DETAILED ACTION
This action is in reply to papers filed 7/16/2024. Claims 1-18 are pending and examined herein.
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 .
Examiner’s Note
All paragraph numbers throughout this office action, unless otherwise noted, are from the US PGPub of this application US20250090723A1, Published 3/20/2025.
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, 11, 14 and 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 1 recites, inter alia, “compared to normal tissue”. The metes and bounds of this recitation are unclear because it is wholly unclear what the term ‘normal’, in the context of the claim, mean.
Claim 11 recites, inter alia ”… the enzyme aggregates are cross-linked with and without magnetic particles to facilitate controlled removal of contaminants..” The metes and bounds of this claim are unclear because it is unclear whether the aggregates are required to be cross-linked with magnetic particles or not. Note the use of the term “and” in the claim.
Claim 14 recites, inter alia, “…forming tissue modification including channels, grooves or perforations.” The metes and bounds of this claim are unclear. At the outset, claim 14 fails to recite when the tissue modifications are being formed. Does the graft form these modifications prior to removal of contaminants? Does the removal of the contaminants form these modifications? Moreover, how are these modifications formed? Claim 15 is included in this rejection as the limitation recited therein further fuels the lack of clarity regarding claim 14.
Clarification is requested.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Prior Art Rejection 1
Claim(s) 1-5 and 8 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Mills et al. (U.S. Patent 6613278, Published 9/2/2003).
Regarding claim 1, Mills et al. disclose a method for cleaning, perfusing or passivating bony (as in claim 2) implant materials (Col. 5, lines16-18), comprising demineralized tissue (as in claim 5) (Col. 8, line 31+) without at the same time compromising the desirable biological properties of the starting implant materials (Col. 5, lines 54-57) , wherein the implant comprises channels (as in claim 4) (Col. 10, 11-55). Mills discloses as is known in the art, there is substantial variation in the bone inducing properties of different preparations of demineralized bone matrix (DBM) from the same donor, and even wider differences when the DBM, whether in powdered or other form, is derived from different donors (Col. 8, lines 31-59). Mills discloses a wide variety of different cleaning solutions and combinations thereof may be employed according to the method of this invention. For example, the cleaning solutions may include enzymes such as proteases (trypsin, pepsin, subtilisin), lipases, sachrases, and mixtures thereof (as in claim 8) (Col. 19, lines 15-36).
Mills discloses the process of perfusion passivation at Fig. 1A. Specifically, Mills discloses this schematic shows an implant 100 comprising solid structural constituents 110, channels 120, and adventitious materials 130 embedded within the channels 120. The adventitious materials 130 may be cellular debris, bone marrow, cells, lipids (as in claim 1), carbohydrates, proteins, viruses, bacteria, rickettsia, amoebae, fungi and the like. In figure 1A, panels (1) and (2) relate to the first step described above. In panel (1), the channels 120 are primed for back-filling with cleaning solutions by exposing the tissue to decreased pressures. In panel (2), the cleared channels 120 are shown to be substantially clear of adventitious materials 130. Panel (3) relates to steps 2 and 3, wherein molecules of cleaning solution 140 are introduced into a sealed chamber and are driven into the channels 120 by elevated pressures. Panel (4) relates to the fourth step described above, wherein decreased pressure removes remaining cellular debris, cleaning solution 140, and other remaining adventitious materials from the channels 120, and again primes the matrix for deep penetration, now possible due to the clarity of the channels 120. Note that the adventitious materials are significantly reduced (> 70%) in panel 4 (as further in claim 1, claim 3) (Col. 10, lines 12-42). In panels (5)-(7), a one cycle repeat according to the fourth step described above is shown, whereby upon repressurizing with clean solvents, full interpenetration of the solvents into the implant matrix is achieved. In panel (6), reduced pressure draws the remaining solution from the implant, which may then be dried, as shown in panel (7), prior to further processing (e.g. machining according to step 5 above, further cleaning, according to step 6 above), and final packaging of the cleaned tissue. The cycle depicted in FIG. 1A may be repeated as many times as desired to ensure complete internal cleaning of the matrix interior. In FIG. 1B, a representation of the pressure and fluid oscillation throughout the various steps of the above described process is represented. (Col. 10, lines 42-55)
Accordingly, Mills anticipates the claimed invention.
Prior Art Rejection 2
Claim(s) 9, 13-15 and 18 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Mills et al. (U.S. Patent 6613278, Published 9/2/2003).
Regarding claim 9, Mills et al. disclose a method for cleaning, perfusing or passivating bony implant materials, comprising demineralized tissue, without at the same time compromising the desirable biological properties of the starting implant materials, wherein the implant comprises channels (Col. 10, 11-55). Mills disclose as is known in the art, there is substantial variation in the bone inducing properties of different preparations of demineralized bone matrix (DBM) from the same donor, and even wider differences when the DBM, whether in powdered or other form, is derived from different donors. Mills discloses a wide variety of different cleaning solutions and combinations thereof may be employed according to the method of this invention. For example, the cleaning solutions may include enzymes such as proteases (trypsin, pepsin, subtilisin), lipases, sachrases, and mixtures thereof (as in claim 13) (Col. 19, lines 15-36).
Mills discloses the process of perfusion passivation at Fig. 1A. Specifically, Mills discloses this schematic shows an implant 100 comprising solid structural constituents 110, channels 120 (as in claim 14), and adventitious materials 130 embedded within the channels 120. Mills discloses the graft is cut (as in claim 15) (Col. 24, lines 1-10). The adventitious materials 130 may be cellular debris, bone marrow, cells, lipids (claim 9), carbohydrates, proteins, viruses, bacteria, rickettsia, amoebae, fungi and the like. In figure 1A, panels (1) and (2) relate to the first step described above. In panel (1), the channels 120 are primed for back-filling with cleaning solutions by exposing the tissue to decreased pressures. In panel (2), the cleared channels 120 are shown to be substantially clear of adventitious materials 130. Panel (3) relates to steps 2 and 3, wherein molecules of cleaning solution 140 are introduced into a sealed chamber and are driven into the channels 120 by elevated pressures. Panel (4) relates to the fourth step described above, wherein decreased pressure removes remaining cellular debris, cleaning solution 140, and other remaining adventitious materials from the channels 120, and again primes the matrix for deep penetration, now possible due to the clarity of the channels 120. Note that the adventitious materials are significantly reduced (> 70%) in panel 4 (as further in claim 9) (Col. 10, lines 12-42).In panels (5)-(7), a one cycle repeat according to the fourth step described above is shown, whereby upon repressurizing with clean solvents, full interpenetration of the solvents into the implant matrix is achieved. In panel (6), reduced pressure draws the remaining solution from the implant, which may then be dried, as shown in panel (7), prior to further processing (e.g. machining according to step 5 above, further cleaning, according to step 6 above), and final packaging of the cleaned tissue. The cycle depicted in FIG. 1A may be repeated as many times as desired to ensure complete internal cleaning of the matrix interior. In FIG. 1B, a representation of the pressure and fluid oscillation throughout the various steps of the above described process is represented (Col. 10, lines 42-55). Mills discloses employing a vacuum extraction (as in claim 18) (Col. 11, lines 31+).
Accordingly, Mills anticipates the claimed invention.
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.
Prior Art Rejection 3
Claim(s) 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Mills et al. (U.S. Patent 6613278, Published 9/2/2003) as applied to claims 1-5 and 8 and further in view of Zhang et al. (Cell Tissue Bank. 2014 Sep;15(3):357-67.)
The teachings of Mills et al. are relied upon as detailed above. And although Mills teaches using lipase, Mills fails to teach using lipase with activity from 0-40 °C (as in claim 6) and wherein a minimum dose of .01% lipid substrate in the graft is used to treat the graft (as in claim 7).
Before the effective filing date of the claimed invention, Zhang et al. sought to evaluate the efficacy of lipase to defat lipids in the bone (Pg. 359, Col. 1). To this end, Zhang soaked porcine cancellous bone in 1 % lipase (as in claim 7) for 4 h in a shaker at 40 °C (as in claim 6) (Pg. 359, Col. 1, para. 1). Zhang teaches the lipids content in bone grafts processed by lipase achieved a very low level of 0.46 ± 0.16 % (Fig. 1). Observed by SEM (Fig. 2), there were no lipid droplets on surface of the bone grafts (Pg. 361, Col. 1, par. 3).
When taken with the teachings of Mills et al., wherein Mills teaches cleaning contaminated bone using an enzyme, one of ordinary skill in the art would have found it prima facie obvious to use lipase at the concentration and temperature set for the in Zhang et al. because Zhang observed success in removing lipids from the surface of the bone grafts.
Thus, the modification would have been prima facie obvious.
Prior Art Rejection 4
Claim(s) 10-12 are rejected under 35 U.S.C. 103 as being unpatentable over Mills et al. (U.S. Patent 6613278, Published 9/2/2003) as applied to claims 9, 13-14 and 18 and further in view of Jenewein et al. (PgPub US20190292494A1, Published 9/26/2019), Van Pelt et al. (WO2018004341A1, Published 1/4/2018) and Chen et al. (PgPub US20090024223A1, Published 1/22/2009).
The teachings of Mills et al. are relied upon as detailed above. And although Mills teaches the cleaning solutions includes enzymes such as proteases (trypsin, pepsin, subtilisin), lipases, sachrases, and mixtures thereof (as in claim 13), Mills fails to teach enzyme aggregates (as in claim 10).
Before the effective filing date of the claimed invention, Jenewein taught that enzymes tend to be destabilized if they remain in a liquid environment, especially if they remain in an aqueous environment. Therefore, Jenewein teaches liquid enzyme products may be stabilized by methods such as addition of chemicals, or liquid enzyme products may be converted to an anhydrous form by lyophilization or spray-drying e.g. in the presence of a carrier material to form aggregates (as in claim 10) (Pg. 1, para. 2).
Van Pelt teaches cross-linked enzyme aggregate (CLEA) comprising magnetizable particles (as in claim 11) (Abstract). Van Pelt teaches CLEA particles, contain two or more different enzymes in the aggregate () (Pg. 5, lines 11-15) have a diameter size in the range of 1- 50 µm (as in claim 12 ) (Pg. 4, lines 5-19). Van Pelt notes that in enzymatic processes that are performed at an industrial scale, it is important that the enzyme has a long-term operational stability and that recovery and re-use of the enzyme are efficient and convenient. Van Pelt teaches these requirements can be met by using enzymes in an immobilized form (Pg. 1, para. 2).
However, none of Mills et al., Jenewein et al., and Van Pelt et al. teach the tissue graft is a biphasic osteochondral tissue graft (as in claim 12).
Before the effective filing date of the claimed invention, Chen et al. teach osteochondral plugs made by cutting the cylindrical bone portion (7) to obtain one or more gaps (9) that form angles between about 0 to about 180 degrees along the entire length of the bone portion up to the cartilage and osteochondral bone interface (as further in claim 12) (Pg. 4, para. 69).
When taken with the teachings of Mills et al., wherein Mills teaches cleaning contaminated bone using an enzyme, one of ordinary skill in the art would have found it prima facie obvious to use cross-liked enzyme aggregates, as set forth in Van Pelt, to clean the surface of the contaminated bone of Mills. The skilled artisan would have found it prima facie obvious to do so because Jenewein taught that enzymes tend to be destabilized if they remain in a liquid environment and that the aggregation of enzymes provides stability. Moreover, one of ordinary skill in the art would have found it prima facie obvious to use the aggregated enzymes to clean the osteochondral plugs of Chen prior to implantation in order to determine the aggregated enzymes’ efficacy in cleaning a biphasic graft.
Thus, the modification would have been prima facie obvious.
Prior Art Rejection 5
Claim(s) 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Mills et al. (U.S. Patent 6613278, Published 9/2/2003) as applied to claims 9, 13-14 and 18 and further in view of Blaudszan et al. (DE3720992A1, Published 2/1/1990).
The teachings of Mills et al. is relied upon as detailed above. However, Mills et al. fails to teach the method comprising cryoablation with liquid gas or biocompatible cryogens (as in claim 16).
Before the effective filing date of the claimed invention, Blaudszan et al. teach abrasive blasting of contaminated surfaces, in which CO2 (as in claim 17) dry ice particles are directed against the surface with the help of a propellant jet (Abstract). Specifically, Blaudszan teaches forming CO2 by forming droplets in cryogenic cooling medium into CO2 particles, for example by spraying the liquid CO2 into a deep-freeze gas atmosphere (as in claim 16)Pg. 12,para. 25).
When taken with the teachings of Mills et al., wherein Mills teaches cleaning contaminated bone using an enzyme, one of ordinary skill in the art would have found it prima facie obvious to use the method of Blaudszan et al. wherein Blaudszan cleans contaminated surfaces by blasting CO2 directed against a surface. The skilled artisan would have found it prima facie obvious to do so in order to determine the efficacy of Blaudszan’s method in treating contaminated bony surfaces.
Thus, the modification would have been prima facie obvious.
Authorization to Initiate Electronic Communications
The examiner may not initiate communications via electronic mail unless and until applicants authorize such communications in writing within the official record of the patent application. See M.P.E.P. § 502.03, part II. If not already provided, Applicants may wish to consider supplying such written authorization in response to this Office action, as negotiations toward allowability are more easily conducted via e-mail than by facsimile transmission (the PTO's default electronic-communication method). A sample authorization is available at § 502.03, part II.
Conclusion
No claim is allowed.
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/TITILAYO MOLOYE/ Primary Examiner, Art Unit 1632
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