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
The Examiner acknowledges receipt of Applicants’ Response, filed 29 June 2026. No claims are amended therein. Upon finalization an entry of the Requirement for Election of Species (see below), claims 31, 33 – 39, 41, 42, and 44 – 55 will be available for substantive consideration.
Response to Restriction/Election
The Examiner acknowledges Applicants’ election, without traverse, of the species calcium phosphate from the genus of bone scaffold material, and the species spine fusion from the genus of site of bone fusion. In the Response, Applicants stated that “[a]t least claims 31, 33, 39, and 41 – 55 read on the elected species.” However, the Examiner notes that claim 43 recites that “the bone scaffolding material comprises calcium phosphate and calcium sulfate.” Given that Applicants have elected calcium phosphate as the bone scaffolding material and claim 43 is directed to a combination of calcium phosphate and calcium sulfate, the claim is reasonably read to be directed to a non-elected species. Consequently, claims is hereby withdrawn from further consideration pursuant to 37 CFR § 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 31, 33 – 39, 41, 42, and 44 – 55 are under consideration to the extent that the bone scaffolding material is calcium phosphate, and the site of bone fusion is the spine.
Rejections Pursuant to 35 U.S.C. § 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.
Claims 54 and 55 are rejected pursuant to 35 U.S.C. § 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention. The claims, dependent from claim 31, recite limitations directed to “the biocompatible binder.” There is insufficient antecedent basis for this limitation in the claims. Appropriate correction or cancellation of the claims is required.
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.
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 absent any evidence to the contrary. Applicants are advised of the obligation pursuant to 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.
Claims 31, 33, 34, 38, 39, 41, 42, and 44 – 55 are rejected pursuant to 35 U.S.C. § 103, as being obvious over US 2010/0183515 A1 to Hart, C., et al., published 22 July 2010 (“Hart ‘515”).
The Invention As Claimed
Applicants claim a method for fusing bone comprising administering a composition comprising a solution of platelet-derived growth factor (PDGF) disposed in a biocompatible matrix comprising calcium phosphate as a bone scaffolding material, and collagen, wherein the solution has a PDGF concentration ranging from about 0.05 mg/mL to about 5 mg/mL, and wherein the solution and the biocompatible matrix are present in the composition in a volume to mass ratio (mL:g) ranging from about 1.5 : 1 to about 2.5 : 1, wherein the site of bone fusion is in a spine, wherein the spine fusion procedure is an interbody fusion procedure, wherein the spine fusion procedure is a lumbar fusion procedure, wherein the volume to mass ratio (mL/g) is about 2 : 1, wherein the calcium phosphate comprises β-tricalcium phosphate (β-TCP), wherein 44/the PDGF is present in the solution at a concentration ranging from about 0.1 mg/mL to about 1.0 mg/mL, or at a concentration of 0.3 mg/mL, wherein the PDGF comprises PDGF-BB, wherein 47/the PDGF-BB is recombinant human (rh)PDGF-BB, wherein the solution comprises PDGF in a buffer, such as a sodium acetate buffer, wherein the bone scaffolding material comprises particles in a range of about 100 µm to about 5000 µm in size, wherein the porosity of the bone scaffolding material is greater than about 80%, wherein the bone scaffolding material comprises interconnected pores, wherein the bone scaffolding material is resorbable, wherein the biocompatible binder is present in the biocompatible matrix in an amount ranging from about 15% wgt to about 25%, or at about 20% wgt.
The Teachings of the Cited Art
Hart ‘515 discloses compositions and methods useful for treating structures of the vertebral column, including vertebral bodies, the method comprising providing a composition comprising a PDGF solution and a biocompatible matrix and applying the composition to at least
one vertebral body (see Abstract), wherein minimally invasive treatments for vertebral body compression fractures, vertebroplasty and kyphoplasty, have been developed to address the issues of pain and fracture stabilization, wherein vertebroplasty is the filling of a fractured vertebral body with the goals of stabilizing the bone, preventing further collapse, and eliminating acute fracture pain; however, vertebroplasty does not attempt to restore vertebral height and/or sagittal alignment (see ¶[0007]), wherein kyphoplasty is a minimally invasive surgical procedure with the goal of safety, improving vertebral height and stabilizing vertebral compression fractures (VCF), with the procedure, an inflatable bone tamp, guided by x-ray images, is inflated in the fractured vertebral body, compacting the inner cancellous bone as it pushes the fractured cortices back toward their normal position, allowing fixation to then be done by filling the void with a biomaterial under volume control with a more viscous cement (see ¶[0008]), wherein a composition for promoting bone formation in a vertebral body comprises a solution comprising
platelet derived growth factor (PDGF), and a biocompatible matrix, wherein the PDGF is absorbed into the biocompatible matrix (see ¶[0012]), wherein the PDGF is present in the solution in a concentration ranging from about 0.01 mg/mL to about 10 mg/mL (see ¶[0013]), wherein the PDGF comprises PDGF homodimers and heterodimers, such as PDGF-BB, including recombinant human PDGF-BB (rhPDGF-BB) (see ¶[0014]), wherein the biocompatible matrix comprises a bone substituting agent (also referred to as a scaffolding material herein), such as β-tricalcium phosphate (β-TCP) and, optionally, a biocompatible binder (see ¶[0014]), wherein the biocompatible binder comprises collagen, such as bovine collagen (see ¶[0018]), wherein methods for promoting or accelerating bone formation in a vertebral body comprise providing a composition comprising a PDGF solution disposed in a biocompatible matrix and applying an effective amount of the composition to at least one vertebral body by injecting the composition into the at least one vertebral body (see ¶[0023]), wherein the composition can be applied to a second vertebral body, in some instances an adjacent vertebral body, subsequent to a vertebroplasty or kyphoplasty of a first vertebral body (see ¶[0024]), wherein “high risk vertebral bodies” (HVB) refer to vertebral bodies of vertebrae T5 through T12, as well as L1 through L4 (see ¶[0025]), wherein solutions comprising PDGF are formed by solubilizing PDGF in one or more buffers, such as a sodium acetate buffer (see ¶[0052]), wherein the solution comprising PDGF has a pH ranging from about 5.0 to about 8.0 (see ¶[0054]), wherein the bone scaffolding material has multidirectional and interconnected porosity with pores of varying diameters (see ¶[0059]), with pore diameters ranging from about 1 µm to about 1 mm (see ¶[0064]), with total porosities greater than about 90% (see ¶[0065]), wherein the bone scaffolding material comprises a plurality of particles (see ¶[0066]), having average diameters ranging from about 1 µm to about 5 mm (see ¶[0067]), wherein the bone scaffolding materials are moldable, extrudable and/or injectable (see ¶[0068]), wherein the bone scaffolding materials are bioresorbable (see ¶[0069]), wherein biocompatible binders, such as collagen, comprise materials operable to promote cohesion between combined substances, promoting adhesion between particles of a bone scaffolding material in the formation of a biocompatible matrix (see ¶[0077]), wherein the biocompatible collagen binder can be present in a biocompatible matrix in an amount ranging from about 5% wgt to about 50% wgt of the matrix (see ¶[0081]), wherein the biocompatible matrix in the form of a paste or putty can comprise particles of a bone scaffolding material adhered to one another by a biocompatible binder (see ¶[0082]), wherein the paste or putty can harden subsequent to implantation, thereby reducing matrix flowability and moldability (see ¶[0084]), wherein the collagen binder can comprise any type of collagen, including Type I, Type II, and Type III collagens (see ¶[0088]), wherein the biocompatible matrix comprising β-TCP particles and a collagen binder can comprise macropores having diameters ranging from about 100 µm to about 1 mm, or greater, mesopores having diameters ranging from about 10 µm to 100 µm, and micropores having dian1eters less than about 10 µm (see ¶[0091]), wherein vertebral bodies comprise thoracic vertebral bodies, lumbar vertebral bodies, or combinations thereof, or cervical vertebral bodies (see ¶[0111]), and wherein, in an exemplified embodiment, a ratio of about 3 mL of rhPDGF-BB solution to about 1 g dry weight of the (β-TCP/collagen biocompatible matrix) was used to produce the composition, and the rhPDGF-BB solution was expelled on the biocompatible matrix with a syringe, and the resulting composition was blended into a paste for placement into a syringe for subsequent injection into a vertebral body (see Ex. 1, ¶[0119]).
Application of the Cited Art to the Claims
It would have been prima facie obvious before the filing date of the claimed invention to
treat structures of the vertebral column, including vertebral bodies, by a method comprising providing a composition comprising a PDGF solution and a biocompatible matrix and applying the composition to at least one vertebral body, wherein a composition that promotes bone formation in a vertebral body comprises a solution of platelet derived growth factor (PDGF), and a biocompatible matrix, wherein the PDGF is absorbed into the biocompatible matrix, wherein the PDGF is present in the solution in a concentration ranging from about 0.01 mg/mL to about 10 mg/mL, wherein the PDGF comprises PDGF homodimers and heterodimers, such as PDGF-BB, including recombinant human PDGF-BB (rhPDGF-BB), wherein the biocompatible matrix comprises β-tricalcium phosphate (β-TCP) and collagen as a binder, wherein the methods for promoting or accelerating bone formation in a vertebral body comprise injecting the composition into the at least one vertebral body, wherein the vertebral body is positioned in the vertebrae of T5 through T12, as well as L1 through L4, wherein solutions comprising PDGF comprise one or more buffers, such as sodium acetate buffers, to maintain the pH of the solution in the range from about 5.0 to about 8.0, wherein the bone scaffolding material has multidirectional and interconnected porosity with pores of varying diameters, with pore diameters ranging from about 1 µm to about 1 mm, with total porosities greater than about 90%, wherein the β-TCP bone scaffolding material comprises a plurality of particles, having average diameters ranging from about 1 µm to about 5 mm, wherein the bone scaffolding materials are moldable, extrudable and/or injectable, wherein the bone scaffolding materials are bioresorbable, wherein the biocompatible collagen binder can be present in a biocompatible matrix in an amount ranging from about 5% wgt to about 50% wgt of the matrix, wherein the composition in the form of a paste or putty can harden subsequent to implantation, wherein the collagen binder can comprise any type of collagen, including Type I, Type II, and Type III collagens, wherein vertebral bodies comprise thoracic vertebral bodies, lumbar vertebral bodies, or cervical vertebral bodies, or combinations thereof, and wherein, in an exemplified embodiment, a ratio of about 3 mL of rhPDGF-BB solution to about 1 g dry weight of the (β-TCP/collagen biocompatible matrix) was used to produce the composition, and the rhPDGF-BB solution was expelled on the biocompatible matrix with a syringe, and the resulting composition was blended into a paste for placement into a syringe for subsequent injection into a vertebral body, as taught by Hart ‘515. 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 the reference to the effect that the disclosed methods provide for improving the stability of damaged or degenerated vertebral discs and, at the same time providing for growth of new bone at the site of implantation.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by claims 31, 33, 34, 38, 39, 41, 42, and 44 – 55 would have been obvious within the meaning of 35 USC § 103.
Claims 35 – 37 are rejected pursuant to 35 U.S.C. § 103, as being obvious over Hart ‘515, as applied in the above rejection of claims 31, 33, 34, 38, 39, 41, 42, and 44 – 55, and further in view of US 2008/0045949 A1 to Hunt, M., et al., published 21 February 2008 (“Hunt ‘949”).
The Invention As Claimed
Applicants claim a method for fusing bone comprising administering a composition comprising a solution of platelet-derived growth factor (PDGF) disposed in a biocompatible matrix comprising calcium phosphate and collagen, wherein the method further comprises the steps of placing an intravertebral spacer between vertebral bodies, disposing the composition in the vertebral spacer prior to placing the vertebral spacer between the vertebral bodies, and disposing the composition in the spacer after placing the spacer between the vertebral bodies.
The Teachings of the Cited Art
The teachings of Hart ‘515 are relied upon as set forth in the above rejection of claims 31, 33, 34, 38, 39, 41, 42, and 44 – 55. The reference does not disclose a method fusing bone in the spine comprising the steps of placing an intravertebral spacer between vertebral bodies, disposing the composition in the vertebral spacer prior to placing the vertebral spacer between the vertebral bodies, and disposing the composition in the spacer after placing the spacer between the vertebral bodies. The teachings of Hunt ‘949 remedy those deficiencies.
Hunt ‘949 discloses methods for treating a degenerative intervertebral disc disorder comprising implanting a disc stabilization device into a subject and administering at least one therapeutic agent that promotes healing of the disc to the subject (see Abstract), wherein degenerative changes in the spine often cause the loss of normal structure and/or function, and the intervertebral disc is a structure prone to the degenerative changes associated with wear and tear, aging, and misuse (see ¶[0003]), wherein, when degeneration reaches an advanced stage, it is often necessary to remove the natural intervertebral disc and to replace it and, if the entire disc is removed, spinal column instability may warrant fusion which involves placing bone graft from the patient's pelvic bone and inserting metal rods or cages to stabilize the spine, allowing for the relief of pain by eliminating movement at the motion segment, it often decreases the patient's functional range of motion and may increase stress to the adjacent discs and facet joints (see ¶[0004]), wherein alternatively, the disc may be completely replaced with an artificial disc, which is mounted between the vertebrae and which, ideally, conserves for the patient all of the
relative mobility between the vertebrae (see ¶[0005]), wherein the disc stabilization device is load-bearing (see ¶[0012]), wherein the disc stabilization device is an intradiscal stabilization device, such as an intervertebral device (see ¶[0016]), wherein an intradiscal stabilization implant or intradiscal stabilization device includes any device or implant that can be placed within the disc space, on the disc, or as a replacement to the disc, or a portion thereof, the device changing the size or shape within the disc space once implanted (see ¶[0046]), wherein the therapeutic agent is delivered using a delivery means such as direct injection or implantation with a drug delivery implant (see ¶[0025]), wherein the method further comprises administering a regenerative growth factor which restores or improves disc tissue (see ¶[0026]), wherein a device such as an interspinous spacer may be fixed between the spinous processes of two consecutive vertebrae that come into contact on movement of the spine, using appropriate fixing means, the spacer intended to establish a specified space between the vertebrae on either side of the intervertebral disc being treated, thus limiting the mechanical stresses on that disc (see ¶[0072]), wherein the therapeutic agent may be a polypeptide drug possessing a desired activity, such as platelet derived growth factor (see ¶[0158]), wherein the therapeutic agent may be administered using a sustained delivery device that is adapted to remain within the disc for a prolonged period and slowly release the therapeutic agent contained therein to the surrounding environment, allowing the therapeutic agent to remain in therapeutically effective amounts within the disc for a prolonged period (see ¶[0159]), wherein the therapeutic agent may be administered locally by direct injection into the subject with the damaged disc, and wherein the disc implant may be implanted in the subject prior to, concurrent with, or following administration of the therapeutic agent with a drug carrier or drug delivery system that is optimized for treatment of a degenerative spinal disorder (see ¶[0174]).
Application of the Cited Art to the Claims
It would have been prima facie obvious before the filing date of the claimed invention to
treat structures of the vertebral column, including vertebral bodies, by a method comprising providing a composition comprising a PDGF solution and a biocompatible matrix and applying the composition to at least one vertebral body, according to the teachings of Hart ‘515, wherein the method further comprises implanting a disc stabilization device into a subject comprising a therapeutic agent that promotes healing of the disc, wherein the disc stabilization device is an intradiscal stabilization device, such as an intervertebral spacer, wherein the therapeutic agent is delivered by direct injection or implantation with a drug delivery implant, wherein the therapeutic agent comprises a regenerative growth factor that restores or improves disc tissue, wherein the interspinous spacer is fixed between the spinous processes of two consecutive vertebrae that come into contact on movement of the spine, using appropriate fixing means, the spacer intended to establish a specified space between the vertebrae on either side of the intervertebral disc being treated, thus limiting the mechanical stresses on that disc, wherein the therapeutic agent may be a polypeptide drug possessing a desired activity, such as platelet derived growth factor, wherein the therapeutic agent is administered using a sustained delivery device that is adapted to remain within the disc for a prolonged period and slowly release the therapeutic agent contained therein to the surrounding environment, allowing the therapeutic agent to remain in therapeutically effective amounts within the disc for a prolonged period, and wherein the disc implant may be implanted in the subject prior to, concurrent with, or following administration of the therapeutic agent with a drug carrier or drug delivery system that is optimized for treatment of a degenerative spinal disorder, as taught by Hart ‘949. 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 Hart ‘959 to the effect that implanting an intervertebral spacer allows for limiting the mechanical stresses on an injured or degenerated disc, and loading the device with the PDGF composition in a collagen matrix with β-TCP makes it possible for the therapeutic agent to remain in therapeutically effective amounts within the disc spacer for a prolonged period.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by claims 35 – 37 would have been obvious within the meaning of 35 USC § 103.
NO CLAIM IS ALLOWED.
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 am - 5:30 pm.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, David J 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.
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/DANIEL F COUGHLIN/
Examiner, Art Unit 1619
/DAVID J BLANCHARD/ Supervisory Patent Examiner, Art Unit 1619
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