The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-8 are pending and under consideration.
Priority: This application is a CIP of U.S. Application 16622397, filed December 13, 2019, now abandoned, which is a 371 of PCT/KR2017/007220, filed July 6, 2017, which claims priority to foreign application KR 10-2017-0076098, filed June 15, 2017. A copy of the foreign priority document has been received in the parent U.S. application 16622397 on December 13, 2019, and is not in the English language.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-8 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1, line 3, recites a subjective term in the phrase “high-concentration collagen”. There is no specific definition in the specification as to what is meant by “high-concentration” and/or there is no guidance provided as to how one of skill in the art is to determine what concentration of collagen is considered “high-concentration”. Further clarification and/or correction is requested.
Claim 1 is confusing and lacks internal antecedence. Claim 1 recites the phrase “a collagen is separated therefrom, and high-concentration collagen aseptically loaded”. There is no internal antecedence for “high-concentration” because of the phrase recited prior to this phrase. Furthermore, the phrase “a collagen is separated…” implies that there are several types of collagen present and one of them is separated, which does not appear to be the case. Applicants are requested to clarify what steps are actually being performed to what collagen and what collagen product is being manufactured and/or obtained.
Claims 2-6 are included in this rejection because they are dependent on the above claim and fail to cure its defects.
Claims 7-8 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps and/or elements, such omission amounting to a gap between the steps and/or elements. See MPEP § 2172.01. The omitted steps are: the active steps and elements that are required and/or necessary for carrying out a method for restoring cartilage tissue. It is not clear what or whom is being treated for cartilage restoration and how the treating or treatment is carried out. Further clarification and/or correction is requested.
Further claims 7-8 are method claims. The claims are dependent on claim 1, which is drawn to a different method, i.e. a method of manufacturing collagen. Claim 1 is not drawn to a collagen product. The claims do not appear to be proper dependent claims of claim 1.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-8 are rejected under 35 U.S.C. 103 as being unpatentable over Chang et al. (US 20170334969) in view of Eckmayer et al. (US 20030115677), and evidenced by Kim et al. (2016 Korean J Food Sci An 36(5): 665-670). Chang et al. disclose a method for producing a sterile collagen solution, the method comprising washing pig skin tissue with alcohol and water (paragraph 0071), where the alcohol is 70% ethyl alcohol (paragraph 0046); crushing (or fragmenting) the washed pig skin tissue (paragraphs 0072-0073); placing and mixing the washed pig skin tissue with an acid solution containing pepsin (paragraph 0075-0076); adding sodium chloride at a concentration of 0.5-0.9 M to the collagen solution, stirred and aggregated (paragraph 0077); filtering the collagen by a filtration membrane to remove pepsin, sodium chloride, and other materials (paragraphs 0078-0081); removing microorganisms or sterilizing the collagen by filtering the collagen through a filter having a pore size of 0.22 μm (paragraph 0082); aggregating the collagen by adjusting the pH to approximately 6.0-8.0 and adjusting the temperature to 25-35º C (at least paragraphs 0062, 0084); concentrating the aggregated collagen by centrifugation (at least paragraphs 0085-0086); collecting the filtrate containing a sterile collagen solution, where the sterile collagen solution is provided in a form of an injected product in a pre-filled syringe (paragraphs 0083-0089). Chang et al. do not explicitly teach washing the pig skin tissue with sodium hydroxide.
Eckmayer et al. disclose that in a method of obtaining collagen from pig skins, an alkali pretreatment step, with sodium hydroxide, is able to dissolve the bristles and to soften collagen fiber structure (at least paragraphs 0039, 0062).
Kim et al. is cited for further support to note that in a method of obtaining collagen from animal skin and parts, washing with ethanol and sodium hydroxide removes fat and proteinaceous substances, except for collagen (p. 666).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the references and arrive at the claimed method of manufacturing collagen, the method comprising washing pig skin tissue with ethanol and sodium hydroxide; fragmenting the washed pig skin tissue; mixing the fragmented pig skin tissue with an acid solution containing an enzyme; adding sodium chloride (NaCl) to separate collagen from tissue; filtering through a membrane filter to separate collagen from filtrate materials; sterilizing the separated collagen by filtering through a filter having a pore size of 0.22 μm; aggregating the collagen by adjusting the pH to approximately 6.0-8.0 and adjusting the temperature to 25-35º C; collecting the filtrate containing a sterile collagen solution; providing the sterile collagen solution as a product for injection by filling a sterile syringe with the sterile collagen solution (instant claim 1). The motivation to do so is given by the prior art. Chang et al. disclose a method for producing or manufacturing a sterile collagen solution comprising the steps and features noted above. Chang et al. differ from the claimed method by not explicitly reciting washing with sodium hydroxide. Eckmayer et al. disclose that washing pig skin with sodium hydroxide dissolves the bristles and softens the collagen fiber structure. It is further recognized that washing animal skin and parts with ethanol and sodium hydroxide removes fat and proteinaceous substances, respectively, except for collagen (Kim et al.). Therefore, one of ordinary skill would have reasonable motivation to incorporate a washing step with sodium hydroxide as suggested in Eckmayer et al. with the washing step with ethanol in the method of producing a sterile collagen solution filled in a syringe of Chang et al. One of ordinary skill would have a reasonable expectation of success because washing animal skin and parts in ethanol and sodium hydroxide to remove fat and proteinaceous substances in methods of obtaining collagen from animal skin and parts were known.
Regarding instant claim 2, Chang et al. disclose the ethanol is 70% ethyl alcohol for immersing the tissue for 24 hrs. (at least paragraphs 0046-0047, 0073).
Regarding instant claim 3, Eckmayer et al. disclose 0.3-0.8% sodium hydroxide for processing pork rinds for 1-2 hrs. (paragraph 0062), which reasonably has a pH ~13. For instance, it is known that 0.5 % NaOH is equal to 0.125 M NaOH; (OH-)= 0.125; pOH = - log10(0.125); pOH = 0.9031; since pH + pOH = 14, pH = 14-0.9031 =13.097.
Regarding instant clam 4, Chang et al. disclose the crushed (or fragmented) tissue is mixed with an acidic solution pH 1.5-2.5 with enzyme for 72 hrs. or more (at least paragraph 0075).
Regarding instant claim 5, Chang et al. disclose removing microorganisms or sterilizing the collagen by filtering the collagen through a filter having a pore size of 0.22 μm (paragraph 0082).
Regarding instant claim 6, Chang et al. disclose obtaining high concentrations of collagen in the range 114.6-122.3 mg/mL, which is suitable for use as a material for a medical liquid collagen product having a concentration of 30-60 mg/mL (at least paragraph 0106), which is similar to the concentration range 0.7 to 0.9M. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). In this instance, the prior art discloses final collagen concentrations that are similar to the concentrations recited; therefore, it would have been obvious to arrive at the recited concentration range for a final collagen solution by routine optimization.
Regarding instant claims 7-8, Chang et al. disclose collagen is suitable for bio-tissue and is a biodegradable material and is used for medical materials including tissue repair agents, skin grafts, bone grafts, and cell culture (at least paragraph 0008). Chang et al. disclose the sterilized and concentrated collagen may be provided in the form of a product that may be injected into the body in a manner in which the collagen is mixed with an additive so as to possess the same composition as the saline in the human body while maintaining a liquid phase and is then charged in a pre-filled syringe (at least paragraphs 0088-0089). Therefore, it would have been obvious to one of ordinary skill to arrive at the claimed methods for restoring a cartilage tissue, comprising injecting the sterilized collagen solution in a syringe and needle as suggested in Chang et al. to an application site, including a joint, to restore cartilage tissue. One of ordinary skill would have a reasonable expectation of success because it is disclosed in the prior art that sterile collagen solution can be injected into the body as a medical material for tissue repair.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9-13 of U.S. Patent No. 7781158 (‘158) in view of Chang et al. (supra) and Eckmayer et al. (supra). Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant claims and the ‘158 patent claims are drawn to a method of obtaining a sterile collagen solution.
Claims 9-12 of the ‘158 patent recite a method for separating and sterilizing collagen from an animal tissue (porcine skin) comprising:
washing an animal tissue thoroughly with distilled water and ethanol;
processing the washed skin tissue (i.e., fragmenting);
subjecting the resulting fragmented tissue composition to pepsin treatment in 0.1N HCl solution; and obtaining supernatant of the pepsin treated composition containing collagen;
adding NaCl to the supernatant to resulted in a NaCl concentration of 0.5M to 0.8M NaCl in solution containing collagen;
then sterilizing the collagen solution by filtration using the filter having pore size of 0.22 [Symbol font/0x6D]m (claims 11-12 of the ‘158 patent) followed by concentrating the sterilized collagen solution to obtain (collect) 3-7% concentrated collagen solution; which is the common subject matter of instant claim 1.
Although the ‘158 patent claims do not expressly claim the use of sodium hydroxide with ethanol during washing the skin tissue, the relative art (Eckmayer et al.) discloses that porcine skin treated with sodium hydroxide dissolves bristles of the porcine skin and softens collagen fiber structure (see above). Thus, it would have been prima facie obvious for one skilled in the art to treat the collagen-containing skin tissue with sodium hydroxide after its wash with ethanol (‘158 claim 9) to soften and open-up collagen structure to allow the subsequent enzymatic treatment (‘158 claim 9) by pepsin to more efficiently remove the terminus of collagen which cause immune response in human body without affecting the triple-helix structure of collagen (as taught by Chang et al. at [0050]) and to further incorporate the collagen in a prefilled syringe as also suggested in Chang et al. (see 103 above) with a reasonable expectation of success.
Chang et al. disclose that the method comprising aggregating collagen, dissolving the aggregated collagen in purified water to give a collagen solution (see abstract of Chang et al.), and at [0062], Chang et al. disclose the aggregation of collagen depends on the pH (claim 1) of the solution containing collagen (see [0062], Chang et al.). Next, Chang et al. disclose concentrating the aggregated collagen (claim 1) (see ref claim 5 of Chang et al.).
Additionally, Chang et al. provide the teachings that the concentration of ethanol used is 70% (instant claim 2) (see [0046]-[0047], and ref claim 2 of Chang et al.) and that the acidic solution (e.g, phosphoric acid) for the pepsin treatment has pH of 1.5 to 2.5 (instant claim 4) (see [0049], Chang et al.). Eckmayer et al. has taught that 0.3-0.8% NaOH (for 1-2 hours) is used for opening-up collagen structure (see [0062] of Eckmayer et al. and also see above corresponding discussion); it has been known that the 0.5% sodium hydroxide has pH ~13 (instant claim 3) (see the above corresponding discussion in the 103 rejection). It would have been obvious for one skilled in the art to determine and use NaOH solution such as 0.5 % NaOH to obtain a desired result of opening-up collagen structure as taught by Eckmayer et al. with a reasonable expectation of success.
Further, if any steps and/or elements of the instant claims are not expressly recited in the ‘158 patent claims, it would have been obvious to incorporate the noted steps and/or elements in view of the teachings of Chang et al. and/or Eckmayer et al. noted above.
Thus, the instant claims and the claims of the ‘158 patent discussed above are not patentably distinct from each other.
Claims 1-6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 11292827 (‘827) (previously cited as U.S. Application 15527500 (‘500)) in view of Chang et al. (supra) and Eckmayer et al. (supra). Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant claims and the ’827 patent claims are drawn to a method of obtaining a sterile collagen solution.
Claims 1-3 of the ’827 patent recite a method of producing high-concentration and sterile collagen for use as a medical material comprising the steps:
washing tissue of a mammal;
fragmenting by crushing the washed tissue and immersing the crushed tissue in 70% ethyl alcohol (ethanol);
subjecting the tissue to enzymatic treatment by pepsin in purified water titrated to a pH of 1.5 - 2.5 using phosphoric acid, thereby inactivating viruses and extracting collagen;
adding sodium chloride to the extracted collagen at a concentration of 0.5 - 0.9 M to aggregate collagen;
(d) dissolving the aggregated collagen in purified water to give a collagen solution, filtering using a filtration membrane having a pore size of 0.22 [Symbol font/0x6D]m (claims 1-3 of the ’827 patent) and to produce concentrated collagen solution; and then subjecting the collagen concentrated using the tangential flow filtration device to sterile filtration, aggregating the collagen by adjusting pH to 6.0 - 8.0 in a neutralization tank; and
further concentrating collagen to obtain (collect) high-concentration of collagen of 120 mg/ml. Since the method involves inactivating viruses and uses the sterile filtration the concentrated collage is sterilized.
Although the ’827 patent claims do not expressly recite using sodium hydroxide with ethanol during washing/fragmenting of the tissue that is pig tissue recite in instant claim 1, the relative art (Eckmayer et al.) discloses that porcine skin treated with sodium hydroxide dissolves bristles of the porcine skin and softens collagen fiber structure (see above). Eckmayer et al. has taught that 0.3-0.8% NaOH (for 1-2 hours) or 1-1.5 % NaOH (is used for opening-up collagen structure (see [0062] of Eckmayer et al. and also see above corresponding discussion); it has been known that the 0.5% sodium hydroxide has pH ~13 (claim 3) (see the above corresponding discussion in the 103 rejection). It would have been obvious for one skilled in the art to determine and use NaOH solution such as 0.5 % NaOH to obtain a desired result of opening-up collagen structure as taught by Eckmayer et al. with reasonable expectation of success.
Chang et al. further disclose collecting the filtrate containing a sterile collagen solution, where the sterile collagen solution is provided in a form of an injected product in a pre-filled syringe (paragraphs 0083-0089).
Thus, it would have been prima facie obvious for one skilled in the art to treat the collagen-containing skin tissue with sodium hydroxide after washing/fragmenting the tissue with ethanol (as recited in the ’827 patent claims) to soften and open-up collagen structure to allow the subsequent enzymatic treatment (as recited in the ’827 patent claims) and to further incorporate the collagen in a prefilled syringe as also suggested in Chang et al. with a reasonable expectation of success.
Thus, claims 1-3 of the ’827 patent disclose the common subject matters of instant claims 1-6.
Chang et al. disclose that the method comprising aggregating collagen, dissolving the aggregated collagen in purified water to give a collagen solution (see abstract of Chang et al.), and at [0062], Chang et al. disclose the aggregation of collagen depends on the pH (claim 1) of the solution containing collagen (see [0062], Chang et al.). Next, Chang et al. disclose concentrating the aggregated collagen (claim 1) (see ref claim 5 of Chang et al.).
Further, if any steps and/or elements of the instant claims are not expressly recited in the ‘158 patent claims, it would have been obvious to incorporate the noted steps and/or elements in view of the teachings of Chang et al. and/or Eckmayer et al. noted above.
No claim is allowed.
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/Marsha Tsay/Primary Examiner, Art Unit 1656