Patent Court Decision, 2017Heo2277, dated September 28, 2017
PATENT COURT OF KOREA
SECOND DIVISION
DECISION
Case No.: 2017Heo2277 Rejection (Patent)
Plaintiff: A
Taiwan
Defendant: Commissioner of the Korean Intellectual Property Office (the “KIPO”)
Date of Closing Argument: August 29, 2017
Decision Date: September 28, 2017
ORDER
1. The IPTAB Decision 2015Won4737 rendered on January 31, 2017 shall be revoked.
2. The cost arising from this litigation shall be borne by the Defendant.
PLAINTIFF’S DEMAND
As ordered.
OPINION
1. Facts
A. Claimed Invention at Issue (Plaintiff's Exhibit 2, Defendant's Exhibit 1)
1) Title of Invention: A METHOD FOR PREPARING A BIOMATERIAL
2) International Filing Date/ Translation Filing Date/ Application Number February 15, 2008/ August 6, 2010/ 2010-7017516
3) Claim Construction (as finally amended on August 17, 2015)
[Claim 1]
A method for preparing a tissue repair material from scales, comprising the step of: acellularizing1)) a fish scale to remove some of the albumin2)) and glycosaminoglycan3)); grinding the fish scale into a plurality of ground particles (hereinafter referred to as “Element 1”), wherein the ground particles contain a mixture of sponge like matrix and powder (hereinafter referred to as “Element 2”).
[Claims 2 to 28] Omitted
4) Main Content and Drawing
[1] Technical field and prior art
The present invention relates to a biomaterial and preparation method thereof, and particularly to a biomaterial prepared from fish scales for use in tissue repair and implantation.
The biomaterial is a synthetic and biocompatible material that is used to construct artificial organs, rehabilitation devices, or prostheses and replace natural body tissues. For over decades, collagen fiber, hydroxyapatite (HAP) and tri-calcium phosphate (TCP) are some biomaterials with great biocompatibility and safety to be used in human tissue implants. However, these biomaterials have disadvantages such as low mechanical strength, risk of chemical residue in cross linking, terrestrial animal transmitted diseases (paragraphs [0001] to [0003] of the specification).
[2] Technical problem to be solved and solution
It is an aspect of the invention to provide a biomaterial having a high mechanical strength, low possibility of contracting terrestrial contagious diseases and is applicable to tissue repair or implants.
It is an aspect of the invention to provide a biomaterial prepared from fish scales by a process which includes acellularizing the fish scales; and grinding the fish scales into ground particles, wherein each of the ground particles contain a mixture of sponge like matrix and powder.
The fish scale could have an average diameter of less than 20 cm. For example, the fish scales can have a diameter of about 10-20 cm. The fish scales could be grinded into smaller sizes for special use. For example, the average size of the ground particles can be less than about 10 ㎛ in diameter (paragraphs [0005], [0008], [0011] to [0013] of the specification).
[3] Effects of the invention
The biomaterial derived by the methods illustrated above retains the original bonding and the 3D structure of the fish scales, and therefore, it has a high mechanic strength, low possibility of contracting terrestrial contagious diseases and is applicable in repairing tissue or tissue implants (paragraph [0018] of the specification).
B. Reference (Defendant's Exhibit 2)
An article entitled “Preparation and partial characterization of a collagen sheet from fish (Lates calcarifer) scales” published in “International Journal of Biological Macromolecules, Vol 42” on January 1, 2008. The main content and drawing thereof are as follows.
[1] Summary
Fish scales, which are hitherto discarded as waste, were collected and cleaned thoroughly. The scales were hydrolyzed under controlled acidic conditions, neutralized and made in to a sheet, i.e., fish scale collagen1)) sheet (FCS). The FCS was characterized through infrared spectroscopy (IR), thermo-gravimetric analysis (TGA), scanning electron microscopy (SEM), and its mechanical properties were also analyzed. The IR study has shown that the sheet contains both organic and inorganic phases revealing that the scales are partially demineralized. The tensile strength of FCS is enough so that it could be used as a wound dressing material. The SEM studies have shown that FCS is porous and exhibited a fibrous nature (Abstract on page 6).
[2] Materials and Methods
Dry fish scales were treated with different concentrations of HCl solutions (1:1, v/w, water/fish scales; i.e., 100 ml water/100 g fish scales; Table 1) for 24 h at room temperature (34±2 ◦C). Later, the acid solution was decanted and the scales were washed with water. Then water was added to the scales (2:1,v/w) and the pH of the scales was adjusted to 7 using a 0.1N NaOH solution (to check the pH, a sample scale was cut vertically, pH paper was inserted and the pH was noted). Further, scales were washed with water and pulverized with a float of 1:1 (v/w, water/scales) using a domestic mixer for 15 min at 12,000 rpm (the scales treated with 2.81N HCl solution could be pulverized and made into paste), and the resulting paste was cast into a sheet in a polythene tray and dried at room temperature (34±2 ◦C). The dried sheets are stored in polythene covers for further studies (2.2. Methods on page 7 and Fig. 1).
[3] Results and Discussion
SEM images of the collagen sheet (Figs. 4 and 5) showed its fibrous and porous nature. As the mineral present in the scale was partially dissolved by acid, the porous nature of the sheet was clearly seen. The fibrillar structure of collagen present in the sheet and its organization were clearly viewed (left column, 3rd paragraph on page 8).
The main objective of the preparation of FCS is to use it as a wound dressing material (left column, 2nd paragraph on page 9). The porous nature of sheet will help to absorb the wound fluid when it is applied on the wound thereby keeping the wound dry. This property helps in enhancing the rate of healing of the wound (right column, 1st paragraph on page 9).
C. The Decision Below
1)On July 29, 2014, the KIPO examiner issued a Notice of Preliminary Rejection on the grounds that Claims 1 to 11 before amendment do not meet the description requirements under Article 42(4)(i) of the Patent Act and Claims 1 to 22 do not meet the description requirements under Article 42(4)(ii) of the Patent Act, and thus, the application cannot be allowed.
In response, the Plaintiff submitted a response and an amendment on September 29, 2014. However, on February 27, 2015, the KIPO examiner issued a second Notice of Preliminary Rejection on the grounds that all of the claims would have been easily conceived by a skilled person in the art, and thus, the application cannot be allowed under Article 29(2) of the Patent Act.
In response, the Plaintiff submitted a response and an amendment on May 26, 2015. However, on July 17, 2015, the KIPO examiner issued a Final Rejection on the grounds that the previous rejection grounds have not yet been resolved.
2)The Plaintiff filed an appeal against the Final Rejection before the IPTAB on August 17, 2015 with the submission of an amendment for re-examination (Case No. 2015Won4737). However, on October 12, 2015, the KIPO examiner issued the re- examination decision upholding the Final Rejection.
The IPTAB examined the case and dismissed the Plaintiff’s appeal on the grounds that “Claim 1 does not have any special objective over the prior art, is not considered to have any constitutional difficulty, and cannot be regarded as having unexpectedly superior effects, and thus, is not recognized to have inventiveness over the prior art. If even a single claim is to be subject to rejection, the application shall be rejected as a whole” on January 31, 2017.
[Factual Basis] Undisputed facts, Statements in Plaintiff's Exhibits 1 to 5, Defendant's Exhibits 1 and 2, and the purport of the overall argument
2. Summary of the Parties’ Arguments
A. The Plaintiff’s Arguments
Claim 1 is not easily conceivable from the prior art in view of differences in the technical field, objective, constitution, and effects from the prior art as detailed below, and thus, inventiveness of Claim 1 is not denied. However, the IPTAB decision is inconsistent with this and thus is erroneous.
1) Claim 1 is directed to a method for preparing a tissue repair material from scales, comprising the step of “acellularizing a fish scale for removing some of the albumin and glycosaminoglycan.” Even after the acellularizing step, the original bonding and the 3D structure of the extracellular matrix are retained, mechanical strength is high, and immune rejection response of a host is not present. Thus, the claimed invention has superior effects with respect to tissue cultivation.
2) In contrast, the prior art relates to a method for preparing a wound dressing sheet having a function of absorbing wound fluid into the pores by utilizing the porous structure of the collagen sheet formed from decalcification. In this regard, the HCl treatment step in the prior art is simply for decalcification4)), and the step of acellularizing is not suggested or implied. Moreover, after the HCl treatment step, the collagen of fish scales is dissolved, glycosaminoglycan is removed, and even the original bonding and the 3D structure are destroyed, whereby the structural strength of the resulting product becomes very weak.
B. The Defendant’s Arguments
Claim 1 would have been easily conceived from the prior art for the following reasons and the inventiveness thereof is denied accordingly. Thus, the IPTAB decision is consistent with this and shall be upheld.
1) Even if the step of acellularizing is not disclosed in the prior art in the process of preparing a collagen sheet for wound dressing, it is essential to remove cells present in fish scales in order to avoid the adverse effects of the immune rejection response which may occur in a collagen sheet, a medical product applied to the human body.
Further, HCl is an acellularizing agent which is frequently used in this technical field. Thus, the HCl treatment step in the prior art involves acellularization. In addition, since glycosaminoglycan is widely known in this technical field to be a protein for use in cell repair, utilizing the extract of collagen and glycosaminoglycan from fish scales as biomaterials is obvious to a skilled person in the art at the time of the filing date of the application.
2) The collagen sheet prepared from the HCl treatment in the prior art is not very different from Claim 1 with respect to the structure and strength. Moreover, there is no big difference in terms of biocompatibility and immune response after acellularization occurs. Thus, the effects expected from Claim 1 is predictable from the prior art.
3. Inventiveness of Claim 1
A. Element-by-element Comparison
B. Commonalities and Differences
1)The technical field of Claim 1 and the prior art is broadly similar in that both are directed to a method for preparing biocompatible biomaterials from fish scales. Claim 1 and the prior art are also the same in that the fish scale is grinded after being subject to a certain process, as shown in Element 2 and the corresponding element of the prior art.
2) However, the resultant product of Claim 1 is “a tissue repair material,” whereas the prior art relates to a method for preparing collagen sheet for wound dressing. As such, the specific technical field is different from each other.
In addition, Claim 1 recites “the step of acellularizing a fish scale for removing some of the albumin and glycosaminoglycan, “ whereas the prior art only discloses a process of preparing a collagen sheet through HCl treatment without reciting “acellularization.” It will be discussed below whether Claim 1 is easily conceivable by a skilled person in the art from the prior art despite such differences.
C. Analysis of the Differences
It is difficult to recognize that Claim 1 is easily conceivable by a skilled person in the art from the prior art for the following reasons.
1) Claim 1 is a method for preparing a tissue repair material, which is used to repair tissue damages, as shown in the descriptions of the specification below:
The biomaterial of the invention contains tissue repair factors and may be manufactured into a tissue repair material for repairing a variety of tissue damages and tissue defect sites. In other examples, the biomaterial may be made as a dressing for transplantation, implantation on surgical grafts or implants to be implanted at, into, onto or near bone defect sites, cartilage repair sites or other tissue defect sites. Summarizing the above, the invention relates to a biomaterial in powder and/or matrix and/or flaky form prepared from the fish scales 9 for use in a variety of tissue repairs and implantations (paragraphs [0028], [0029]).
In contrast, the prior art relates to a method for preparing a wound dressing sheet applicable to wound sites such that the wound does not become worse and is rapidly cured. Thus, the resultant product and the application field of the prior art are different from those of Claim 1, and the technical constitution and the effects of the prior art are different from those of Claim 1 accordingly.
2) First, a tissue repair material, the resultant product of Claim 1, is used for tissue damage inside as well as outside the body and is required to have the capability to repair tissues and facilitate implantation. For this purpose, Claim 1 recites the step of acellularization.
In contrast, the prior art aims to increase wound repair rate by forming pores in a collagen sheet and absorbing wound fluid to make the wound sites dry. For that purpose, the prior art only discloses a process of preparing a collagen sheet by subjecting fish scales to partial decalcification with a 25% HCl solution to make the scales into a paste, but does not suggest or imply acellularization at all.
3)Meanwhile, acellularization is essential for solving the problems of the immune rejection response which may occur when biomaterials obtained from other animals are applied to the human body, and it is possible that acellularization of fish scales is accompanied during the process of the HCl treatment of the prior art. However, a skilled person in the art knowing the prior art would not have been motivated to conceive of a method for preparing a tissue repair material as recited in Claim 1 or readily would have arrived at Claim 1 from the constitution of the prior art, because the prior art is directed to a wound dressing sheet and does not describe acellularization at all.
Further, the prior art only focuses on the concentration of the HCl solution under which the fish scales could be made into a paste, as can be seen from Table 1 of the prior art. Accordingly, the prior art just analyzes whether the fish scales can be made into a paste while not being dissolved at 20%, 25% and 30% HCl solutions. Even Defendant's Exhibit 12, which was submitted to prove that the HCl solution is used as an acellularizing agent, utilized a low concentration (0.1M, 0.365%)5) of HCl solution for acellularization. In view of this, it appears difficult to recognize that a skilled person in the art would be motivated to conceive of acellularization from the prior art utilizing a high concentration (25%) of HCl solution.
[Table 1] Effect of HCl solution on fish scales
In addition, as can be seen from Defendant's Exhibit 11, there is a problem that glycosaminoglycan is dissociated from the collagen tissue with an acid treatment for acellularization. In this regard, unlike Claim 1, the prior art does not have any understanding that not all glycosaminoglycan is removed.
4) Even when comparing the effects of Claim 1 and the prior art, as shown in the following descriptions of the specification, in the case where only some of albumin and glycosaminoglycan are removed in the course of acellularization as recited in Claim 1, the original bonding and the 3D structure of ECM are retained, whereby the structure for cells to move into a tissue repair material and proliferate can be provided.
The biomaterial derived by the methods illustrated above retains the original bonding and the 3D structure of the fish scales, and therefore, it has a high mechanic strength, low possibility of contracting terrestrial contagious diseases and is applicable to repair tissue or tissue implants (paragraph [0018] of the specification). During the step of acellularizing the fish scales, only most of the albumin and few glycosaminoglycans are removed, and collagen, elastin and most of the glycosaminoglycans remains in the extracellular matrix of the original structure. Therefore, the acellularized biomaterial can supply the structure for cells to move in and has good biocompatibility (paragraph [0042] of the specification).
In contrast, the prior art just discloses the formation of pores in a collagen sheet through partial decalcification with the HCl solution as the effects, but fails to recognize or consider the usefulness of the entire structure of fish scales.
In addition, when a high concentration of HCl solution which renders the fish scales into a paste is used, as shown in Table 1 of the prior art, it is unavoidable that the original bonding and the 3D structure of fish scales is completely destroyed or at least partially destroyed whereby the structural strength is decreased.
D. Opinion on Other Arguments by the Defendant
1)With respect to the acellularization of biomaterials, the Defendant submitted Defendant's Exhibit 116) and argued that HCl had been used as an acellularizing agent before the filing date of the application and most glycosaminoglycans are retained with the use of per acetic acid, a kind of acid, and accordingly, Claim 1 would have been easily conceived by combining the above well-known facts with the prior art.7)
2)However, in an action to revoke the IPTAB decision dismissing an appeal against a final rejection, the commissioner of KIPO is not supposed to raise a new rejection ground to which an opportunity to file a response was not given during an examination or trial proceedings.
3)For the present case, considering statements in Plaintiff's Exhibit 4 and 5 along with the purport of the overall argument, the KIPO examiner issued a Notice of Preliminary Rejection on February 27, 2015, on the grounds that “it is disclosed in the prior art that fish scales are dissolved with HCl for 24 hours and grinded with a mixer. In addition, since the grounded product was derived from fish scales as in the application at issue, it is evident that it comprises a mixture of matrix and powder. Thus, Claim 1 would have been easily conceived by a skilled person in the art from the prior art.” In response, the Plaintiff filed a response arguing that “the step of treating HCl in the prior art is for decalcification and the acellularization of the application differs from the decalcification in terms of objective and content.” On July 17, 2015, the KIPO examiner issued a Final Rejection on the grounds that “while the acellularization of the application is not directly disclosed in the prior art, it is evident that fish scales are subject to acellularization as well as decalcification through the step of treating fish scales with HCl. In addition, the effects of the application of retaining collagen, elastin, etc. in extracellular matrix through acellularization to provide superior biocompatibility is not different from providing the biocompatible collagen sheet through HCl treatment in the prior art.” There is no evidence confirming that another Notice of Preliminary Rejection was issued at the IPTAB proceedings. Under the circumstances, the rejection grounds to which an opportunity to file a response was given by the KIPO examiner stated that “fish scales may be subject to acellularization as well as decalcification through the step of treating fish scales with a high concentration of HCl solution in the prior art.” However, Defendant's Exhibit 11 relates to “acellularization” per se by a HCl solution, which cannot be regarded as being the same as the HCl treatment in the prior art for the reasons discussed above. Thus, it cannot be considered that the main content of Defendant's Exhibit 11 is consistent with the rejection grounds to which an opportunity to file a response was given by the KIPO examiner or simply supplements the already-raised rejection grounds.
4) Therefore, the above arguments of the Defendant cannot be taken as a basis for determining the reasonableness of the IPTAB decision and thus are not accepted.
E. Summary of Analysis
In sum, inventiveness should not be determined in hindsight based on whether a skilled person in the art would easily derive the invention with the presumption that a skilled person in the art knows the technology described in the specification. It is not recognized that a skilled person in the art could have easily conceived of Claim 1 from the prior art, which substantially differs from the present invention with respect to the technical field, objective, constitution, and effects. Thus, inventiveness of Claim 1 is not denied by the prior art.
4. Conclusion
The IPTAB erred in its decision. The Plaintiff’s petition to revoke the IPTAB decision is well grounded and therefore shall be granted.
Presiding Judge Woosoo KIM
Judge Sanghoon
Judge Hosan LEE
1)A host recognizes a homogeneous and heterogeneous cell antigen as a foreign substance, and as a result, tissue inflammation or immune rejection may occur. Acellularizing is a process of removing cells from fish scales to prevent such events.
2)Albumin is a simple protein, which is widely distributed in cells or body fluid. It constitutes a basic material of cells together with globulin, and binds to several substances in blood or maintains the osmotic pressure of blood vessels.
3)Glycosaminoglycan is a polysaccharide, which is present as a form of proteoglycan (a generic name of molecules in which the side chains of glycosaminoglycan is covalently bonded to protein) bonded to protein. It usually exists in the epidermis or connective tissue and is involved in the support or flexibility of tissues. It is known that removing glycosaminoglycan from connective tissue causes the slowdown of movement and bioactivity of cells.
4)Decalcification refers to removing calcium from a hard tissue such as bone or a tissue with calcium deposit.
5)Since 0.1M of HCl solution was added together with pepsin for acellularization, the HCl solution appears to assist the action of pepsin (see “Pepsin based protocols” on page 3, right column of Defendant's Exhibit 12). Accordingly, when only the HCl solution is added for acellularization, there is a possibility that the concentration of the HCl solution gets higher. Nevertheless, 0.1M (i.e., 0.365%) is remarkably lower than the 25% HCl solution. Thus, it does not appear that a high concentration of HCl solution as in the prior art is used for acellularization.
6)Defendant's Exhibit 11 is an article entitled “Decellularization of tissues and organs” published in www.sciencedirect.com on March 7, 2006.
7)Meanwhile, the Defendant presented similar arguments with the submission of Defendant's Exhibit 12. However, Defendant's Exhibit 12 is an article entitled “Systematic Comparison of Protocols for the Preparation of Human Articular Cartilage for Use as Scaffold Material in Cartilage Tissue Engineering” published in “TISSUE ENGINEERING: Part C, Volume 22, Number 12” on December 14, 2016. The article was published after the filing date of the application, and further, it cannot be recognized that an opportunity to file a response was given for the same reasons as Defendant's Exhibit 11. Thus, the article cannot be a basis for determination of the reasonableness of the IPTAB decision.