in accordance with paragraph 37.

On the basis of the above provisions, if the international application involves the relevant content of the "nucleotide and/or amino acid sequence listings", the applicant shall, while drafting the patent application, use acceptable software (e.g. any version of PatentIn) to generate the relevant nucleotide and/or amino acid sequence listings pursuant to the requirements, so as to be submitted as a separate part of the description; and the content of the sequence listings need not be copied in the description, thus reducing the total pages of the international application and the total application fee. Furthermore, it also avoids the additional fee for late submission.

When the international application enters the national stage of China, the sequence listings shall be added to the description to calculate the total number of pages. If the description, the drawings annexed to the description and the sequence listings exceed 30 pages, then an additional fee shall be paid. As the sequence listings may exceed 400 pages in some patent applications, the State Intellectual Property Office of the PRC provides that the applicant need only submit the sequence listings in electronic form (also called computer readable form), i.e. the sequence listings in TXT form in such cases, and the whole sequence listings will be deemed as comprising 400 pages, thus reducing the additional fee for the description and the expenses of the applicant.

The above is just a preliminary description of the relevant issues on the basis of the author's understanding of the patent application procedure involving the deposit of biological material and sequence listings, in the hope of facilitating applicants' understanding of patent applications involving the deposit of biological material and sequence listings, preventing patent applications from being rejected in the subsequent national stages due to inadequate disclosure, and helping applicants to know how to reduce the cost of patent applications, so as to stimulate more and more biological enterprises to pay attention to and use the relevant procedure of international patent application.

[1] The Guide to the Deposit of Microorganisms under the Budapest Treaty, refer to the website of the China General Microbiological Culture Collection Center (CGMCC):
http://www.cgmcc.net/serve/guide.html.
[2] Refer to the website of the China Center for Type Culture Collection (CCTCC): http://www.cctcc.org/cctcc.php.
[3] Guidelines for Patent Examination (2010), prepared by the State Intellectual Property Office of the People's Republic of China, published by the Intellectual Property Publishing House, September 2009, p332.