DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-21 are currently pending and have been examined on their merits.
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 16 and 20-21 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.
Regarding claim 16, the claim recites “wherein the room temperature is about 19˚C, 20˚C, 21˚C, 22˚C, 23˚C, 24˚C, 25˚C, 26˚C, or about 26˚C”. It is unclear if reciting the temperature 26˚C twice is a typo and Applicant intended to include 27˚C or if Applicant intended to include both “26˚C” and “about 26˚C”. Thus, the metes and bounds of claim 16 is unclear and indefinite.
For examination purposes the claim is interpreted as requiring wherein room temperature is about 19˚C, 20˚C, 21˚C, 22˚C, 23˚C, 24˚C, 25˚C, or 26˚C.
Regarding claim 20, the claim recites the limitation "said medium" in line 3. There is insufficient antecedent basis for this limitation in the claim as it is an independent claim and there is no prior recitation of a medium. Thus, the metes and bounds of claim 20 is unclear and indefinite.
For examination purposes the claim is interpreted as requiring “a medium”.
Because claim 21 depends on indefinite claim 20 and does not clarify the point of confusion, this claim must also be rejected under 35 U.S.C. 112, second paragraph.
Appropriate correction is required.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-21 are rejected under 35 U.S.C. 103 as being unpatentable over Cook et al (US 10,039,277-from IDS filed 05/22/2025) in view of Campbell et al (The American Journal of Sports Medicine 2014, from IDS filed 05/22/2025).
Regarding claims 1, 19 and 20, Cook disclose a method of osteochondral tissue preservation comprising storing the tissue at room temperature in a container comprising a serum-free culture medium comprising dexamethasone for from about 7 days to about 70 days prior to implantation, wherein at least 70% of the cells of the tissue remain viable after storing compared to the viability of the cells of the tissue at day 0 (column 22 claim 1).
Cook do not specifically include a step for contacting the osteochondral tissue with chlorhexidine prior to storing the tissue.
Campbell disclose a scientific protocol for sterilizing osteochondral fragments that does not adversely affect cartilage viability by using pulse lavage with 0.002% chlorhexidine (CHG) on osteochondral tissue prior to culturing the cells intended to be further used as allografts (abstract). Accidental osteochondral graft contamination, such as mishandling in the operating room, remains a concern (page 973, column 2). Chlorhexidine has been shown to be a valuable agent for bacterial decontamination (page 974 column 1). The pulse lavage with CHG was applied for 1 minute prior to culture (page 975 column 1) and shown to not have any CFUs (bacterial contamination) after treatment with 0.002% CHG (page 976 column 2).
One of ordinary skill in the art would have been motivated to treat (contact) the osteochondral tissue of Cook with chlorhexidine prior to storing the tissue because Campbell teach and suggest that pretreating osteochondral tissue with chlorhexidine provides the benefit of providing antimicrobial effects with minimal cartilage toxicity and a sterile tissue suitable for use as an allograft. One of ordinary skill in the art would have had a reasonable expectation of success because Campbell disclose the preferred CHG concentration, 0.002%, that provides the optimal results with cell viability and decontamination and Cook also includes a lavage step prior to storing of the tissue (column 23 claim 14).
Regarding claims 2, 11 and 21, Cook disclose wherein the osteochondral tissue is from a section (fragment) humerus, radius, ulna, femur, tibia, spine, scapula, pelvis, patella, talus, phalanges or temporomandibular joint (cartilage or other component of a joint or bone tissue fragment) (column 23 claim 13).
Regarding claims 3-5, Cook disclose testing the osteochondral tissue for viability at least once prior to implantation in a patient, wherein testing for viability comprises assaying the medium withdrawn from said container, wherein testing for viability comprises adding a resazurin solution to the medium and determining the fluorescence level, wherein increased fluorescence indicates higher cell viability (column 22 claims 2-4).
Regarding claims 6-7, Cook disclose changing said medium at least once during the storing and changing the medium about once every two weeks during the storing (column 22, claims 6-7).
Regarding claims 8-10, Cook disclose wherein the medium comprises Dulbecco's Modified Eagle Medium (DMEM), insulin, transferrin, selenium (selenous acid), at least a first antibiotic compound, at least a first antimycotic compound, L-glutamine, non-essential amino acids, ascorbic acid (ascorbate 2-phosphate), and dexamethasone, wherein the at least a first antibiotic compound comprises penicillin and streptomycin, wherein the at least a first antimycotic compound is amphotericin B (column 17 example 5, column 19 example 6, column 22, claim 8).
Regarding claims 12-13, Cook disclose that their method is used with tissue or allograft sources (column 4 lines 1-39). Cook state that although their description may refer to allograft tissue that one of skill in the art appreciates that other tissues find use in their method (column 4 lines 36-39). Cook also includes a lavage step prior to storing of the tissue (column 4, lines 13-14, column 23 claim 14).
Campbell disclose that their treatment of osteochondral tissue with chlorhexidine (CHG), can be performed with an autograft transfer system technique (page 974 column 2, page 975 Figure 1).
One of ordinary skill in the art would have been motivated with a reasonable expectation of success to include autograft tissue as well as allograft tissue in the method of Cook because Cook indicate that their method can be used with other types of tissues and Campbell indicates that chlorhexidine can be used with an autograft transfer system technique.
Regarding claim 14, Cook disclose further comprising implanting the tissue in a subject in need thereof following said storing (column 23 claim 15).
Regarding claims 15-16, Cook disclose wherein the room temperature is between about 19°C and 27°C, and wherein the room temperature is about 19°C, 20°C, 21°C, 22°C, 23°C, 24°C, 25°C, 26°C, or about 26°C (column 4, lines 44-47).
Regarding claims 17-18, Campbell disclose that the CHG exposure to at least 1 minute pulse lavage (page 975).
However, one of ordinary skill in the art would have been motivated to optimize the time of CHG exposure and increase the time period to 5 minutes or 20 minutes to increase the likelihood of complete decontamination, especially in cases where the tissue was accidently dropped on the operating room floor during harvest, which Campbell indicates is a possibility and concern (page 973 column 2). One of ordinary skill in the art would have had a reasonable expectation of success because Campbell disclose a very low concentration of CHG can decontaminate tissue and still provide high cell viability.
Therefore, the combined teachings of Cook et al and Campbell et al render obvious Applicant’s invention as claimed.
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 1-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 19/604370 in view of Cook et al (US 10,039,277-from IDS filed 05/22/2025) and Campbell et al (The American Journal of Sports Medicine 2014, from IDS filed 05/22/2025).
The copending claims of Application ‘370 are drawn to a method of preserving peripheral nerve tissue comprising storing the tissue at room temperature in a container comprising a serum-free culture medium comprising dexamethasone for from about 7 days to about 70 days prior to implantation, wherein at least 70% of the cells of the tissue remain viable after storing compared to the viability of the cells of the tissue at day 0.
The copending claims also include testing the withdrawn medium for viability with resazurin, changing the medium at least once during storing and once every two weeks during storing, wherein the medium comprises DMEM, insulin, transferrin, selenium, antibiotic such as penicillin/streptomycin, antimycotic such as amphotericin B, L-glutamine, non-essential amino acids, ascorbic acid, and dexamethasone, an autograft or allograft, lavaging in isotonic solution prior to storing, further implanting the tissue in a subject in need following storing and wherein the room temperature is between 19˚C and 27˚C.
The copending claims do not specifically disclose their method with osteochondral tissue.
Cook disclose a method of tissue preservation comprising storing the tissue at room temperature in a container comprising a serum-free culture medium comprising dexamethasone for from about 7 days to about 70 days prior to implantation, wherein at least 70% of the cells of the tissue remain viable after storing compared to the viability of the cells of the tissue at day 0 (column 22 claim 1). Cook disclose that the tissue source may include tissues of the eye, brain, osteochondral or any tissue source that may require transplantation (column 4 lines 23-39).
One of ordinary skill in the art would have been motivated with a reasonable expectation of success to use osteochondral tissue, such as cartilage and bone fragments, or from tissue of the spine or other bones or joints, in the method of the ‘370 copending claims because Cook teach and suggest that this method of tissue preservation is suitable for osteochondral tissue as well as other types of tissue, such as eye and brain tissue which also contain nerve tissue.
Neither the copending claims nor Cook specifically include a step for contacting an osteochondral tissue with chlorhexidine prior to storing the tissue.
Campbell disclose a scientific protocol for sterilizing osteochondral fragments that does not adversely affect cartilage viability by using pulse lavage with 0.002% chlorhexidine (CHG) on osteochondral tissue prior to culturing the cells intended to be further used as allografts (abstract). Accidental osteochondral graft contamination, such as mishandling in the operating room, remains a concern (page 973, column 2). Chlorhexidine has been shown to be a valuable agent for bacterial decontamination (page 974 column 1). The pulse lavage with CHG was applied for 1 minute prior to culture (page 975 column 1) and shown to not have any CFUs (bacterial contamination) after treatment with 0.002% CHG (page 976 column 2).
One of ordinary skill in the art would have been motivated to treat (contact) osteochondral tissue in the method of the copending claims, as modified by Cook, with chlorhexidine prior to storing the tissue because Campbell teach and suggest that pretreating osteochondral tissue with chlorhexidine provides the benefit of providing antimicrobial effects with minimal cartilage toxicity and a sterile tissue suitable for use as an allograft. One of ordinary skill in the art would have been motivated to optimize the time of contact with the chlorhexidine to about 5 minutes or 20 minutes in order to ensure the decontamination is complete because Campbell indicate that the dropping of tissue on the floor is a real concern. One of ordinary skill in the art would have had a reasonable expectation of success because Campbell disclose the preferred CHG concentration, 0.002%, that provides the optimal results with cell viability and decontamination and Cook also includes a lavage step prior to storing of the tissue (column 23 claim 14).
Therefore, the combined teachings of the copending claims ‘370, Cook et al and Campbell et al render obvious the current claims.
This is a provisional nonstatutory double patenting rejection.
Claims 1-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 9,220,258 in view of Cook et al (US 10,039,277-from IDS filed 05/22/2025) and Campbell et al (The American Journal of Sports Medicine 2014, from IDS filed 05/22/2025).
The claims of patent ‘258 are drawn to a method of osteochondral tissue preservation comprising storing the tissue at room temperature in a container comprising a serum-free culture medium comprising dexamethasone for from about 63 days to about 75 days prior to implantation, wherein at least 70% of the cells of the tissue remain viable after storing compared to the viability of the cells of the tissue at day 0.
The claims of patent ‘258 further include testing the withdrawn medium for viability with resazurin, changing the medium at least once during storing and once every two weeks during storing, wherein the medium comprises DMEM, insulin, transferrin, selenium, antibiotic, antimycotic, non-essential amino acids, ascorbate 2-phosphate (ascorbic acid), and dexamethasone, an allograft, lavaging in isotonic solution prior to storing, further implanting the tissue in a subject in need following storing and wherein the room temperature is between 19˚C and 27˚C.
The claims of the patent ‘258 do not specifically include wherein the storing is for 7 to 70 days (although the range of 63-75 days overlaps and thus renders obvious the claimed range) or wherein the medium comprises an antibiotic such as penicillin/streptomycin, antimycotic such as amphotericin B, L-glutamine, non-essential amino acids, or wherein the tissue comprises an autograft, however these are well known in the prior art as suitable and beneficial for inclusion in such a method as taught and suggested by Cook ‘277.
Cook disclose a method of osteochondral tissue preservation comprising storing the tissue at room temperature in a container comprising a serum-free culture medium comprising dexamethasone for from about 7 days to about 70 days prior to implantation, wherein at least 70% of the cells of the tissue remain viable after storing compared to the viability of the cells of the tissue at day 0.
Cook disclose wherein the medium comprises Dulbecco's Modified Eagle Medium (DMEM), insulin, transferrin, selenium (selenous acid), at least a first antibiotic compound, at least a first antimycotic compound, L-glutamine, non-essential amino acids, ascorbic acid (ascorbate 2-phosphate), and dexamethasone, wherein the at least a first antibiotic compound comprises penicillin and streptomycin, wherein the at least a first antimycotic compound is amphotericin B (column 17 example 5, column 19 example 6, column 22, claim 8).
Neither the patent claims nor Cook specifically include a step for contacting an osteochondral tissue with chlorhexidine prior to storing the tissue.
Campbell disclose a scientific protocol for sterilizing osteochondral fragments that does not adversely affect cartilage viability by using pulse lavage with 0.002% chlorhexidine (CHG) on osteochondral tissue prior to culturing the cells intended to be further used as allografts (abstract). Accidental osteochondral graft contamination, such as mishandling in the operating room, remains a concern (page 973, column 2). Chlorhexidine has been shown to be a valuable agent for bacterial decontamination (page 974 column 1). The pulse lavage with CHG was applied for 1 minute prior to culture (page 975 column 1) and shown to not have any CFUs (bacterial contamination) after treatment with 0.002% CHG (page 976 column 2).
One of ordinary skill in the art would have been motivated to treat (contact) osteochondral tissue in the method of the patent claims, as modified by Cook, with chlorhexidine prior to storing the tissue because Campbell teach and suggest that pretreating osteochondral tissue with chlorhexidine provides the benefit of providing antimicrobial effects with minimal cartilage toxicity and a sterile tissue suitable for use as an allograft. One of ordinary skill in the art would have been motivated to optimize the time of contact with the chlorhexidine to about 5 minutes or 20 minutes in order to ensure the decontamination is complete because Campbell indicate that the dropping of tissue on the floor is a real concern. One of ordinary skill in the art would have had a reasonable expectation of success because Campbell disclose the preferred CHG concentration, 0.002%, that provides the optimal results with cell viability and decontamination and Cook also includes a lavage step prior to storing of the tissue (column 23 claim 14).
Cook disclose that their method is used with tissue or allograft sources (column 4 lines 1-39). Cook state that although their description may refer to allograft tissue that one of skill in the art appreciates that other tissues find use in their method (column 4 lines 36-39). Cook also includes a lavage step prior to storing of the tissue (column 4, lines 13-14, column 23 claim 14).
Campbell disclose that their treatment of osteochondral tissue with chlorhexidine (CHG), can be performed with an autograft transfer system technique (page 974 column 2, page 975 Figure 1).
One of ordinary skill in the art would have been motivated with a reasonable expectation of success to include autograft tissue as well as allograft tissue in the method of Cook because Cook indicate that their method can be used with other types of tissues and Campbell indicates that chlorhexidine can be used with an autograft transfer system technique.
Therefore, the combined teachings of the patent claims ‘258, Cook et al and Campbell et al render obvious the current claims.
Claims 1-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 10,039,277 in view of Cook et al (US 9,220,258-from IDS filed 05/22/2025) and Campbell et al (The American Journal of Sports Medicine 2014, from IDS filed 05/22/2025).
The claims of patent ‘277 are drawn to a method of osteochondral tissue preservation comprising storing the tissue at room temperature in a container comprising a serum-free culture medium comprising dexamethasone for from about 7 days to about 70 days prior to implantation, wherein at least 70% of the cells of the tissue remain viable after storing compared to the viability of the cells of the tissue at day 0 (claim 1).
The patent claims include wherein the osteochondral tissue is from a section (fragment) humerus, radius, ulna, femur, tibia, spine, scapula, pelvis, patella, talus, phalanges or temporomandibular joint (cartilage or other component of a joint or bone tissue fragment) (claim 13). The patent claims include testing the osteochondral tissue for viability at least once prior to implantation in a patient, wherein testing for viability comprises assaying the medium withdrawn from said container, wherein testing for viability comprises adding a resazurin solution to the medium and determining the fluorescence level, wherein increased fluorescence indicates higher cell viability (claims 2-4). The patent claims include changing said medium at least once during the storing and changing the medium about once every two weeks during the storing (claims 6-7).
The patent claims include further comprising implanting the tissue in a subject in need thereof following said storing (column 23 claim 15).
The claims of the patent ‘098 do not specifically include wherein the room temperature is between 19˚C and 27˚C (however room temperature is generally understood in the art to be around 20-22˚C and thus obvious) or wherein the medium comprises an antibiotic such as penicillin/streptomycin, antimycotic such as amphotericin B, L-glutamine, non-essential amino acids, or wherein the tissue comprises an autograft, however these are well known in the prior art as suitable and beneficial for inclusion in such a method of osteochondral preservation as taught and suggested by Cook ‘258 and thus obvious additions to the patent claimed method.
Cook ‘258 disclose wherein the medium comprises Dulbecco's Modified Eagle Medium (DMEM), insulin, transferrin, selenium (selenous acid), at least a first antibiotic compound, at least a first antimycotic compound, L-glutamine, non-essential amino acids, ascorbic acid (ascorbate 2-phosphate), and dexamethasone, wherein the at least a first antibiotic compound comprises penicillin and streptomycin, wherein the at least a first antimycotic compound is amphotericin B (column 17 example 5, column 19 example 6, column 22). Cook ‘258 disclose wherein the room temperature is between about 19°C and 27°C, and wherein the room temperature is about 19°C, 20°C, 21°C, 22°C, 23°C, 24°C, 25°C, 26°C, or about 26°C (column 4, lines 37-40).
Patent ‘277 do not specifically include a step for contacting the osteochondral tissue with chlorhexidine prior to storing the tissue.
Campbell disclose a scientific protocol for sterilizing osteochondral fragments that does not adversely affect cartilage viability by using pulse lavage with 0.002% chlorhexidine (CHG) on osteochondral tissue prior to culturing the cells intended to be further used as allografts (abstract). Accidental osteochondral graft contamination, such as mishandling in the operating room, remains a concern (page 973, column 2). Chlorhexidine has been shown to be a valuable agent for bacterial decontamination (page 974 column 1). The pulse lavage with CHG was applied for 1 minute prior to culture (page 975 column 1) and shown to not have any CFUs (bacterial contamination) after treatment with 0.002% CHG (page 976 column 2).
One of ordinary skill in the art would have been motivated to treat (contact) the osteochondral tissue of the patent claims with chlorhexidine prior to storing the tissue because Campbell teach and suggest that pretreating osteochondral tissue with chlorhexidine provides the benefit of providing antimicrobial effects with minimal cartilage toxicity and a sterile tissue suitable for use as an allograft. One of ordinary skill in the art would have been motivated to optimize the time of contact with the chlorhexidine to about 5 minutes or 20 minutes in order to ensure the decontamination is complete because Campbell indicate that the dropping of tissue on the floor is a real concern. One of ordinary skill in the art would have had a reasonable expectation of success because Campbell disclose the preferred CHG concentration, 0.002%, that provides the optimal results with cell viability and decontamination and Cook also includes a lavage step prior to storing of the tissue (column 23 claim 14).
One of ordinary skill in the art would have been motivated to optimize the time of CHG exposure and increase the time period to 5 minutes or 20 minutes to increase the likelihood of complete decontamination, especially in cases where the tissue was accidently dropped on the operating room floor during harvest, which Campbell indicates is a possibility and concern (page 973 column 2). One of ordinary skill in the art would have had a reasonable expectation of success because Campbell disclose a very low concentration of CHG can decontaminate tissue and still provide high cell viability.
The patent claims do not specifically include wherein the tissue is an autograft.
Cook ‘258 disclose that their osteochondral preservation method is used with tissue or allograft sources (column 4 lines 1-39). Cook state that although their description may refer to allograft tissue that one of skill in the art appreciates that other tissues find use in their method (column 4 lines 36-39). Cook also includes a lavage step prior to storing of the tissue (column 4, lines 13-14, column 23 claim 14).
Campbell disclose that their treatment of osteochondral tissue with chlorhexidine (CHG), can be performed with an autograft transfer system technique (page 974 column 2, page 975 Figure 1).
One of ordinary skill in the art would have been motivated with a reasonable expectation of success to include autograft tissue as well as allograft tissue in the patent method because Cook indicate that their method can be used with other types of tissues and Campbell indicates that chlorhexidine can be used with an autograft transfer system technique.
Therefore, the combined teachings of patent ‘277, Cook et al and Campbell et al render obvious Applicant’s invention as claimed.
Claims 1-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 10,881,098 in view of Cook et al (10,039,277-from IDS filed 05/22/2025) and Campbell et al (The American Journal of Sports Medicine 2014, from IDS filed 05/22/2025).
The claims of patent ‘098 are drawn to a method of meniscus (osteochondral) tissue preservation comprising storing the tissue at room temperature in a container comprising a serum-free culture medium comprising dexamethasone for from about 7 days to about 70 days prior to implantation, wherein at least 70% of the cells of the tissue remain viable after storing compared to the viability of the cells of the tissue at day 0.
The claims of patent ‘098 further include testing the withdrawn medium for viability with resazurin, changing the medium at least once during storing and once every two weeks during storing, wherein the medium comprises DMEM, insulin, transferrin, selenium, antibiotic, antimycotic, non-essential amino acids, ascorbate 2-phosphate (ascorbic acid), and dexamethasone, an allograft, lavaging in isotonic solution prior to storing, further implanting the tissue in a subject in need following storing and wherein the room temperature is between 19˚C and 27˚C.
The claims of the patent ‘098 do not specifically include wherein the room temperature is between 19˚C and 27˚C (however room temperature is generally understood in the art to be around 20-22˚C and thus obvious) or wherein the medium comprises an antibiotic such as penicillin/streptomycin, antimycotic such as amphotericin B, L-glutamine, non-essential amino acids, or wherein the tissue comprises an autograft, however these are well known in the prior art as suitable and beneficial for inclusion in such a method as taught and suggested by Cook ‘277.
Cook disclose a method of osteochondral tissue preservation comprising storing the tissue at room temperature in a container comprising a serum-free culture medium comprising dexamethasone for from about 7 days to about 70 days prior to implantation, wherein at least 70% of the cells of the tissue remain viable after storing compared to the viability of the cells of the tissue at day 0.
Cook disclose wherein the medium comprises Dulbecco's Modified Eagle Medium (DMEM), insulin, transferrin, selenium (selenous acid), at least a first antibiotic compound, at least a first antimycotic compound, L-glutamine, non-essential amino acids, ascorbic acid (ascorbate 2-phosphate), and dexamethasone, wherein the at least a first antibiotic compound comprises penicillin and streptomycin, wherein the at least a first antimycotic compound is amphotericin B (column 17 example 5, column 19 example 6, column 22, claim 8).
Neither the patent claims nor Cook specifically include a step for contacting an osteochondral tissue with chlorhexidine prior to storing the tissue.
Campbell disclose a scientific protocol for sterilizing osteochondral fragments that does not adversely affect cartilage viability by using pulse lavage with 0.002% chlorhexidine (CHG) on osteochondral tissue prior to culturing the cells intended to be further used as allografts (abstract). Accidental osteochondral graft contamination, such as mishandling in the operating room, remains a concern (page 973, column 2). Chlorhexidine has been shown to be a valuable agent for bacterial decontamination (page 974 column 1). The pulse lavage with CHG was applied for 1 minute prior to culture (page 975 column 1) and shown to not have any CFUs (bacterial contamination) after treatment with 0.002% CHG (page 976 column 2).
One of ordinary skill in the art would have been motivated to treat (contact) osteochondral tissue in the method of the patent claims, as modified by Cook, with chlorhexidine prior to storing the tissue because Campbell teach and suggest that pretreating osteochondral tissue with chlorhexidine provides the benefit of providing antimicrobial effects with minimal cartilage toxicity and a sterile tissue suitable for use as an allograft. One of ordinary skill in the art would have been motivated to optimize the time of contact with the chlorhexidine to about 5 minutes or 20 minutes in order to ensure the decontamination is complete because Campbell indicate that the dropping of tissue on the floor is a real concern. One of ordinary skill in the art would have had a reasonable expectation of success because Campbell disclose the preferred CHG concentration, 0.002%, that provides the optimal results with cell viability and decontamination and Cook also includes a lavage step prior to storing of the tissue (column 23 claim 14).
Cook disclose that their method is used with tissue or allograft sources (column 4 lines 1-39). Cook state that although their description may refer to allograft tissue that one of skill in the art appreciates that other tissues find use in their method (column 4 lines 36-39). Cook also includes a lavage step prior to storing of the tissue (column 4, lines 13-14, column 23 claim 14).
Campbell disclose that their treatment of osteochondral tissue with chlorhexidine (CHG), can be performed with an autograft transfer system technique (page 974 column 2, page 975 Figure 1).
One of ordinary skill in the art would have been motivated with a reasonable expectation of success to include autograft tissue as well as allograft tissue in the method of the patent claims because Cook indicate that their method can be used with other types of tissues and Campbell indicates that chlorhexidine can be used with an autograft transfer system technique.
Therefore, the combined teachings of the patent claims ‘098, Cook et al and Campbell et al render obvious the current claims.
Claims 1-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 11,503,823 in view of Cook et al (10,039,277-from IDS filed 05/22/2025) and Campbell et al (The American Journal of Sports Medicine 2014, from IDS filed 05/22/2025).
The claims of patent ‘823 are drawn to a method of ligament (osteochondral) tissue preservation comprising storing the tissue at room temperature in a container comprising a serum-free culture medium comprising dexamethasone for from about 7 days to about 70 days prior to implantation, wherein at least 70% of the cells of the tissue remain viable after storing compared to the viability of the cells of the tissue at day 0.
The claims of patent ‘823 further include testing the withdrawn medium for viability with resazurin, changing the medium at least once during storing and once every two weeks during storing, wherein the medium comprises DMEM, insulin, transferrin, selenium, antibiotic, antimycotic, non-essential amino acids, ascorbate 2-phosphate (ascorbic acid), and dexamethasone, an allograft, lavaging in isotonic solution prior to storing, further implanting the tissue in a subject in need following storing and wherein the room temperature is between 19˚C and 27˚C.
The claims of the patent ‘823 do not specifically include wherein the room temperature is between 19˚C and 27˚C (however room temperature is generally understood in the art to be around 20-22˚C and thus obvious) or wherein the medium comprises an antibiotic such as penicillin/streptomycin, antimycotic such as amphotericin B, L-glutamine, non-essential amino acids, or wherein the tissue comprises an autograft, however these are well known in the prior art as suitable and beneficial for inclusion in such a method as taught and suggested by Cook ‘277.
Cook disclose a method of osteochondral tissue preservation comprising storing the tissue at room temperature in a container comprising a serum-free culture medium comprising dexamethasone for from about 7 days to about 70 days prior to implantation, wherein at least 70% of the cells of the tissue remain viable after storing compared to the viability of the cells of the tissue at day 0.
Cook disclose wherein the medium comprises Dulbecco's Modified Eagle Medium (DMEM), insulin, transferrin, selenium (selenous acid), at least a first antibiotic compound, at least a first antimycotic compound, L-glutamine, non-essential amino acids, ascorbic acid (ascorbate 2-phosphate), and dexamethasone, wherein the at least a first antibiotic compound comprises penicillin and streptomycin, wherein the at least a first antimycotic compound is amphotericin B (column 17 example 5, column 19 example 6, column 22, claim 8).
Neither the patent claims nor Cook specifically include a step for contacting an osteochondral tissue with chlorhexidine prior to storing the tissue.
Campbell disclose a scientific protocol for sterilizing osteochondral fragments that does not adversely affect cartilage viability by using pulse lavage with 0.002% chlorhexidine (CHG) on osteochondral tissue prior to culturing the cells intended to be further used as allografts (abstract). Accidental osteochondral graft contamination, such as mishandling in the operating room, remains a concern (page 973, column 2). Chlorhexidine has been shown to be a valuable agent for bacterial decontamination (page 974 column 1). The pulse lavage with CHG was applied for 1 minute prior to culture (page 975 column 1) and shown to not have any CFUs (bacterial contamination) after treatment with 0.002% CHG (page 976 column 2).
One of ordinary skill in the art would have been motivated to treat (contact) osteochondral tissue in the method of the patent claims, as modified by Cook, with chlorhexidine prior to storing the tissue because Campbell teach and suggest that pretreating osteochondral tissue with chlorhexidine provides the benefit of providing antimicrobial effects with minimal cartilage toxicity and a sterile tissue suitable for use as an allograft. One of ordinary skill in the art would have been motivated to optimize the time of contact with the chlorhexidine to about 5 minutes or 20 minutes in order to ensure the decontamination is complete because Campbell indicate that the dropping of tissue on the floor is a real concern. One of ordinary skill in the art would have had a reasonable expectation of success because Campbell disclose the preferred CHG concentration, 0.002%, that provides the optimal results with cell viability and decontamination and Cook also includes a lavage step prior to storing of the tissue (column 23 claim 14).
Cook disclose that their method is used with tissue or allograft sources (column 4 lines 1-39). Cook state that although their description may refer to allograft tissue that one of skill in the art appreciates that other tissues find use in their method (column 4 lines 36-39). Cook also includes a lavage step prior to storing of the tissue (column 4, lines 13-14, column 23 claim 14).
Campbell disclose that their treatment of osteochondral tissue with chlorhexidine (CHG), can be performed with an autograft transfer system technique (page 974 column 2, page 975 Figure 1).
One of ordinary skill in the art would have been motivated with a reasonable expectation of success to include autograft tissue as well as allograft tissue in the method of the patent claims because Cook indicate that their method can be used with other types of tissues and Campbell indicates that chlorhexidine can be used with an autograft transfer system technique.
Therefore, the combined teachings of the patent claims ‘823, Cook et al and Campbell et al render obvious the current claims.
Claims 1-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11,864,554 in view of Cook et al (10,039,277-from IDS filed 05/22/2025) and Campbell et al (The American Journal of Sports Medicine 2014, from IDS filed 05/22/2025).
The claims of patent ‘554 are drawn to a method of tendon (osteochondral) tissue preservation comprising storing the tissue at room temperature in a container comprising a serum-free culture medium comprising dexamethasone for from about 7 days to about 70 days prior to implantation, wherein at least 70% of the cells of the tissue remain viable after storing compared to the viability of the cells of the tissue at day 0.
The claims of patent ‘554 further include testing the withdrawn medium for viability with resazurin, changing the medium at least once during storing and once every two weeks during storing, wherein the medium comprises DMEM, insulin, transferrin, selenium, antibiotic, antimycotic, non-essential amino acids, ascorbate 2-phosphate (ascorbic acid), and dexamethasone, an allograft, lavaging in isotonic solution prior to storing, further implanting the tissue in a subject in need following storing and wherein the room temperature is between 19˚C and 27˚C.
The claims of the patent ‘554 do not specifically include wherein the room temperature is between 19˚C and 27˚C (however room temperature is generally understood in the art to be around 20-22˚C and thus obvious) or wherein the medium comprises an antibiotic such as penicillin/streptomycin, antimycotic such as amphotericin B, L-glutamine, non-essential amino acids, or wherein the tissue comprises an autograft, however these are well known in the prior art as suitable and beneficial for inclusion in such a method as taught and suggested by Cook ‘277.
Cook disclose a method of osteochondral tissue preservation comprising storing the tissue at room temperature in a container comprising a serum-free culture medium comprising dexamethasone for from about 7 days to about 70 days prior to implantation, wherein at least 70% of the cells of the tissue remain viable after storing compared to the viability of the cells of the tissue at day 0.
Cook disclose wherein the medium comprises Dulbecco's Modified Eagle Medium (DMEM), insulin, transferrin, selenium (selenous acid), at least a first antibiotic compound, at least a first antimycotic compound, L-glutamine, non-essential amino acids, ascorbic acid (ascorbate 2-phosphate), and dexamethasone, wherein the at least a first antibiotic compound comprises penicillin and streptomycin, wherein the at least a first antimycotic compound is amphotericin B (column 17 example 5, column 19 example 6, column 22, claim 8).
Neither the patent claims nor Cook specifically include a step for contacting an osteochondral tissue with chlorhexidine prior to storing the tissue.
Campbell disclose a scientific protocol for sterilizing osteochondral fragments that does not adversely affect cartilage viability by using pulse lavage with 0.002% chlorhexidine (CHG) on osteochondral tissue prior to culturing the cells intended to be further used as allografts (abstract). Accidental osteochondral graft contamination, such as mishandling in the operating room, remains a concern (page 973, column 2). Chlorhexidine has been shown to be a valuable agent for bacterial decontamination (page 974 column 1). The pulse lavage with CHG was applied for 1 minute prior to culture (page 975 column 1) and shown to not have any CFUs (bacterial contamination) after treatment with 0.002% CHG (page 976 column 2).
One of ordinary skill in the art would have been motivated to treat (contact) osteochondral tissue in the method of the patent claims, as modified by Cook, with chlorhexidine prior to storing the tissue because Campbell teach and suggest that pretreating osteochondral tissue with chlorhexidine provides the benefit of providing antimicrobial effects with minimal cartilage toxicity and a sterile tissue suitable for use as an allograft. One of ordinary skill in the art would have been motivated to optimize the time of contact with the chlorhexidine to about 5 minutes or 20 minutes in order to ensure the decontamination is complete because Campbell indicate that the dropping of tissue on the floor is a real concern. One of ordinary skill in the art would have had a reasonable expectation of success because Campbell disclose the preferred CHG concentration, 0.002%, that provides the optimal results with cell viability and decontamination and Cook also includes a lavage step prior to storing of the tissue (column 23 claim 14).
Cook disclose that their method is used with tissue or allograft sources (column 4 lines 1-39). Cook state that although their description may refer to allograft tissue that one of skill in the art appreciates that other tissues find use in their method (column 4 lines 36-39). Cook also includes a lavage step prior to storing of the tissue (column 4, lines 13-14, column 23 claim 14).
Campbell disclose that their treatment of osteochondral tissue with chlorhexidine (CHG), can be performed with an autograft transfer system technique (page 974 column 2, page 975 Figure 1).
One of ordinary skill in the art would have been motivated with a reasonable expectation of success to include autograft tissue as well as allograft tissue in the method of the patent claims because Cook indicate that their method can be used with other types of tissues and Campbell indicates that chlorhexidine can be used with an autograft transfer system technique.
Therefore, the combined teachings of the patent claims ‘554, Cook et al and Campbell et al render obvious the current claims.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Malinin, Theodore I., “Tissue Allograft Sterilization Method”, US 2018/0264148.
(Malinin disclose the use of chlorhexidine to sterilize bone tissue for transplantation).
Nover et al. “Long-Term Storage and Preservation of Tissue Engineered Articular Cartilage”, Journal Orthopaedic Research, 2016 January ; 34(1): 141–148.
(Nover discloses the use of Missouri Osteochondral Allograft Preservation System (MOPS) for room temperature storage of tissue grafts)
Utkan et al., “What if an articular bone fragment drops on the floor in the course of osteosynthesis? An experimental study”, Joint Diseases and Related Surgery, December 2023, 35(1), pp. 209-217.
(Utkan disclose the use of chlorhexidine for treatment of osteochondral bone fragments with chlorhexidine.)
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LAURA J. SCHUBERG
Primary Examiner
Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631
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