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 .
DETAILED ACTION
Response to Amendment
Status of the Claims
Receipt of Applicant’s response, filed 21 Aug 2025 has been entered.
Claims 1-11, 13-17, 26, 47 and 48 remain pending in the application.
Claims 1, 2, 4, 7-9, 13, and 14 are amended.
Claims 12, 18-25 and 27-46 cancelled.
Claims 47 and 48 are new.
Claims 3, 16, 17 and 26 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention. Claim 3 requires a treatment other than pepsin and elastase.
Claims 1, 2, 4-11, 13-15, 47 and 48 are under consideration to the extent of the elected species, i.e., that the treatment component is pepsin and elastase and that the serum is FBS.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows: in the prior-filed application, Application No. 63/005,762, the applicant failed to provide adequate written description support for claims 1, 2, 4-11, 13-15, 47 and 48. Accordingly, priority cannot be granted at this time, thus claims 1, 2, 4-11, 13-15, 47 and 48 are granted the filing date of PCT/US21/25782 (05 Apr 2021).
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994)
The disclosure of the prior-filed application, Application No. 63/005,762, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Application ‘762 fails to provide support for the intervertebral annulus fibrosis cartilage as in instant claim 1. Accordingly, claims 1, 2, 4-11, 13-15, 47 and 48 are not entitled to the benefit of the prior application.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 21 Aug 2025 is in compliance with the provisions of 37 CFR 1.97, except where noted. Accordingly, the information disclosure statement is being considered by the examiner.
Objections Withdrawn
Objections to the Specification
The specification objections set forth in the Non-Final Office Action mailed 08 May 2025 are hereby withdrawn in light of applicant’s amendments of the specification.
Objections to the Claims
The claim objections of claim 8 and 14 set forth in the Non-Final Office Action mailed 08 May 2025 are hereby withdrawn in light of applicant’s amendments of the claims.
Rejections Withdrawn
Rejections Pursuant to 35 USC § 112
The rejections of claims 1, 2, 4-10 and 13-15 pursuant to 35 U.S.C. 112(b) set forth in the Non-Final Office Action mailed 08 May 2025 are partially withdrawn in light of applicants amendment of the claims.
Objections/Rejections Maintained
Claim Objections
Claim 7 is objected to because of the following informalities:
Claim 7 recites “99% greater” in the second and fourth lines of the claim . This is missing a word such as “or” between “99%” and “greater” which would improve the readability of the claim.
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, 2, 4-10 and 13-15 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 2 is indefinite for the phrase "such as" because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
New Grounds of Objections/Rejections
Claim Objections
Claims 1, 9 and 48 are objected to because of the following informalities:
Claim 1 recites in step (b) “treating said FMC or IAFC an enzyme to remove.” A word such as “with” is missing between “IAFC” and “an enzyme.”
Claim 9 recites “100% devoid glycosaminoglycan.” This is missing a word such as “of” after “devoid.”
Claim 48 appears to be missing “of” between “step (a)” and “is non-human.”
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 9 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The amendment filed 21 Aug 2025 has introduced new matter into the claims. Amended claim 9 recites that the transplant material is 100% devoid glycosaminoglycan and collagen. Original claim 9 recited that the material is 100% glycosaminoglycan and collagen but not that the material was devoid glycosaminoglycan and collagen. The response did not point out where support for newly added limitation that the material is 100% devoid of glycosaminoglycan and collagen could be found in the originally filed disclosure. Although the PTO has the initial burden of presenting evidence or reasons why persons skilled in the art would not recognize in the disclosure a description of the invention defined by the claims, when filing an amendment an applicant should show support in the original disclosure for new or amended claims. See MPEP 714.02 and 2163.06 (“Applicant should therefore specifically point out the support for any amendments made to the disclosure.”). Instant claim 9 now recites limitations, which were not clearly disclosed in the specification as filed, and now change the scope of the instant disclosure as filed. Such limitations recited in newly amended claim 9, which did not appear in the specification, as filed, introduce new concepts and violate the description requirement of the first paragraph of 35 U.S.C 112. Applicant is required to provide sufficient written support for the limitations recited in present claim 9 in the specification or claims, as-filed, or remove these limitations from the claims in response to this Office Action.
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, 2, 4-10, 13-15, 47 and 48 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 recites “an enzyme to remove blood vessels and/or elastin” and further recites that the decellularized material is free of certain percentages of starting elastin content. This confusing because the removal of elastin in step (b) is optional but the ending wherein clause seems to imply that the removal of elastin may be required. It is thus unclear if the claim is intended to require the removal of elastin or if the removal of elastin is optional. Claims 2, 4-10, 13-15, 47 and 48 are included in this rejection as they depend directly, indirectly, or include all the limitations of independent claim 1.
Claim 2 is indefinite for lack of antecedent basis for “one or more enzymes.” Claim 1 recites “an enzyme” but not “one or more enzymes” and it is unclear if the enzymes of clam 2 are the same or different from the enzyme of claim 1.
Claim 9 recites that the material is a certain percentage (at least 30-99%) of glycosaminoglycan and collagen or that it is 100% devoid glycosaminoglycan and collagen. The word “devoid” is not present after the percentages 30-99% and the claim appears to read that the material contains that level of glycosaminoglycan and collagen but this is unclear as the claim additionally recites that the material is 100% devoid of glycosaminoglycan and collagen. It is unclear if the glycosaminoglycan and collagen are intended to be part of the transplant material or absent from the material.
Claim 47 lacks antecedent basis for “the endopeptidase” and for “the cysteine proteinase.”
Claim Rejections - 35 USC § 103
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.
The art used in the rejection below was previously applied and the rejection has been updated to address the new claim amendments.
Claims 1, 2, 4-11, 13-15, 47 and 48 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (US 20080077251, published 27 Mar 2008, listed on IDS filed 24 Feb 2025) in view of Van Osch et al. (WO 2019/073079, published 18 Apr 2019, listed on IDS filed 24 Feb 2025) as evidenced by Fox et al. (Orthopaedic Surgery, vol 1, no. 6, pages 340-351) and evidenced by the instant specification.
Chen teaches production of a devitalized and shaped cartilage graft suitable for recellularizing in vitro, in vivo, or in situ ([0007]). Chen teaches that there are mainly three types of cartilage present in a mammal which are articular or hyaline cartilage, fibrocartilage and elastic cartilage and that fibrocartilage is mainly found in locations including menisci and the annulus fibrosis of the intervertebral disc ([0002]). Chen teaches that the cartilage matrix for the method may come from a fibrocartilage source (see claim 281) and Chen teaches an example of devitalizing a fibrocartilage disc isolated from menisci ([0147]). Thus, it is obvious to devitalize cartilage from a fibrocartilage source such as meniscal cartilage or annulus fibrosis of the intervertebral disc.
Chen teaches the process for devitalization includes steps of cleaning the cartilage graft, treating the graft in a pretreatment solution and treating in an extracting solution to produce a devitalized cartilage graft (claim 12). Chen teaches the use of a pretreatment solution comprising enzymes such as elastase for modifying the extracellular matrix of the cartilage matrix (claims 27 and 28). Chen teaches removing cellular debris using an extracting solution to produce a devitalized cartilage graft ([0010]) and that the term devitalized involves the decellularization or making tissue acellular, such that minimal cellular remnants remain ([0065]). Removing the cellular content renders obvious the decellularized transplant material is free of at least 50-99% or greater of starting cellular content as in claim 8. Regarding claims 4-6 and 48, Chen teaches that the devitalized cartilage graft may be derived from cartilage of human or other animal ([0007]) and teaches and example using fibrocartilage discs isolated form menisci of a cadaver donor ([0147]). Regarding claim 13, Chen teaches an example where after devitalization that osteochondral plugs were incubated with a solution comprising FBS ([0164]), rendering obvious incubating the decellularized transplant material in serum. Chen teaches that the devitalized cartilage graft may be immersed in a storage solution and stored in a sealed container at -80°C (claim 206), rendering obvious claim 14. Regarding claim 15, Chen teaches that the devitalized cartilage may be recellularized to render the tissue vital ([0010]), rendering obvious reintroducing cells into said decellularized transplant material.
Chen does not teach treatment with pepsin (the elected treatment component) or the reduction of elastin or the treatment with freeze/thaw cycles as in claim 10 and does not explicitly teach the removal of blood vessels (claim 7) or the amount of glycosaminoglycan and collagen in the decellularized transplant material as in claim 9. These deficiencies are made up for in the teachings of Van Osch.
Van Osch teaches a method for reducing elastin of a cartilage scaffold containing channels and/or lacunae that allows for recellularization of the scaffold ([0001]). Van Osch teaches that recellularization of the cartilage scaffold is essential to assure fully functional cartilage, maintain the matrix and prevent degradation of the scaffold after transplantation ([0008]) and that the method comprises a step of recellularizing the elastin-reduced cartilage scaffold by allowing cells to adhere into the elastin-reduced cartilage scaffold ([0017]). Van Osch teaches that removing elastin fibers enables cells to invade and attach to the cartilage scaffold ([0009], [0017]). Van Osch teaches that the reduction in elastin is obtained by incubating the cartilage scaffold with one or more enzymes such as elastase ([0011]) and also teaches incubation with at least one other proteolytic enzyme such as pepsin ([0012]). The amount of elastase used in the treatment may be reduced when used in combination with a proteolytic enzyme such as pepsin ([0058]). Regarding claim 11, Van Osch does not teach the specific order of treatment where pepsin is “followed by treatment with elastase,” however, the examiner notes that the selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results, In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946); In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930) (Selection of any order of mixing ingredients is prima facie obvious). Regarding claim 1, Van Osch teaches that the elastin fibers are reduced form the cartilage scaffold to about 50%, 25%, 10%, 1% or complete removal of the elastin fibers prior to the step of reducing elastin fibers form the cartilage scaffold ([0011]).
Van Osch teaches that the cartilage scaffold may be obtained form a human or a xenogenic source ([0010]) and teaches that the sample may be from an animal such as a cow or human and that the human sample may be from post mortem donors or as a surgical specimen resulting from a relevant procedure such as during reshaping of the ear ([0053]) further rendering obvious the human or non-human origin of claims 4 and 48 and the cadaver and living donor sources as in claims 5 and 6. Van Osch teaches that the cartilage sample may be decellularized where chondrocytes in the cartilage samples are killed and dislodged by freeze-thaw cycles to kill cells and help in removing cellular particles ([0054]), rendering obvious the freeze/thaw cycles of claim 10. Van Osch teaches that decellularization refers to removing cells and cell remnants from a cartilage extracellular matrix, leaving a cartilage scaffold of the original tissue ([0028]) and that the cartilage scaffold refers to the extracellular substance of cartilage composed predominantly of collagen fibers, non-collagenous glycoproteins and proteoglycans ([0030]).
Therefore, it would have been prima facie obvious to one of ordinary skill in the
art, before the effective filing date of the claimed invention to have treated a fibrocartilage source such as meniscal cartilage or annulus fibrosis of the intervertebral disc with pepsin and elastase to remove elastin and to treat with freeze/thaw cycles as part of forming a decellularized transplant material. Devitalizing (decellularizing) cartilage material such as meniscal cartilage or annulus fibrosis of the intervertebral disc and recellularizing the material to render it vital is obvious from the teachings of Chen. It is clear from the teaching of Van Osch that the recellularization of decellularized cartilage material is improved by removing elastin as it allows for cells to adhere to the cartilage scaffold. Applying pepsin and elastase is able to remove elastin, as taught by Van Osch, rendering it obvious to use this treatment with the cartilage of Chen to remove elastin and improve the recellularization process. It is further obvious to treat the cartilage material with freeze dry cycles as this is known to aid in killing and dislodging chondrocytes, as taught by Van Osch, thus providing a reasonable expectation of success in improved decellularization form applying freeze dry cycles. Regarding claim 7, as evidenced by the instant specification, menisci treated with pepsin and elastase had blood vessels and elastin fully removed ([0098]). As the same method of treating with pepsin and elastase is known from the art, the result of achieving at least 50% removal of blood vessel content would be a function of the decellularization process rendered obvious. Regarding claim 9, it is obvious to decellularize the cartilage as taught by Chen and that decellularized cartilage refers to the extracellular matrix which is composed of collagen fibers, non-collagenous glycoproteins and proteoglycans, as taught by Van Osch. As evidenced by Fox, collagens comprise up to 75% of the dry weight of the extracellular matrix (page 342 right column) and also contains glycosaminoglycans (page 343 right column). Thus, decellularizing the cartilage material, as rendered obvious from Chen and Van Osch, would necessarily result in a decellularized material with collagen and glycosaminoglycan up to 75% in dry weight, meeting the limitation of claim 9.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references.
Response to Arguments
Applicant's arguments filed 21 Aug 2025 have been fully considered but they are not persuasive. Applicant argues that the removal of at least 70% elastin is much better than what the art can achieve (page 8 of remarks). The applicant argues that the experimental data of Van Osch does not support the teaching of Van Osch of removing elastin fibers (page 8 of remarks). The applicant looks to teaching from Nurnberger et al. (Acta Biomaterialia, 86 (2019)) for evidence that the that the treatment of elastic cartilage with the method of Van Osch of applying pepsin and elastase will not remove at least 70% of elastin (page 9 of remarks). The applicant summarizes by stating that the art does not suggest the use of FMC or IAFC and does not reasonably predict the improved results compared to the use of elastic cartilage (page 9 of remarks).
The examiner is not persuaded by these arguments. The applicant’s arguments focus largely on the teachings of Van Osch and that it would not be possible to remove the large amount of elastin from elastic cartilage by using the method of Van Osch, as is evidenced from alternative teachings of Nurnberger et al. which supposedly demonstrates an incomplete removal of elastin from elastic cartilage. This isn’t persuasive as the rejection is not built on removal of elastin from elastic cartilage but rather the obviousness from the teachings of Chen to devitalize menisci and annulus fibrosis fibrocartilage cartilage grafts, rendering obvious FMC and IAFC, as described in the above rejection. It is known to decellularize fibrocartilage from Chen and the specific removal of elastin is desirable from Van Osch as it allows cells to adhere in the resulting scaffold. Thus, it is obvious to decellularize fibrocartilage materials and to specifically remove elastin as this allows for cells to more easily grow in the resulting scaffold. The specific teaching of Van Osch of achieving certain levels of elastin removal including complete removal further indicates the obviousness of this limitation in the claim as this is a known and desirable outcome. Whether or not the examples of Van Osch were able to achieve the level of elastin removal required in the claim does not take away from the teaching that it is desirable to completely remove the elastin and does not address the removal of elastin that would be achievable from using the fibrocartilage samples rendered obvious by Chen. Thus, the arguments by the applicant are not persuasive.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EDWIN C MITCHELL whose telephone number is (571)272-7007. The examiner can normally be reached Mon-Fri 8:00-5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, David Blanchard can be reached on (571)272-0827. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/E.C.M./Examiner, Art Unit 1619
/ANNA R FALKOWITZ/Primary Examiner, Art Unit 1600