DETAILED ACTION
Status of the Claims
Claims 2, 5-20 are pending in the instant application. Claims 13-20 have been withdrawn based upon Restriction/Election as discussed below. Claims 2 and 5-12 are being examined on the merits in the instant application.
Advisory Notice
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
All rejections and/or objections not explicitly maintained in the instant office action have been withdrawn per Applicants’ claim amendments and/or persuasive arguments.
Priority
The instant Application is the U.S. entry (371) of PCT/US2021/013464 filed 01/14/2021. And claims priority to U.S. Provisional Application 62/961,138 filed 01/14/2020.
The U.S. effective filing date for claims 2 and 5-8 has been determined to be 01/14/2020, the filing date of 62/961,138. The U.S. effective filing date for claims 9-12 has been determined to be 01/14/2021, the filing date of PCT/US2021/013464. The examiner finds no support for a third component, as recited in claims 9-12, in 62/961,138.
Response to Arguments:
Applicant's arguments filed 09/19/2025 have been fully considered but they are not persuasive.
Applicant argues that: “The Field of the Invention, paragraph [0001], as well as paragraph [0007] of the Detailed Description, of the '138 Provisional describes a generic embodiment of the presently claimed multiple component tissue-derived graft as comprising "two or more components, each of which is a tissue-derived matrix and at least two of which are derived from different types of tissue" (emphasis added). In fact, paragraph [0019] further clearly discloses that "[i]n some embodiments, the multiple component graft comprises more than two components" (emphasis added), which necessarily means possibly 3, or 4, or 5, or even more, components. This plain language, clearly discloses and contemplates embodiments of the multiple component tissue-derived graft which comprise not only two components, but also three, or four, or five, or six, or even more, components, wherein each component is a tissue-derived matrix.” (paragraph bridging pp. 11-12). And that: “In view of the foregoing evidence and explanations, Applicant asserts that Claims 9-12 are also entitled to a priority date of January 14, 2020, based on the' 138 Provisional. Withdrawal of the Examiner's initial priority determination for Claims 9-12 and acknowledgement that Claims 9-12 are entitled to the priority date of January 14, 2020, from the filing date of the '138 Provisional, are hereby respectfully requested.” (p. 13, last paragraph).
In response the examiner argues that the disclosure in the as-filed instant application is different from that of the Provisional Application ‘138, and particularly specifically discloses/describes a third component in addition to the first and second. For example “As mentioned above, according to the invention described and contemplated herein, the multiple component graft comprises at least a first component and a second component which are assembled together, either before or during implanting proximate a tissue defect. The designation of "first," "second," "third," etc., regarding each component of any embodiment of the multiple component tissue graft is not intended to, and does not, indicate or require any particular order of assembly or implantation, but rather is intended only to be useful in distinguishing between the two or more components of any particular multiple component graft. For example, a multiple component graft which comprises first, second, and third components does not have to be assembled with the first, second and third components in sequential order according to those designations. Rather, when such a multiple component graft is assembled prior to implantation, for example without limitation, the third component may be positioned and assembled in between the second and first components, or the first component may be positioned between the second and third components. Similarly, when such a multiple component graft is assembled during implanting proximate a tissue defect, the components may be implanted in any order, i.e., with any of the third, second, or first being implanted first, and any of the first, second, or third components being implanted last.” [emphasis added](p. 7-6, [0020]). And further that: “Another exemplary embodiment of a multiple component graft in accordance with the description provided herein and which could be useful for more effectively treating an osteochondral defect could comprise three components including: a first component comprising a bone-derived matrix, a second component comprising a multiple tissue matrix which includes mixed bone and cartilage matrices, and a third component comprising a cartilage-derived matrix.” [emphasis added](p. 14, [0038]). And further that: “In some embodiments, the multiple component graft comprises three or more components. For example, without limitation, the multiple component graft may comprise a first component comprising a bone-derived matrix, and a second component comprising a cartilage-derived matrix, and a third component comprising a placenta-derived matrix. In such embodiments, any one or more of the first, second and third components may be a tissue-derived matrix or a multiple tissue matrix. For example, without limitation, the first component may comprise two or more types of bone-derived matrices, such as a cortical bone-derived matrix and a cancellous bone-derived matrix, as described above in other exemplary embodiments. In some embodiments, the third component may comprise two or more types of placenta-derived matrices, such as two or more of an amnion-derived matrix, a chorion-derived matrix, and an umbilical cord-derived matrix. Additionally, in such embodiments, each of the tissue-derived matrices or multiple tissue matrices comprising the first, second, and third components, has at least one physical form which may be the same or different physical form as the other matrices. Furthermore, any one or more of the first, second and third components may be viable or not. Any one or more of the first, second and third components may include one or more additional materials.” [emphasis added](p. 19, [0049]).
It is very clear from reading the instant Specification that ample guidance to “a multiple component graft which comprises first, second, and third components” for example a “multiple component graft may comprise a first component comprising a bone-derived matrix, and a second component comprising a cartilage-derived matrix, and a third component comprising a placenta-derived matrix.” There is no such disclosure/description in the Provisional Application ‘138, therefore for claims that specifically require “a third tissue-derived matrix” (instant claims 9-12), the priority date is properly 01/14/2021, the filing date of PCT/US2021/013464.
Claim Rejections
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 2 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Instant claim 2 has been amended to depend from instant claim 5 which places instant claim 2 in improper dependent form. MPEP 608.01(n)(III) requires a claim in proper dependent form to “reference a claim previously set forth”. When examining a dependent claim, the examiner should determine whether the claim complies with 35 U.S.C. 112(d), which requires that dependent claims contain a reference to a previous claim in the same application, specify a further limitation of the subject matter claimed, and include all the limitations of the previous claim. If the dependent claim does not comply with the requirements of 35 U.S.C. 112(d), the examiner should reject the dependent claim under 35 U.S.C. 112(d) as unpatentable rather than objecting to the claim. See Pfizer, Inc. v. Ranbaxy Labs., Ltd., 457 F.3d 1284, 1291-92, 79 USPQ2d 1583, 1589-90 (Fed. Cir. 2006).
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 2 and 5-8 remain rejected under 35 U.S.C. 103 as being unpatentable over MCKAY (US 2006/0247790; published November, 2006) in view of RICHARDSON (WO 2019/068660 A11; published April, 2019) and NASERT (US 2017/0049930; published February, 2017).
Applicants Claims
Applicant claims a multiple component graft for treating a tissue defect, comprising two or more components, each of which comprises a tissue-derived matrix or a multiple tissue matrix, wherein at least two of the components are derived from and comprise different types of tissue, wherein the two or more components comprise at least: a first component which comprises a first tissue-derived matrix or a first multiple tissue matrix which includes at least a first type of tissue and at least one physical form, and a second component which comprises a second tissue-derived matrix or a second multiple tissue matrix which includes at least a second type of tissue which is different from the first type of tissue and at least one physical form, wherein the at least one physical form of the first component and of the second component are selected from pieces, granules, particles, powder, fibers, putty, and a combination thereof, and may be the same or different from one another (instant claim 5).
Elected Species: Applicants have elected the following species in the reply filed 04/22/2025: (a) a species of two or more components, each with specificity to (i) a tissue matrix and (ii) a tissue type is a first component (i) granules and (ii) bone; and a second component (i) fibers and (ii) cartilage. And (b) one or more additional materials, with specificity to each material is (i) extracellular matrix biomaterials.
Determination of the scope
and content of the prior art (MPEP 2141.01)
MCKAY teaches shaped osteochondral grafts and methods of using the same (title), and particularly "Described are plug grafts and in particular embodiments osteochondral plug grafts and grafting methods which utilize unique plug geometries and cooperative graft/host tissue interfaces to improve stability of grafted plugs within host tissue. Embodiments of the invention include harvested osteochondral or synthetic plug grafts having bore geometries other than circular cylinders and which are implantable in correspondingly prepared host sites to resist rotation and improve stability." (Abstract, see whole document). MCKAY teaches that: "Osteochondral grafts of the invention can be used in the repair of articular cartilage in patients, including for example that occurring in weight bearing joints such as those noted above and especially in the knee. The articular cartilage in need of repair can, for example, present a full thickness defect, including damage to both the cartilage and the underlying subchondral bone. Such defects can occur due to trauma or due to advanced stages of diseases, including arthritic diseases." ([0038]).
MCKAY teaches that: "With reference now to FIGS. 4 and 5, shown are top and perspective views, respectively, of another multi-lobed osteochondral graft of the present invention. Graft 50 also includes a cartilage layer 52 attached to an underlying bone body 54." [emphasis added]([0041 ]). The Graft 50 includes a first tissue matrix which is a cartilage layer (52), and a second tissue matrix which is bone tissue (54) which are regarded as different tissue types (instant claim 2, line 2).
MCKAY teaches that: “The inventive osteochondral graft includes an osteochondral plug graft having a cartilage cap and a body of bone attached to the cartilage cap. The body of bone includes a stabilizing portion for receipt within the surgical opening, wherein the stabilizing portion of the bone body presents an external three-dimensional contour other than a circular cylinder. The stabilizing portion is further configured for mated receipt within the surgical opening to provide a mechanical interlock against rotation. In certain embodiments, osteochondral graft plugs include a body of bone having a cross-sectional profile that is non-circular but includes at least a portion defining an arc of a circle. Illustratively, such osteochondral graft plugs can take the form of multi-lobed grafts, wherein each lobe has a cross-sectional profile forming an arc of a circle. Such grafts may have two, three, four, or more such lobes. In further embodiments, osteochondral graft plugs of the invention can have bone bodies with polygonal cross-sectional profiles such as triangular, rectangular (including square), heptagonal, hexagonal, etc. cross-sectional profiles. Such grafts, or synthetic grafts having similar features, can for example be implanted into surgically prepared openings of similar shape to provide implanted grafts locked against rotation. As well, embodiments of the invention provide grafts including a bone body having an ovate cross-sectional profile, which can be implanted in openings of similar shape.” ([0009])(instant claim 3-4, three-dimensional shape).
MCKAY teaches that: “In this regard, such grafts may have a uniform composition throughout, or may vary, for instance having a plug body formed of a first, relatively strong and loadbearing material (e.g. a ceramic, polymer or composite), and a cap formed of another material to provide the articulating surface formed by another material, for example a relatively smooth polymer layer. These and other variants will be apparent to the skilled artisan from the descriptions herein.” ([0051])(instant claims 5-6).
MCKAY teaches that: “Growth factor may be applied to the tissue source in the form of a buffered aqueous solution. Other materials which may be suitable for use in application of the growth factors in the methods and products of the present invention include carrier materials such as collagen, milled cartilage, hyaluronic acid, […]” ([0055]). And that: “Other biologically active materials may also be used in conjunction with osteochondral grafts of the present invention. These include for example cells such as human allogenic or autologous chondrocytes, human allogenic cells, human allogenic or autologous bone marrow cells, human allogenic or autologous stem cells, […].” ([0056])(instant claim 7).
MCKAY teaches that: “When used, the growth factor and/or other material(s) can be applied directly to the plug graft and/or to the site in need of repair. For example, the growth factor and/or other material may be physically applied to the graft ( e.g. the bone and/or cartilage tissue of an osteochondral graft) through spraying or dipping, or using a brush or other suitable applicator, such as a syringe. Alternatively, or in addition, amounts of the growth factor or other material(s) can be directly applied to the site in need of tissue repair, for example by filling or coating the surgically-prepared opening with one or more of these substances.” ([0058])(instant claim 8).
Ascertainment of the difference between
the prior art and the claims (MPEP 2141.02)
The difference between the rejected claims and the teachings of MCKAY is that MCKAY does not expressly teach the physical form of the bone is granules or that the physical form of the cartilage is fibers (instant claim 6, elected species).
RICHARDSON teaches “A kit of parts for assembly into a joint plug, the joint plug for insertion within an opening of a bone layer in a joint and through a cartilage layer on the bone layer, the kit of parts comprising: a bone scaffold portion for accommodating bone tissue therein, said bone scaffold portion being configured for insertion into the opening of the bone layer; a cartilage scaffold portion for accommodating cartilage tissue, said cartilage scaffold portion being configured to be positioned over the bone scaffold portion; a permeable membrane portion configured to be provided over the cartilage scaffold portion; and further comprising bone scaffold engagement means for mounting the cartilage scaffold portion on the bone scaffold portion.” (abstract, see whole document).
RICHARDSON teaches that: “the bone scaffold portion may be in the form of granules” (p. 8, [0043])(instant claim 6, physical form of bone is granules).
NASERT teaches cartilage-derived implants (title), the: “Cartilage fibers and implants made therefrom are disclosed, with and without cartilage particles. Methods for making the cartilage fibers and the implants containing them are also disclosed. The implants may be pre-shaped and may be reshapable and provide good shape retention and little swelling when placed into a cartilage defect.” (abstract, see whole document).
Finding of prima facie obviousness
Rationale and Motivation (MPEP 2142-2143)
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 produce a multiple component shaped osteochondral grafts including a cartilage portion and a bone, as suggested by MCKAY, the bone tissue being in the form of granules, as suggested by RICHADSON, and the cartilage being in the form of fibers, as suggested by NASERT, as granules and fibers are taught as suitable physical forms for bone and cartilage grafts/implants (MPEP §2144.07).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention because it would have required no more than an ordinary skill in the art to produce a osteochondral graft as taught by MCKAY. Therefore, the invention as a whole would have been 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, especially in the absence of evidence to the contrary.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a).
Claims 9-12 remain rejected under 35 U.S.C. 103 as being unpatentable over MCKAY in view of RICHARDSON and NASERT as applied to claims 1-8 above, and further in view of KOOB (US 2016/0199537; published July, 2016).
Applicants Claims
Applicant claims a multiple component graft for treating a tissue defect, comprising two or more components, each of which comprises a tissue-derived matrix or a multiple tissue matrix, wherein at least two of the components are derived and comprise different types of tissue (instant claim 1). Applicant further claims the multiple component graft comprises a third component which comprises a third tissue-derived matrix or a third multiple tissue matrix which includes at least a third type of tissue, which is different from the first and second types of tissue, and at least one physical form (instant claim 9). Applicant further claims the third component comprises an amnion-derived matrix and the third type of tissue is amnion, and the at least one physical form of each of the bone-derived matrix, cartilage-derived matrix and amnion-derived matrix is, independently selected from pieces, granules, particles fibers, putty and a combination thereof (instant claim 10).
Determination of the scope
and content of the prior art (MPEP 2141.01)
MCKAY teaches shaped osteochondral grafts and methods of using the same, as discussed above and incorporated herein by reference.
MCKAY teaches that: “Growth factor may be applied to the tissue source in the form of a buffered aqueous solution. Other materials which may be suitable for use in application of the growth factors in the methods and products of the present invention include carrier materials such as collagen, milled cartilage, hyaluronic acid, […]” ([0055]). And that: “Other biologically active materials may also be used in conjunction with osteochondral grafts of the present invention. These include for example cells such as human allogenic or autologous chondrocytes, human allogenic cells, human allogenic or autologous bone marrow cells, human allogenic or autologous stem cells, […].” ([0056])(instant claim 11).
MCKAY teaches that: “When used, the growth factor and/or other material(s) can be applied directly to the plug graft and/or to the site in need of repair. For example, the growth factor and/or other material may be physically applied to the graft ( e.g. the bone and/or cartilage tissue of an osteochondral graft) through spraying or dipping, or using a brush or other suitable applicator, such as a syringe. Alternatively, or in addition, amounts of the growth factor or other material(s) can be directly applied to the site in need of tissue repair, for example by filling or coating the surgically-prepared opening with one or more of these substances.” ([0058])(instant claim 12).
RICHARDSON teaches bone/cartilage scaffold, as discussed above and incorporated herein by reference.
NASERT teaches cartilage-derived implants, as discussed above and incorporated herein by reference.
Ascertainment of the difference between
the prior art and the claims (MPEP 2141.02)
The difference between the rejected claims and the teachings of MCKAY et al. is that MCKAY et al. do not expressly teach the third component, amnion-derived matrix (instant claims 9-12).
KOOB teaches collagen reinforced tissue grafts (title), and particularly that: “This invention is directed to a multi-layered tissue graft comprising a collagen layer and at least one separated and washed placental tissue component and/or umbilical cord component, wherein the collagen is human collagen substantially free of non-human antigens.” (abstract, see whole document).
KOOB teaches that: “The term ‘amnion’ as used herein includes amniotic membrane where the intermediate tissue layer is intact or has been substantially removed.” And further: “The term ‘placental tissue’ refers to any and all of the well-known components of the placenta including but not limited to amnion, chorion, and the like, and including processed tissue, such as dehydrated placental tissue and micronized placental tissue. The term ‘placental tissue’ as used herein does not include any of the umbilical cord components(e.g., Wharton's jelly, umbilical cord vein and artery, and surrounding membrane).” ([0018]). And that: “‘Collagen,’ as used herein, refers to biocompatible collagen derived from immune-privileged human tissue, such as placental tissue or an umbilical cord. The collagen, once obtained from human immune-privileged human tissue, may be in any form, such as a gel, gelatin, fibril, slurry, hydrogel or a film. It should be noted that the fibrous layer of amnion (i.e., the basement membrane) contains collagen types IV, V, and VII.” ([0019]).
KOOB teaches that: “In some embodiments, the multi-layered tissue graft includes from 1 to 10 wt%, 10 to 20 wt%, 20 to 30 wt%, 30 to 40 wt %, 40 to 50 wt %, 50 to 60 wt %, 60 to 70 wt %, 70 to 80 wt% amnion relative to the total weight of the multilayered tissue graft.” ([0048]).
KOOB teaches that: “In some embodiments, the fibroblast layer of the amnion
layer(s) acts as an adhesive for the next layer.” ([0059]). And that: “The designation "amnion/collagen/amnion," for example, means that a layer of collagen is interposed between two layers of amnion. It is important to note that when multiple amnion layers are used, it is not necessary to partially remove the epithelial cells from the basement membrane for those layers that are not in direct contact with host cells.” ([0061]).
KOOB teaches that: “In one aspect, the grafts or micronized pharmaceutical compositions described herein are useful in enhancing or improving wound healing.” ([0095]).
KOOB teaches that: “In another aspect, the tissue grafts or micronized pharmaceutical compositions can be used in the treatment of bone defects and bone repair.” ([0113]). And that: “Amnion contains growth factors such as EGF, bFGF, and PDGF that promote wound healing and re-epithelialization. Not wishing to be bound by theory, the application of a topical composition composed of the tissue grafts or micronized compositions described herein where the epithelial layer of the skin is disrupted can be effective in delivering the growth factors directly to the injured site to promote healing. Amnion is a unique ECM due to the presence of collagen types IV, V and VII, which enables the amnion to bind water and swell.” ([0119]).
Finding of prima facie obviousness
Rationale and Motivation (MPEP 2142-2143)
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 produce a multiple component shaped osteochondral grafts including a cartilage portion and a bone, as discussed above, and further to include an amnion layer as an adhesive between layers, for example, between bone/cartilage layers in MCKAY, and/or no promote wound healing re-epithelialization due to the growth factors in the amnion, as suggested by KOOB.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention because it would have required no more than an ordinary level of skill to incorporated amnion in the bone/cartilage osteochondral grafts taught by MCKAY. Therefore, the invention as a whole would have been 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, especially in the absence of evidence to the contrary.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
Response to Arguments:
Applicant's arguments filed 09/19/2025 have been fully considered but they are not persuasive.
Applicant argues that (1) “the combination of McKay and Richardson is not proper in view of the actual teachings of Richardson which are not at all related to tissue-derived matrices or graft components made therefrom.” (2) “McKay teaches away from combination with teachings for modification of the bone body of the osteochondral plug graft disclosed in McKay to a particulate form or other small pieces […] even if Richardson were reasonably applicable to tissue-derived matrices and graft components comprising them.” (3) “No Modification That Weakens Mechanical Strength of Bone Body” particularly that “persons of ordinary skill to avoid treatments that weaken the bone body, such as reduction to smaller pieces or particle form.” and (4) “No Reasonable Expectation of Success For Reducing Bone Body to Pieces/Particles Where Cartilage Layer Naturally Attached Thereto When Harvested.” (pp. 15-25).
In response to (1) MCKAY clearly teaches that: “In certain aspects of the present invention, an osteochondral plug graft for treating an articular cartilage defect includes a bone body with sidewalls having a cross sectional profile other than a circular cylinder. […] Osteochondral plug grafts of the invention having such shapes can be configured for receipt within surgically prepared openings in a human or other mammalian knee” ([0036]). And RICHARDSON teaches that: “In accordance with an aspect of the present invention, there is provided a kit of parts for assembly into a joint plug. The joint plug is for insertion within an opening of a bone layer in a joint and through a cartilage layer on the bone layer.” ([0010]), “In one embodiment, the joint plug of the present invention may be used in ACI (autologous chondrocyte implantation), for example as a knee-plug.” ([0013]). Both MCKAY and RICHARDSON, consistent with the instant Specification Example (p. 23 [00061] through p. 24, [00064]) clearly suggest knee implants for repairing knee joints. Therefore, the combination is clearly proper.
In (1) Applicant particularly argues that: “neither the bone or cartilage scaffold portions, respectively, comprise bone tissue or cartilage tissue harvested from donors, disclosed in McKay (harvested subchondral bone with a cartilage layer attached thereto) and recited for the presently claimed invention (at least first and second components, each of which comprises a tissue-derived matrix or a multiple tissue matrix; see amended independent Claim 5).” (paragraph bridging pp. 15-16). And that: “Furthermore, Richardson describes and contemplates that chondrocytes are added to the bone scaffold portion and chondrocytes are added to the cartilage scaffold portion, and that each portion is provided with openings or pores for "accommodating" the aforesaid cells which tissue growth in and propagating out of the scaffold portions. (Richardson, paragraphs [0014]-[0015]; see also paragraphs [0040] and [0050]). Thus, the terminology used in Richardson for the scaffold portions is indicative of what type of tissue is expected to growth therein and may guide the size of the accommodating openings or pores therein. In other words, as disclosed in Richardson, the bone scaffold portion includes "bone" in its name because it provides a scaffold for the growth of bone tissue, and the cartilage scaffold portion includes "cartilage" in its name because it provides a scaffold for the growth of cartilage tissue.” (p. 16, 2nd paragraph). And further that: “With the benefit of the foregoing understanding of what Richardson actually describes, it is clear that, contrary to the Examiner's reading, the statement in paragraph [0043] that "the bone scaffold portion may be in the form of granules or a powder matrix that supports bone tissue growth" does not actually mean, teach, or suggest, bone tissue-derived granules or powder may be included in the bone scaffold portion of the disclosed joint plug. Paragraphs [0035]-[0039] of Richardson clearly describe the bone scaffold portion of the joint plug as being formed from a biodegradable or non-biodegradable materials, such as ceramic or composite material, including bioactive glasses, natural and synthetic polymers, magnesium alloys, etc. The cartilage scaffold portion of the joint plug is described in paragraphs [0044]-[0046] as being formed from biodegradable or non-biodegradable material such as a hydrogel, polymer or composite material, including several types of polymers, synthetic proteins, polyaminoacids, and polysaccharides, such as one or more of gelatin, elastin, and sodium hyaluronate.” (paragraph bridging pp. 16-17). And “In the foregoing circumstances, Applicant respectfully submits that the proposed combination of McKay and Richardson is inappropriate and would not lead persons of ordinary skill in the relevant art to develop a harvested bone body comprising subchondral bone tissue (McKay) in the form of granules or other particles (Richardson) since the materials disclosed in Richardson for a joint plug are not tissue-derived at all.” (p. 17, 2nd paragraph).
In response the examiner argues that applicants own Specification clearly suggest that tissue-derived matrices (autogenic, allogenic, xenogenic, or combinations thereof) “are produced and available in any of several different physical forms including, without limitation, pieces, particles, fibers, powder, sheets, putty, flowable fluid, three-dimensional shapes which are monolithic, multi-piece, or otherwise formed (e.g., molded or otherwise shaped) from particles, fibers, pieces, as well as combinations of any of the foregoing physical forms. Many such tissue-derived matrices and grafts comprising them have been shown to enable, facilitate, and/or enhance one or more of tissue healing, repair, and regeneration at the tissue defect.” (p. 1, Background of Invention, [0004]). Additionally, MCKAY clearly teaches that: “While certain discussions above have focused upon the use of harvested osteochondral plug grafts, in other aspects of the invention, plug grafts of and for use in the invention can be manufactured from other materials or components. Illustratively, plug grafts adapted for receipt in surgical openings in subchondral bone at articular sites, and desirably for integration with the subchondral bone, can be synthesized from natural or synthetic materials. […] Suitable ceramic materials include, for example, calcium phosphate ceramics such as tricalcium phosphate, hydroxyapatite, and biphasic calcium phosphate. These or other suitable materials can be used to form plug grafts useful in articular cartilage resurfacing procedures. In this regard, such grafts may have a uniform composition throughout, or may vary, for instance having a plug body formed of a first, relatively strong and loadbearing material (e.g. a ceramic, polymer or composite), and a cap formed of another material to provide the articulating surface formed by another material, for example a relatively smooth polymer layer. These and other variants will be apparent to the skilled artisan from the descriptions herein.” ([0051]). Therefore, one of ordinary skill in the art would have clearly recognized that tissue-derived matrices such as bone and/or cartilage as described by MCKAY could have been provided in the form of granules, “the bone scaffold portion my be in the form of granules” as described by RICHARDSON ([0043]), and cartilage fibers as described by NASERT, and consistent with Applicants own description of the prior art.
Additionally, it would have been within the ordinary level of skill in the art to include tissue-derived bone granules as described by MCKAY, “Osteochondral plug grafts of and for use in the invention can be harvested from the recipient or from a suitable human or other animal donor” ([0034]), “Osteochondral grafts of the invention can be harvested at their final shape for implant or can be manipulated after harvest to provide the desired shape.” ([0035]). “In the case of allograft osteochondral plugs, these can be either fresh (containing live cells) or processed and frozen or otherwise preserved to remove cells and other potentially antigenic substances while leaving behind a scaffold for patient tissue ingrowth. A variety of such processing techniques are known and can be used in accordance with the invention. […] These and other conventional tissue preservation techniques can be applied to the osteochondral grafts in accordance with the present invention.” ([0037]). “Suitable ceramic materials include, for example, calcium phosphate ceramics such as tricalcium phosphate, hydroxyapatite, and biphasic calcium phosphate.” ([0051]). “Other biologically active materials may also be used in conjunction with osteochondral grafts of the present invention. These include for example cells such as human allogenic or autologous chondrocytes, human allogenic cells, human allogenic or autologous bone marrow cells, human allogenic or autologous stem cells, demineralized bone matrix, […].” ([0056]).
In response to (2), Applicant argues that “McKay teaches away from combination with teachings for modification of the bone body of the osteochondral plug graft disclosed in McKay to a particulate form or other small pieces […] even if Richardson were reasonably applicable to tissue-derived matrices and graft components comprising them.”, the examiner argues that nothing in MCKAY suggests that bone granules cannot be used in their osteochondral grafts. In the instant case a person having ordinary skill in the art to which the invention pertains would have understood that bone tissue can be utilized in the form of granules as per the broad teachings of MCKAY and RICHARDSON. In deciding KSR International Co. v. Teleflex Inc. (550 US 398; 82 USPQ2d 1358, 1397 (2007)) the court emphasized that "[a] person of ordinary skill in the art, is also a person of ordinary creativity, not an automaton" Additionally, is clear that “The hypothetical ‘person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art,” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988) (MPEP § 2144.03). In the instant case a person having ordinary skill in the art to which the invention pertains would have understood the scientific principles governing the operation of a bone implant materials. Specifically a person having ordinary skill in the art would have recognized that tissue-derived bone material can be utilized in the form of granules.
In response to (3) “No Modification That Weakens Mechanical Strength of Bone Body” particularly that “persons of ordinary skill to avoid treatments that weaken the bone body, such as reduction to smaller pieces or particle form.”, the examiner argues that there is no evidence that use of bone granules would necessarily weaken the bone body. Again both MCKAY and RICHARDSON, consistent with the instant Specification Example (p. 23 [00061] through p. 24, [00064]) clearly suggest knee implants for repairing knee joints. Additionally, both MCKAY and RICHARDSON teaches the same materials for the bone portion, for example, MCKAY teaches that: “Suitable ceramic materials include, for example, calcium phosphate ceramics such as tricalcium phosphate, hydroxyapatite, and biphasic calcium phosphate. These or other suitable materials can be used to form plug grafts useful in articular cartilage resurfacing procedures. In this regard, such grafts may have a uniform composition throughout, or may vary, for instance having a plug body formed of a first, relatively strong and loadbearing material (e.g. a ceramic, polymer or composite), and a cap formed of another material to provide the articulating surface formed by another material, for example a relatively smooth polymer layer. These and other variants will be apparent to the skilled artisan from the descriptions herein.” ([0051]). And RICHARDSON teaches that: “In a preferred embodiment, the bone scaffold portion may be formed from a mixture of tricalcium phosphate (TCP) and hydroxyapatite (HA).” (p. 7, [0038]).
Applicant particularly argues that: “Based on the aforesaid circumstances and considerations, the disclosure of McKay motivates or suggests to persons of ordinary skill that the bone body of the harvested osteochondral plug suitable for repairing load or weight bearing joints and which resists rotational displacement because it is shaped to have external stabilizing portions, should not be reduced to smaller pieces or particles, even if thereafter reformed and reshaped into a single body, because such size reduction will reduce the mechanical strength of the resulting plug graft and, thereby, increases the risk of damage or failure when implanted into load or weight bearing joints.” And that: “Applicant respectfully asserts that the disclosure of McKay coupled with the general knowledge and understating of persons of ordinary skill in the relevant art teach away from modification of the disclosed osteochondral plug graft, and particularly the single-piece bone body thereof, to produce a graft comprising multiple pieces or particles which, whether alone or reconstituted into a single 3-dimensional body, because such a modified material will have less mechanical strength than the originally harvested single-piece body and, therefore, clearly present increased risk of damage or failure under load bearing conditions after implantation in load or weight bearing joints.” (p. 21, last paragraph through p. 22, first full paragraph).
In response the examiner argues that MCKAY clearly teaches that: “While certain discussions above have focused upon the use of harvested osteochondral plug grafts, in other aspects of the invention, plug grafts of and for use in the invention can be manufactured from other materials or components. Illustratively, plug grafts adapted for receipt in surgical openings in subchondral bone at articular sites, and desirably for integration with the subchondral bone, can be synthesized from natural or synthetic materials. […] Suitable ceramic materials include, for example, calcium phosphate ceramics such as tricalcium phosphate, hydroxyapatite, and biphasic calcium phosphate. These or other suitable materials can be used to form plug grafts useful in articular cartilage resurfacing procedures. In this regard, such grafts may have a uniform composition throughout, or may vary, for instance having a plug body formed of a first, relatively strong and load bearing material (e.g. a ceramic, polymer or composite), and a cap formed of another material to provide the articulating surface formed by another material, for example a relatively smooth polymer layer. These and other variants will be apparent to the skilled artisan from the descriptions herein.” [emphasis added]([0051]). Additionally, MCKAY teaches including growth factors with other materials “Growth factor may be applied to the tissue source in the form of a buffered aqueous solution. Other materials which may be suitable for use in application of the growth factors in the methods and products of the present invention include carrier materials such as collagen, milled cartilage, hyaluronic acid, polyglyconate, degradable synthetic polymers, demineralized bone, minerals and ceramics, such as calcium phosphates, hydroxyapatite, etc., as well as combinations of these and potentially other materials.” [emphasis added]([0055]).
Applicant further argues that (4) “No Reasonable Expectation of Success For Reducing Bone Body to Pieces/Particles Where Cartilage Layer Naturally Attached Thereto When Harvested.” (pp. 15-25). And particularly that: “Applicant submits that use of the terminology "osteochondral" in McKay, to describe embodiments of the plug grafts harvested from mammalian donors, indicates to persons of ordinary skill in the relevant art that the harvested material includes both bone ("osteo'') and cartilage ("chondr''). This interpretation that when the plug graft is an osteochondral plug, it necessarily includes both bone and cartilage which are already naturally attached together is supported throughout the disclosure of McKay.” (p. 22, 4th paragraph). And that: “McKay explains that the disclosed osteochondral plugs useful as plug grafts are harvested from locations of donor bodies where the bone body and cartilage layer are naturally present together and attached to one another. More specifically, paragraph [0034] of McKay states that an osteochondral plug is harvested "from any appropriate structure including hyaline cartilage and underlying subchondral bone" and further explains that "[s]uitable harvest locations in large part occur in weight bearing joints of mammals" (emphasis added). Accordingly, the harvested osteochondral plugs have a bone portion in a single-piece solid form which is shaped to have external contours or a cross-sectional profile other than a circular cylinder, which prevents rotational displacement and increases stability after implanting.”
In response the examiner argues that MCKAY clearly teaches that: “In these regards, it will be understood that while these particular enhanced features can be provided in certain inventive aspects, they are not required in all embodiments or broader features of the present invention.” ([0059]). And that: “While the invention has been illustrated and described in detail in the drawings and foregoing description, the same is to be considered as illustrative and not restrictive in character, it being understood that only the preferred embodiment has been shown and described and that all changes and modifications that come within the spirit of the invention are desired to be protected.” ([0060]). Therefore, one of ordinary skill would have clearly recognized that the scope of the disclosure of MCKAY is broadly encompassing of bone repair materials including an osteochondral repair. Applicant has provided no evidence that the inclusion of pieces, granules, particles, powder, would somehow not work.
Additionally, the examiner argues that Applicants claim is broad and any amount of bone “pieces, granules, particles, powder” would read on the instantly rejected claims. And contrary to Applicants position more likely than not any osteochondral plug graft taken from donor tissue would have included at least some incidental bone “pieces, granules, particles, powder”, therefore Applicants position is not commensurate with the rejected claims, and the scope of the cited prior art. For example, MCKAY teaching that: “Tissue removal can be conducted in any suitable manner including for instance drilling and/or punching, […]. In certain embodiments of the invention as discussed below, the opening for receiving the graft will be created using a drill or punch having a circular cross-section. Multiple, overlapping passes with the drill or punch are made, in order to create an opening having a cross-section defined by multiple, intersecting circular arcs.” ([0039]). Therefore, Applicants argument is not convincing as it is not consistent with the broad disclosure of MCKAY, the ordinary understanding in the prior art, and the scope of the instantly rejected claims.
Conclusion
Claims 2 and 5-12 are pending and have been examined on the merits. Claim 2 is rejected under 35 U.S.C. 112(d)(new ground of rejection); and claims 2 and 5-12 are rejected under 35 U.S.C. 103 (rejection maintained). No claims allowed at this time.
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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
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/IVAN A GREENE/Examiner, Art Unit 1619
/DAVID J BLANCHARD/Supervisory Patent Examiner, Art Unit 1619
1 Of record as cited by Applicants on IDS dated 07/18/2022, Foreign Patent Documents, Citation No. 2.
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