Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined pursuant to the first inventor to file provisions of the AIA .
DETAILED ACTION
Status of the Claims
Receipt of Applicants’ Response, filed 6 November 2025. No claims were amended therein. Claims 60 – 63 and 65 – 71 remain withdrawn as being directed to a non-elected invention. Consequently, claims 56, 58 - 63, 65 – 71, 74, 77, and 79 – 92 are available for active consideration.
REJECTIONS MAINTAINED
Rejections Pursuant to 35 U.S.C. § 103
The following is a quotation of 35 U.S.C. § 103 that 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 rejection of claims 56, 58, 74, 80, 82, 83, 86, and 88 - 92 pursuant to 35 U.S.C. § 103, as being obvious over US 2008/0281431 A1 to Missos, N., published 13 November 2008 (“Missos ‘431”), in view of US 2004/0157798 A1 to Little, D., published 12 August 2004 (“Little ‘798”), and US 2015/0283291 A1 to Vogt, S., claiming priority to 2 April 2014 (“Vogt ‘291”), is hereby maintained.
The Invention As Claimed
Applicant claims a composition comprising an osteoconductive, resorbable biocompatible carrier comprising one or more salts, including calcium sulfate or calcium phosphate, present in amounts of from 40 to 70% wgt of the composition, zoledonic acid in an amount of 0.3 to 200 mg/mL, based on the final volume of the composition, and fosfomycin in an amount of 80 to 200 mg/mL, based on the final volume of the composition, wherein the composition is resorbable, and wherein the composition is in the form of a paste, wherein the composition further comprises a resorbable bone graft material comprising particles of cancellous bone that comprise demineralized bone matrix or fibers, the particles having a particle size of no more than 20 mm, wherein the cancellous bone is allograft and/or autograft, wherein the cancellous bone comprises no more than 10% water and no more than 5% lipids, wherein the composition does not comprise PMMA, wherein the composition comprises at least 110 mg/mL fosfomycin in the final volume of the composition, wherein the fosfomycin is in the form of its calcium salt, and wherein the carrier consists of calcium phosphate, wherein the cancellous bone is allograft and/or autograft, wherein the composition does not comprise polymethylmethacrylate ("PMMA"), wherein the composition comprises fosfomycin in an amount of 110 to 200 mg/mL, based on the final volume of the composition, wherein the fosfomycin is in the form of its calcium salt, wherein the carrier consists of calcium phosphate, wherein the carrier comprises hydroxyapatite, in an amount of 30 to 50% wgt, and the one or more calcium salts hydroxyapatite are present in an amount of 50 to 70% wgt, or 55 to 65% wgt calcium salts, wherein the composition comprises the carrier in an amount of 50 to 70% wgt of the composition, and wherein the zoledronic acid is present in the composition in an amount of from 0.3 to 0.8 mg/mL.
The Teachings of the Cited Art
Missos ‘431 discloses compositions comprising a porous ceramic scaffold having a bioresorbable coating, and a carrier comprising denatured demineralized bone, the ceramic containing a material such as hydroxyapatite, tricalcium phosphate, calcium phosphates, calcium carbonates, calcium sulfates, and combinations thereof (cf. claims 56, 59), the compositions containing a bone material, such as bone powder, bone chips, bone shavings, and combinations thereof, the bioresorbable coating comprising demineralized bone matrix, gelatin, collagen, hyaluronic acid, chitosan, polyglycolic acid, polylactic acid, polypropylene fumarate, polyethylene glycol, and mixtures thereof (see Abstract; see also ¶[0005]; cf. claim 58), wherein exemplary ceramic materials include those sold under the trade name ProOsteon, such as ProOsteon®200 and ProOsteon®500, by and Calcigen® (see ¶[0024]), wherein the bone repair compositions comprise from about 5% to about 60% of the ceramic scaffolds, by weight, and from about 30% to about 95% of the bioresorbable material, by weight (see ¶[0027]), wherein the carrier comprises from about 0.2% to about 40% of denatured demineralized bone, by weight of the carrier, the remainder of the carrier comprising an aqueous solution, such as water or saline (see ¶[0028]), wherein once bone is obtained, the bone is milled into particles ranging from about 100 microns to about 2000 microns (see ¶[0030]), wherein from about 5 to about 25 grams, or from about 10 to about 20 grams, of demineralized bone is added per 100 grams of water or a saline solution (see ¶[0033]), wherein the disclosed compositions contain a bone material from cortical, cancellous, and/or corticocancellous bone from a human or other animal, the bones being allogenic or autologous, with about 100 grams of the carrier mixed with from about 25 to about 45 grams of the bone material (see ¶[0035]), wherein the composition can also include other materials such as isolated tissue materials, bioactive agents, and combinations thereof (see ¶[0039]), wherein the bioactive agents include those that provide a therapeutic, nutritional, or cosmetic benefit, including repairing unhealthy or damaged tissue, minimizing infection at a treatment site, increasing integration of healthy tissue into the composition, and preventing disease or defects in healthy or damaged tissue, including antibiotics and other anti-infective agents (see ¶[0040]), wherein a moldable composition formed by mixing a coated ceramic scaffold with the carrier to form a paste, or moldable material, which process can be performed in a mold for making a formed composition (see ¶[0051]), and wherein the moldable composition is dried to remove moisture (see ¶[0052]). The reference does not disclose a bone repair composition that comprises zoledronic acid, as a bioactive material, at 0.3 to 200 mg/mL of the composition, and fosfomycin, as an antibiotic, at 80 – 200 mg/mL, or a composition comprising cancellous bone that has a water content of no more than 10%, and a lipid content of no more than 5%. The teachings of Little ‘798 and Vogt ‘291 remedy those deficiencies.
Little ‘798 discloses both a drug, and a method of bone grafting, which improve the osteoinductive and/or osteoconductive potential of bone grafts, bone graft substitutes, and/or extenders, wherein the drug is a bisphosphonate [ZA] (see Abstract), wherein the extender/bone graft substitutes are preferably any material (other than an autogenous bone graft) that is provided in order to increase the amount of graft material for implantation or injection into a graft site (see ¶[0008]), wherein the extenders are preferably synthetic calcium complexes, such as a tricalcium phosphate cement marketed as NORIAN® SRSTM (see ¶[0010]), wherein the product is resorbed in vivo, which is preferred (see ¶[0044]), although that resorption may be incomplete, but results in no clinical consequences in that the osteointegrated product is biocompatible (see ¶[0044]), wherein various bone promoting growth factors can be included in a demineralized bone matrix as provided in a delivery medium in the form of a gel, putty, sheet, or other forms, wherein the demineralized bone still contains some of the mediators implicated in bone healing and is typically taken from allografts (human bone from a cadaver, processed such that infective agents are eliminated) or xenografts (bone or other tissue from an animal source), which grafts have had the calcium content removed (demineralized), leaving many of the gene products (proteins) known to upregulate bone formation in the graft substitute (see ¶[0011]), wherein, alternatively, refined human gene products such as Bone Morphogenetic Protein 7 (OP-1), Bone Morphogenetic Protein 2, and other Bone Morphogenetic proteins (BMPs) are available, as well as other products using transforming growth factor beta (TGF-β), Fibroblast Growth Factor (FGF), and Insulin-like Growth factor (IGF) (see ¶[0013), wherein bisphosphonate drugs in certain dose ranges have properties conducive to bone formation, whilst minimally interfering with resorption and remodeling of a bone (see ¶[0017]), wherein the bone graft may also include allograft (human bone from a cadaver which is processed such as to remove any infectious agents), or xenograft (bone from an animal source) (see ¶[0043]), wherein an extender may be mixed with other pharmacologically active substances, such as antibiotics (see ¶[0045]), wherein at least one bisphosphonate is mixed with the bone graft, or bone graft substitute, or extender, or mixture thereof, prior to a bone grafting procedure and the mixture administered to the graft site (see ¶[0049]), wherein the bisphosphonate is zoledronic acid (zoledronate, 1-hydroxy-2-[(lH-imidazol-1-yl)ethylidine]-bisphosphonic acid (see ¶[0055]), wherein the amount of bisphosphonate in the manufactured bone graft substitute or extender is such that new host bone formation is enhanced without substantially interfering with the gradual resorption of the said bone graft substitute or extender (or, when used in conjunction with bone graft, the bone graft), such that the bone graft substitute, extender, or bone graft, together with any carrier medium, is completely resorbed and replaced by normal, remodeled host bone in the long term (see ¶[0051]), wherein a bone substitute, or an extender, or combinations thereof [NORIAN® SRSTM/calcium phosphates], is mixed at 0.0001 to 0.5 mg/kg body weight per dose of zoledronic acid (zoledronate) (see ¶[0051]; see also ¶[0101]), and wherein the bone graft, bone graft substitute, extender, or a combination thereof, in addition to being mixed with an effective amount of a bisphosphonate, may be further mixed with a carrier medium such as collagen, gelatin, glycerol, resin, polyglycolic acid, polylactic acid, or any other fully resorbable biocompatible medium, or a combination thereof (see ¶[0103]).
Vogt ‘291 discloses a bone cement powder that comprises a fosfomycin preparation (see Abstract), wherein the fosfomycin is the monohydrate of the calcium salt of fosfomycin (CAS 26016-98-8), referred to as calcium-fosfomycin monohydrate (see ¶[0022]), wherein the fosfomycin preparation is a solid preparation, preferably present as a powder (see ¶[0027]), wherein the fraction of the fosfomycin preparation present in the bone cement powder is 1 to 20% by weight, based on the total weight of the bone cement powder (see ¶[0039]), and wherein the fosfomycin is mixed with the bone cement powder, and a plastically deformable dough is obtained by mixing the powders with a liquid component (see ¶[0044]).
Application of the Cited Art to the Claims
It would have been prima facie obvious before the filing date of the claimed invention to prepare compositions comprising a porous ceramic scaffold having a bioresorbable coating, and a carrier comprising denatured demineralized bone, the ceramic containing a material such as hydroxyapatite, tricalcium phosphate, calcium phosphates, calcium carbonates, calcium sulfates, and combinations thereof, the compositions also containing a bone material, such as bone powder, bone chips, bone shavings, and combinations thereof, the bioresorbable coating comprising demineralized bone matrix, wherein the compositions comprise from about 5% to about 60% of the ceramic scaffolds, by weight, and from about 30% to about 95% of the bioresorbable material, by weight, wherein the carrier comprises from about 0.2% to about 40% of denatured demineralized bone, by weight of the carrier, the remainder of the carrier comprising an aqueous solution, such as water or saline, wherein, once bone is obtained, the bone is milled into particles ranging from about 100 microns to about 2000 microns, wherein the disclosed compositions contain a bone material from cortical, cancellous, and/or corticocancellous bone from a human or other animal, the bones being allogenic or autologous, wherein the composition can also include other materials such as bioactive agents, wherein the bioactive agents include those that provide a therapeutic benefit, including repairing unhealthy or damaged tissue, minimizing infection at a treatment site, increasing integration of healthy tissue into the composition, and preventing disease or defects in healthy or damaged tissue, the bioactive agents including antibiotics and other anti-infective agents, wherein a moldable composition is formed by mixing the coated ceramic scaffold with the carrier to form a paste, or moldable material, and wherein the moldable composition is dried to remove moisture, as taught by Missos ‘431, wherein the compositions, in addition to comprising a porous ceramic scaffold and a carrier comprising denatured demineralized bone, further comprise a bisphosphonate, such as zoledronic acid (zoledronate, 1-hydroxy-2-[(lH-imidazol-1-yl)ethylidine]-bisphosphonic acid as the bioactive agent, wherein bisphosphonate drugs in certain dose ranges have properties conducive to bone formation, whilst minimally interfering with resorption and remodeling of a bone, wherein the amount of bisphosphonate in the compositions is such that new host bone formation is enhanced without substantially interfering with the gradual resorption of the ceramic and bone materials, as taught by Little ‘798, wherein the compositions further comprise
the monohydrate of the calcium salt of fosfomycin as the antibiotic, wherein the fraction of the fosfomycin preparation is in a bone cement composition at from 1 to 20% by weight, based on the total weight of the composition, as taught by Vogt ‘291. One of ordinary skill in the art would be motivated to do so, with a reasonable expectation of success in so doing, by the express teachings of Little ‘798 to the effect that bisphosphonate drugs in specific dose ranges have properties conducive to bone formation, while minimally interfering with resorption and remodeling of a bone (see ¶[0017]), and by the teachings of Vogt ‘291 that fosfomycin acts against a wide spectrum of bacteria, including both gram-negative and gram-positive bacteria, such as methicillin-resistant staphylococci.
With respect to those claims reciting quantitative limitations directed to relative contents of various components in the compositions of the inventive compositions, the Examiner notes that the loadings taught in the cited references are not exactly congruent with the claim limitations. However, it is the Examiner’s position that the cited art teaches a range of loadings of these components that significantly overlap with the claimed loadings and, as such, would render the claimed invention obvious. See MPEP § 2144.05. “In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976).”
With respect to the limitations recited in claims 56 and 58, directed to the bone reconstruction compositions being “curable,” the Examiner notes that the cited references do not use that term in describing the functioning of the disclosed implant compositions. However, the Examiner further notes that the moldable composition disclosed in Missos ‘431 is dried to remove moisture (see ¶[0052]). It is the Examiner’s position that this drying to solidity can be reasonably be read to meet this limitation. In addition, or in the alternative, the Examiner further notes that Little ‘798 discloses use of a composition comprising calcium salts [carrier in Applicant’s terminology] (NORIAN® SRSTM), that after injection into a bone repair site, “harden” within ten minutes of implantation in vivo. It is the Examiner’s position that one of ordinary skill in the art would recognize that the hardening disclosed in the cited references is the “curing” recited in the claims.
With respect to claim 80, which claim recites a limitation directed to the compositions of the invention not comprising polymethylmethacrylate (PMMA), the Examiner notes that Missos ‘431 and Little ‘798 do not disclose the use of components comprising PMMA. In this regard, the Examiner further notes that, although Vogt ‘291 discloses compositions comprising fosfomycin and PMMA, the rejection cites to this reference solely on the basis of its teachings related to fosfomycin, and not for disclosures relating to the use of compositions comprising fosfomycin and PMMA.
With respect to claims 82 and 84, which claims recite limitations directed to the composition of the invention comprising at least 110 mg/mL fosfomycin in the final volume of the composition, the Examiner notes that the cited references do not expressly disclose bone repair compositions wherein the fosfomycin content is expressed in such terms. However, the Examiner also notes that Vogt ‘291 teaches that the fraction of fosfomycin present in the disclosed bone repair compositions is 1 to 20% by weight, based on the total weight of the bone cement powder (see ¶[0039]). It is the Examiner’s position that preparing bone repair compositions with fosfomycin contents within the disclosed range would necessarily encompass the claimed ranges, particularly in light of the teaching that the powder components of the compositions disclosed in Vogt ‘291 are mixed with a liquid component, the amount of fluid varied as a function of the desired form of the composition, whether with a dough consistency (less fluid), or more fluid (lower viscosity for injection). In addition, or in the alternative, adjusting or varying the preparation conditions to achieve water and lipid contents within the claimed ranges would amount to nothing more than an optimization of a result-effective variable, the exercise of which is well with the expertise of one of ordinary skill in the appropriate art. Consequently, in the absence of evidence as to the criticality of such parameter, this limitation cannot support patentability. See MPEP § 2144.05 II. A.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by claims 56, 58, 74, 80, 82, 83, 86, and 88 - 92 would have been obvious within the meaning of 35 USC § 103.
The rejection of claims 59, 79, 81, 84, 85, and 87 pursuant to 35 U.S.C. § 103, as obvious over Missos ‘431, Little ‘798, and Vogt ‘291, as applied above to claims 56, 58, 74, 80, 82, 83, 86, and 88 - 92, and further in view of US 9,579,421 to Bhat, A., et al., claiming priority to 7 February 2014 (“Bhat ‘421”), is hereby maintained.
The Invention As Claimed
Applicant claims a kit-of-parts comprising, in a first part, an osteoconductive, resorbable biocompatible carrier comprising one or more calcium salts, including calcium sulfate or calcium phosphate, wherein the carrier is present in an amount of 40 to 70% wgt of the composition, zoledronic acid in an amount of 0.3 mg/mL to 200 mg/mL, based on the final volume of the composition, and fosfomycin in an amount of 80 mg/mL to 200 mg/mL, based on the final volume of the composition, and, in a second part, a biocompatible matrix comprising particles of cancellous bone, wherein the cancellous bone comprises demineralized bone matrix or fibers, and wherein the particles of the biocompatible matrix have a particle size of no more than 20 mm, wherein the cancellous bone comprises no more than 10% water and no more than 5% lipids, wherein the parts are capable of forming a paste when mixed, wherein the composition does not comprise polymethylmethacrylate ("PMMA"), wherein the composition comprises fosfomycin in an amount of 110 to 200 mg/mL, based on the final volume of the composition, wherein the fosfomycin is in the form of its calcium salt, and wherein the carrier consists of calcium phosphate.
The Teachings of the Cited Art
The teachings of Missos ‘431, Little ‘798, and Vogt ‘291 are relied upon as set forth in the above rejection of claims 56, 58, 74, 80, 82, 83, 86, and 88 - 92. The references do not disclose a kit-of-parts comprising, in a first part, an osteoconductive, resorbable biocompatible carrier comprising one or more calcium salts, including calcium sulfate or calcium phosphate, wherein the carrier is present in an amount of 40 to 70% wgt of the composition, zoledronic acid in an amount of 0.3 mg/mL to 200 mg/mL, based on the final volume of the composition, and fosfomycin in an amount of 80 – 200 mg/mL or 110 – 200 mg/mL to 200 mg/mL, based on the final volume of the composition, and, in a second part, a biocompatible matrix comprising particles of cancellous bone, wherein the cancellous bone comprises demineralized bone matrix or fibers, and wherein the particles of the biocompatible matrix have a particle size of no more than 20 mm, or a kit comprising a composition that does not comprise PMMA, or wherein the fosfomycin is in the form of the calcium salt. These deficiencies are addressed by the teachings of Bhat ‘421.
Bhat ‘421 discloses bone grafts, as well as products and kits including the bone grafts, wherein the grafts comprise osteogenic stem cells in a mix of osteoinductive demineralized bone matrix and osteoconductive cortico-cancellous chips (see Abstract), wherein the bone grafts include moldable and shapeable putty compositions used for filling bone defects (see Col. 4, ll. 65 – 67), wherein the cortical and cancellous bone material is obtained from long bones, such as femur, tibia, radius, and ulna (see Col. 7, ll. 3 -4), wherein condyles, separated from the cortical component of the bones, are milled using a bone mill to produce cancellous bone chips in the range of 0.05 – 1.5 mm (see Col. 7, ll. 14 – 15), wherein the kits include one or more of the bone grafts or one or more components or ingredients thereof, such as the bone grafts, along with instructions and/or at least one additional component (such as devices, implants, tools) that may be used for example in the storage, preparation or use of the bone graft substitutes (see Col. 5, ll. 24 – 31), and wherein the kits may include cortical and/or cancellous chips in any of the disclosed stages of preparation, and/or other ingredients of the present bone grafts, which may be combined, mixed or treated in order to form the bone grafts (see Col. 5, ll. 51 – 55).
Application of the Cited Art to the Claims
It would have been prima facie obvious before the filing date of the claimed invention to prepare a bone graft composition according to the teachings of Missos ‘431, Little ‘798, and Vogt ‘291, wherein the composition is available in the form of a kit that includes one or more of the bone grafts or one or more components or ingredients thereof, such as the bone grafts, along with instructions and/or at least one additional component (such as devices, implants, tools, etc.) that may be used for example in the storage, preparation or use of the bone graft substitutes (see Col. 5, ll. 24 – 31), and wherein the kits may include cortical and/or cancellous chips in any of the disclosed stages of preparation, and/or other ingredients of the present bone grafts, which may be combined, mixed or treated in order to form the bone grafts, as taught by Bhat ‘421. One of ordinary skill in the art would be motivated to do so, with a reasonable expectation of success in so doing by the teachings of Bhat ‘421 to the effect that the kit components are used to assist in adding the bone graft to a device or implant, or to assist in inserting the bone graft into a mammal (see ¶[0039]).
With respect to claim 79, which claim recites limitations directed to cancellous bone particles with a water content of no more than 10%, and a lipid content of no more than 5%, the Examiner notes that Bhat ‘421 discloses multiple processes for treating/preparing the cancellous bone chips before incorporation into the bone grafts that include multiple treating, rinsing, freezing and drying steps. It is the Examiner’s position that subjecting the cancellous bone chips to such processes would necessarily result in the chips having water and lipid contents reading on the claimed ranges. In addition, or in the alternative, adjusting or varying the preparation conditions to achieve water and lipid contents within the claimed ranges would amount to nothing more than an optimization of a result-effective variable, the exercise of which is well with the expertise of one of ordinary skill in the appropriate art. Consequently, in the absence of evidence as to the criticality of such parameter, this limitation cannot support patentability. See MPEP § 2144.05 II. A.
With respect to claim 81 , which claim recites a limitation directed to the compositions of the invention not comprising polymethylmethacrylate (PMMA), the Examiner notes that Missos ‘431, Little ‘798, Vogt ‘291, and Bhat ‘421 do not disclose the use of compositions comprising PMMA. In this regard, the Examiner further notes that, although Vogt ‘291 discloses compositions comprising fosfomycin and PMMA, the rejection cites to this reference on the basis of its teachings related to fosfomycin, and not for disclosures relating to the use of compositions comprising fosfomycin and PMMA.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by claims 59, 79, 81, 84, 85, and 87 would have been obvious within the meaning of 35 USC § 103.
The rejection of claim 77 pursuant to 35 U.S.C. § 103, as obvious over Missos ‘431, Little ‘798, and Vogt ‘291, as applied above to claims 56, 58, 74, 80, 82, 83, 86, and 88 - 92, and further in view of US 8,702,809 B2 to Nauman, E. and D. Dickerson, claiming priority to 14 September 2007 (“Nauman ‘809”), is hereby maintained.
The Invention As Claimed
The invention with respect to claim 58 has been described above. In addition, Applicant claims a bone repair composition wherein the cancellous bone of the matrix is vascularized.
The Teachings of the Cited Art
The teachings of Missos ‘431, Little ‘798, and Vogt ‘291 are relied upon as set forth in the above rejection of claims 56, 58, 74, 80, 82, 83, 86, and 88 – 92. The references do not disclose a bone repair composition comprising a matrix of particles of allograft cancellous bone that are vascularized. The teachings of Nauman ‘809 remedy that deficiency.
Nauman ‘809 discloses a cancellous bone scaffold (see Abstract), wherein the scaffold can comprise a demineralized bone segment possessing a calcium content of about 2%, or less (see Col. 2, ll. 29 – 36), wherein autografts are preferred due to their biocompatibility and lowered risk for disease transmission (see Col. 1, ll. 20 – 21), wherein cancellous bone scaffolds provide advantages over prior art scaffolds of cortical bone in that cancellous bone can vascularize much more easily due to the fact that cortical bone is the dense surface layer of the bone having little vascularization, while cancellous bone is a spongy material that makes up the bulk of the interior of bones and has a low density and strength, but very high surface area (see Col. 3, ll. 34 – 43).
Application of the Cited Art to the Claims
It would have been prima facie obvious before the filing date of the claimed invention to prepare a bone graft composition according to the teachings of Missos ‘431, Little ‘798, and Vogt ‘291, wherein the composition comprises a matrix comprising particles of autograft cancellous bone, and wherein the autograft is vascularized, according to Nauman ‘809. One of ordinary skill in the art would have been motivated to do so, with a reasonable expectation of success in so doing, by the express teachings of Lee ‘417 to the effect that bone implants comprising cancellous bone are more readily integrated with native bone after implantation (see ¶[0006]), and by the teachings of Nauman ‘809 to the effect that cancellous bone can vascularize much more easily than cortical bone due to its porosity.
The Examiner notes that claim 77 recites a limitation directed to the cancellous autograft being “vascularized.” It is the Examiner’s position that one of ordinary skill in the relevant art would recognize that a bone reconstruction composition, particularly ex vivo, could not be vascularized as prepared for implantation. Consequently, the Examiner is interpreting the limitation in question as being directed to cancellous bone that is capable of being vascularized once implanted into a host patient.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by claim 77 would have been obvious within the meaning of 35 USC § 103.
Response to Applicant’s Arguments
The Examiner has considered Applicant’s arguments filed 6 November 2025, but does not find them persuasive. Applicants first argues that “the combination of Missos, Little, and Vogt fails to disclose or suggest a curable bone reconstruction composition comprising said osteoconductive, resorbable biocompatible carrier comprising one or more calcium salts and ‘fosfomycin or a fosfomycin salt in an amount of 80 mg/ml to 200 mg/ml, wherein ml refers to the final volume of the composition,’ as required by claim 56,” on the basis that the cited references fail to disclose compositions comprising fosfomycin “in an amount of 80 mg/ml to 200 mg/ml.” The Examiner respectfully disagrees.
First of all, Applicant’s argument once again rests primarily on alleged (and, in most cases, acknowledged) deficiencies in the disclosures of the cited references. Not only is this logical approach improper (see In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986), but also Applicant’s argument fails to take into consideration the logical structure of the rejection of record. In this regard, the Examiner first notes that there is no single reference that discloses compositions comprising both fosfomycin an zoledronic acid, which is one of the major reasons that the rejection is formulated as an obviousness rejection, rather than as an anticipation rejection, but that in no way impacts the validity of the rejection.
The primary reference, Missos ‘531, is cited for its teachings directed to the general form of the bone repair composition, that form comprising a porous ceramic scaffold and a carrier that comprises denatured demineralized bone, the ceramic containing calcium phosphates, calcium carbonates, calcium sulfates, and combinations thereof, as well as bioactive agents, including antibiotics, wherein the bioactive agents include those that provide a therapeutic benefit, including for the repair of unhealthy or damaged tissue, the agents minimizing infection at a treatment site, increasing integration of healthy tissue into the composition, and preventing disease or defects in healthy or damaged tissue, including antibiotics, all goals that one of ordinary skill in the relevant art would recognize as common for bone repair compositions. The reference does not disclose fosfomycin as the antibiotic, nor zoledronic acid as an additional therapeutic agent. The rejection cites to Little ‘798 for its teachings regarding the utility of zoledronic acid in bone repair compositions; likewise, the rejection cites Vogt ‘291 for its teaching that fosfomycin exhibits utility in bone cements used for repair of bone defects. Thus, one of ordinary skill in the art would be motivated to use the teachings of the secondary references to modify the construct of Missos ‘431 to include zoledronic acid and fosfomycin to enhance the bone repair capabilities of the compositions disclosed in that reference.
With respect to the loadings of zoledronic acid and fosfomycin, the references not only disclose suggested loadings for each of the therapeutic agents, but also provide guidance to the skilled practitioner, for example, that the amount of a bisphosphonate, such as zoledronic acid, in the a bone graft substitute or extender should be such that new host bone formation is enhanced without substantially interfering with the gradual resorption of the said bone graft substitute or extender (or, when used in conjunction with bone graft, the bone graft), so that the bone graft substitute, extender, or bone graft, together with any carrier medium, is completely resorbed and replaced by normal, remodeled host bone in the long term (see Little ‘798, at ¶[0051]). Although not explicitly disclosing loadings reading on the claim limitations, it is the Examiner’s position that the amount of experimentation needed to reach such clinically significant results is well within the expertise of one of ordinary skill in the art.
With respect to Applicant’s arguments based on Vogt ‘291 disclosing the use of fosfomycin in PMMA-based bone cements, Applicant is reminded that the rejection relies on the teachings of the reference for disclosing the utility of fosfomycin in bone repair, and not for the type of bone repair composition in which the antibiotic is used.
Applicant further cites to the inventor’s affidavits, specifically stating that “the relative amounts of fosfomycin described by Vogt still would not achieve the necessary curing time that is to be a practical and usable curable bone reconstruction composition according to claim 56 (emphasis added).” In this regard, the Examiner notes that the feature upon which Applicant relies (i.e., curing time) is not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Furthermore, the fact that Applicant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). In this regard, Applicants are reminded that the invention as claimed is directed to a composition of matter, and that, as a consequence, the reasons for combining the teachings of cited references, are not necessarily controlling to the patentability of the compositions, as claimed. The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006).
With respect to the additional rejections, Applicant relies on the arguments addressed above relating to the primary rejection. However, in light of the above discussion, these arguments are not persuasive.
Consequently, claims 56, 58 - 63, 65 – 71, 74, 77, and 79 – 92 stand rejected pursuant to 35 U.S.C. § 103.
NO CLAIM IS ALLOWED.
THIS ACTION IS MADE FINAL. Applicants are reminded of the extension of time policy as set forth in 37 CFR § 1.136(a).
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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 Response 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 mailing date of this Final Action.
CONCLUSION
Any inquiry concerning this communication or any other communications from the Examiner should be directed to Daniel F. Coughlin whose telephone number is (571)270-3748. The Examiner can normally be reached on M - F 8:30 a.m. - 5:00 p.m.
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 an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see <http://pair-direct.uspto.gov>. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
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.
/DANIEL F COUGHLIN/
Examiner, Art Unit 1619
/DAVID J BLANCHARD/ Supervisory Patent Examiner, Art Unit 1619