DETAILED ACTION
Status of Claims
Claims 1-24 are currently pending and are the subject of this Office Action. This is the first Office Action on the merits of the claims. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Office Action: Non-Final
Claim Rejections – 35 U.S.C. § 112 - Indefiniteness
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 10-11 are rejected under 35 U.S.C. § 112 (b) or 35 U.S.C. § 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or, for pre-AIA , that applicant regards as the invention.
Claims 10-11 contains the trademark/trade name “bioglass.” Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. § 112, second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe “bioactive glass” and, accordingly, the identification/description is indefinite.
Further clarification is required.
Claim Rejections – 35 U.S.C. § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. § 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-4, 6, 10 and 13-21 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by YANG I (US 2017/0080125 A1, Publ. Mar. 23, 2017; hereinafter, “Yang I”).
Yang I is directed to:
METHODS OF PROMOTING BONE GROWTH AND HEALING
ABSTRACT
In one aspect, methods of promoting bone growth are described herein. In some embodiments, a method described herein comprises disposing a graft or scaffold in a bone growth site. The graft or scaffold comprises (a) a polymer network formed from the reaction product of (i) citric acid, a citrate or an ester of citric acid with (ii) a polyol. The graft or scaffold further comprises (b) a particulate inorganic material dispersed in the polymer network.
Yang I, title & abstract. In this regard, Yang I teaches “Polymer Networks” obtained from “Equimolar amounts of citric acid and 1,8-octanediol”:
Example 1
Polymer Networks
[0111] Polymer networks suitable for use in some embodiments of methods of promoting bone growth or repair described herein were prepared as follows. Specifically, poly(1,8-octanediol-co-citric acid) (POC) synthesis was carried out according to the following method.
[0112] Equimolar amounts of citric acid and 1,8-octanediol were added to a 250 mL three-neck round-bottom flask fitted with an inlet and outlet adapter. The mixture was melted under a flow of nitrogen gas by stirring at 160-165° C. in a silicon oil bath. The temperature was then lowered to 140° C. The mixture was stirred for an hour at 140° C. to create a “pre-polymer” solution. The pre-polymer solution was post-polymerized at 37° C., 60° C., 80° C., or 120° C. under vacuum (2 Pa) or at ambient pressure for times ranging from 1 day to 2 weeks to create POC with various degrees of cross-linking.
[0113] In addition to POC, several other citric acid based elastomers were synthesized as described above using other diols. The resulting copolymers were poly(1,6-hexanediol-co-citric acid) (PHC), poly(1,10-decanediol-co-citric acid) (PDC), and poly(1,12-dodecanediol-co-citric acid) (PDDC).
(Yang I, par. [0111]-[0113], Ex. 1) that is formed into a scaffold with “Hydroxyapatite (HA)”:
Example 3
Scaffolds
[0118] Scaffolds suitable for use in some embodiments of methods of promoting bone growth or repair described herein were prepared as follows.
[0119] First, sodium chloride crystals were ground and separated by sieve into differing sizes ranging from 50 μm to 1000 μm. Hydroxyapatite (HA) and a pre-polymer, such as poly(1,8-octanediol) (POC) consistent with Example 1, crosslinkable urethane doped elastomer (CUPE) consistent with Example 2, or other citrate-based polymers were dissolved in 1,4-dioxane solvent at HA ratios (relative to the combined weight of HA and polymer) of 0 to 65 wt.-% under continuous stirring in a TEFLON® (commercially available from DuPont) dish. Next, salt was added to the above solutions with a salt weight ratio (based on the total weight of salt, polymer, and HA) from 0 to 90 wt.-%. The resulting slurry was stirred until nearly all of the solvent evaporated. The mixture was then transferred to molds.
[0120] Specifically, scaffolds were made using a cylindrical TEFLON® mold with a 4 mm inner diameter. After molding and ejection from the mold, all scaffolds were crosslinked at 80-100° C. for 3 days. After crosslinking, salt was leached out by immersing the scaffolds in distilled water. The salt leaching process was carried out for a time period up to 3 weeks, with water changes made at least every other day. Frequent water changes, applying vacuum and heating, or using a swelling solvent like ethanol could be used to reduce the time needed to remove all of the salt from the scaffolds. After salt leaching, scaffold samples were freeze-dried and sterilized before their use in animal studies.
(Yang I, par. [0118]-[0120], Ex. 3).
Regarding independent claim 1 and the requirements:
1. A composition for use as a bone grating material, comprising:
a. a citrate component,
b. a polyol, and
c. particulate inorganic material.
Yang I clearly teaches “Polymer Networks” obtained from “Equimolar amounts of citric acid and 1,8-octanediol” (Yang I, par. [0111]-[0113], Ex. 1) that is formed into “Scaffolds” with “Hydroxyapatite (HA)” (Yang I, par. [0118]-[0120], Ex. 3), WHEREBY it is noted:
“citric acid” (Yang I, par. [0112], Ex. 1) in “poly(1,8-octanediol-co-citric acid) (POC)” (Yang I, par. [0111], Ex. 1) reads on a “citrate component” of claims 1-2, as well as “citric acid” of claim 2:
2. The composition of claim 1, wherein the citrate component comprises one or more of citric acid, citrate, or an ester of citric acid.
“1,8-octanediol” (Yang I, par. [0112], Ex. 1) in “poly(1,8-octanediol-co-citric acid) (POC)” (Yang I, par. [0111], Ex. 1) reads on a “polyol” of claims 1 and 3, as well as “diol” of claim 3, and “octanediol” of claim 4:
3. The composition of claim 1, wherein the polyol comprises a diol.
4. The composition of claim 3, wherein the diol comprises one or more of butanediol, hexanediol, octanediol, or polyethylene glycol.
“Hydroxyapatite (HA)” (Yang I, par. [0119], Ex. 3) in the “Scaffolds” (Yang I, par. [0118]-[0120], Ex. 3) reads on a “particulate inorganic material” of claim 1, as well as “hydroxyapatite” of claim 10:
10. The composition of claim 1, wherein the particulate inorganic material comprises one or more of hydroxyapatite, tricalcium phosphate, biphasic calcium phosphate, calcium carbonate, carbonated apatite, and bioglass.
Thus, Yang I anticipates claims 1-4 and 10.
Regarding claim 6 and the requirements:
6. The composition of claim 1, wherein the citrate and polyol are reacted at a 1.0:1.0 to 1.0:1.5 molar ratio, respectively, to form a telechelomer.
Yang I teaches “poly(1,8-octanediol-co-citric acid) (POC) synthesis” (Yang I, par. [0111], Ex. 1) from “Equimolar amounts of citric acid and 1,8-octanediol” (Yang I, par. [0111], Ex. 1), which reads on a “telechelomer” of claim 6. Regarding the requirements of claim 6 for “wherein the citrate and polyol are reacted at a 1.0:1.0 to 1.0:1.5 molar ratio, respectively,”it is noted that MPEP § 2131.03 states “[W]hen, as by a recitation of ranges or otherwise, a claim covers several compositions, the claim is 'anticipated' if one of them is in the prior art.” Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (citing In re Petering, 301 F.2d 676, 682, 133 USPQ 275, 280 (CCPA 1962)).
Thus, Yang I anticipates claim 6.
Regarding claims 13-14 and the requirements:
13. The composition of claim 1, wherein the particulate inorganic material comprises a bioceramic that is micro-sized or nano-sized.
14. The composition of claim 1, wherein the particulate inorganic material comprises a bioceramic that is rod-shaped.
Yang I teaches a “particulate material” such as “hydroxyapatite” (Yang I, par. [0094]) having “an average particle size in at least one dimension of less than about 1000 μm, […], or less than about 10 μm” or “at least one dimension of less than about 1 μm, less than about 500 nm, less than about 300 nm, less than about 100 nm, less than about 50 nm, or less than about 30 nm” including “needle-like particles”
[0095] In addition, a particulate material described herein can have any particle size and/or particle shape not inconsistent with the objectives of the present disclosure. In some embodiments, for instance, a particulate material has an average particle size in at least one dimension of less than about 1000 μm, less than about 800 μm, less than about 500 μm, less than about 300 μm, less than about 100 μm, less than about 50 μm, less than about 30 μm, or less than about 10 μm. In some cases, a particulate material has an average particle size in at least one dimension of less than about 1 μm, less than about 500 nm, less than about 300 nm, less than about 100 nm, less than about 50 nm, or less than about 30 nm. In some instances, a particulate material has an average particle size recited herein in two dimensions or three dimensions. Moreover, a particulate material can be formed of substantially spherical particles, plate-like particles, needle-like particles, or a combination thereof. Particulate materials having other shapes may also be used.
(Yang I, par. [0095]), which reads on a “bioceramic” of claims 13-14 (as well as par. [0039] of the instant published application, US 2024/0216574 A1) that is “micro-sized” and “nano-sized” of claim 13, and “rod-shaped” of claim 14.
Thus, Yang I anticipates claims 13-14.
Regarding claim 15 and the requirements:
15. A scaffold formed at least in part from the composition of claim 1, wherein the scaffold is a crosslinked polymer network.
“Polymer Networks” obtained from “Equimolar amounts of citric acid and 1,8-octanediol” (Yang I, par. [0111]-[0113], Ex. 1) that is formed into “Scaffolds” with “Hydroxyapatite (HA)” (Yang I, par. [0118]-[0120], Ex. 3), wherein the “citric acid and 1,8-octanediol […] create [a] POC with various degrees of cross-linking” (Yang I, par. [0112], Ex. 1), which reads on a “crosslinked polymer network” of claim 15.
Thus, Yang I anticipates claim 15.
Regarding claims 16 and 18-21, it is noted that the requirements:
16. The scaffold of claim 15, wherein the scaffold is biodegradable.
[…]
18. The scaffold of claim 15, wherein the scaffold is conformable.
20. The scaffold of claim 15, wherein the scaffold is adapted to swell in liquids by 500-1500%.
21. The scaffold of claim 15, wherein the scaffold fully degrades between 6-12 months in vivo.
are functional limitations. In this regard, it is noted that the structure, material or act in the claim that is connected to (i.e., performs) the recited function is the combination of recited elements of claims 1 and 15, which achieve the resulting biodegradation, conformation, swelling and degradation effects. Therefore, the broadest reasonable interpretation (see MPEP § 2111 with respect to broadest reasonable interpretation) of the functional language is: an intended biodegradation, conformation, swelling and degradation effect of a composition and scaffold that meets the structural requirements of claims 1 and 15. Because this functional language merely recites the intended result of the recited structural limitations, it imposes no patentable distinction on the claim (i.e., the functional language is not further limiting beyond the noted structural limitations). Therefore, one of ordinary skill in the art would understand that a composition meeting the structural requirements of claims 1 and 15 will achieve the intended result of the functional limitations and fall within the boundaries of the claims. In this regard, Yang I teaches a “citrate moiety in a citrate-containing polymer” conferring “tunable properties, in certain embodiments, can comprise or include one or more of: the antimicrobial properties of a citrate-containing polymer, the biodegradability of a citrate-containing polymer, and the water swellability of a citrate-containing polymer” (Yang I, par. [0060]), and “in some cases, the graft or scaffold can be maintained for at least 1 month, such as for at least 3 months, at least 6 months, at least 9 months, or at least 12 months” (Yang I, par. [0109]).
Thus, Yang I anticipates claims 16 and 18-21.
Regarding claim 17 and the requirements:
17. The scaffold of claim 15, wherein the scaffold is 50-90% porous.
Yang I teaches “Porous POC-M-click-HA composite matchstick-shaped scaffolds, with a size of 2x2x10 O mm, an HA content of 65 wt.-% relative to the combined weight of HA and polymer, a porosity of 65%, and pore size of 250-425 μm were fabricated according to the following method.” Yang I, par. [0136], Ex. 6. See MPEP § 2131.03 regarding prior art anticipating claimed numerical ranges.
Thus, Yang I anticipates claim 17.
Regarding claim 19, it is noted that the requirements:
19. The scaffold of claim 15, wherein the scaffold is configured and adapted to be cut in an operating room.
are recitation of intended use. In this regard, it is noted that recitations of intended use must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it reads on the claim. See MPEP § 2103 (I)(C)). Since Yang I teaches the structure for the scaffold of the instant claims, then it reasonably follows that Yang I’s scaffold would be capable of performing the intended use. Further in this regard, it is noted that Yang I teaches a “Porous POC-M-click-HA composite matchstick-shaped scaffolds, with a size of 2x2x10 O mm” (Yang I, par. [0136], Ex. 6) that reads on being “configured and adapted to be cut in an operating room” of claim 19.
Thus, Yang I anticipates claim 19.
Claim Rejections – 35 U.S.C. § 103
The following is a quotation of 35 U.S.C. § 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries 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 pre-AIA 35 U.S.C. § 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 C.F.R. § 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 1-7, 10-21 and 24 are rejected under 35 U.S.C. § 103 as being unpatentable over YANG I (US 2017/0080125 A1, Publ. Mar. 23, 2017; hereinafter, “Yang I”).
The teachings of Yang I, as set forth in the above rejection of claims 1-4, 6, 10 and 13-21 under 35 U.S.C. § 102 (a)(1) are hereby incorporated. However, to the extent that Yang I DOES NOT EXPRESSLY TEACH a specific exemplary embodiment meeting the requirements of claims 5, 7, 11-12 and 24, the requirements thereof would be obvious.
Regarding claims 5 and 7 and the requirements:
5. The composition of claim 1, wherein the polyol comprises one or more of glycerol, beta-glycerol phosphate, or xylitol.
[…]
7. The composition of claim 1, wherein the polyol comprises glycerol at 1-40 mol % of the total polyol included in the composition.
Yang I teaches a claim embodiment drawn to:
1. A method of promoting bone growth comprising:
disposing a scaffold in a bone growth site, the scaffold comprising:
(a) a polymer network formed from the reaction product of (i) citric acid, a citrate, or an ester of citric acid with (ii) a polyol; and
(b) a particulate inorganic material dispersed in the polymer network.
(Yang I, claim 1), as well as a claim embodiment drawn to “a polymer is formed from one or more such monomers comprising a polycarboxylic acid or polycarboxylic acid equivalent; one or more monomers comprising a polyol; and one or more monomers comprising one or more clickable moieties, such as one or more alkyne moieties and/or one or more azide moieties,” wherein “the polyol can comprise a diol such as a diol provided above or a triol such as glycerol” (Yang I, par. [0090]), which reasonably encompasses embodiments containing glycerol in a combination with other polyols, and relates to “glycerol” of claims 5 and 7. Yang I also teaches a proportion of the “citrate moiety,” i.e., component (a)(i) of Yang I’s claim embodiment, “at least about 30 mole percent, at least about 40 mole percent, or at least about 50 mole percent citrate moiety, based on the total number of moles of the comonomers of the polymer” (Yang I, par. [0060]) by which “, one or more properties of a polymer may be tuned based on the amount of the citrate moiety as well as on one or more other features of the chemical structure of the polymer”:
[0061] Additionally, in some cases, one or more properties of a polymer may be tuned based on the amount of the citrate moiety as well as on one or more other features of the chemical structure of the polymer. Moreover, one or more properties may be tunable independently of one or more other properties. For example, in some cases, the water uptake and/or degradation rate of a polymer described herein can be tuned for a desired application. Such tunability can provide advantages to a composition of a graft or scaffold utilized in a method described herein. […].
(Yang I, par. [0061]). In this regard, it is noted that a reference is analyzed using its broadest teachings. MPEP § 2123 [R-5] states: “[W]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious.” KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007)(quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to rearrange Yang I’s claim embodiment with “(a) a polymer network formed from the reaction product of (i) citric acid, a citrate, or an ester of citric acid with (ii) a polyol” (Yang I, claim 1) so that the “(ii) polyol” component contains glycerol in a combination with other polyols (Yang I, par. [0090]); wherein component (i), the citrate moiety is present “at least about 30 mole percent, […] of the comonomers of the polymer” (Yang I, par. [0060]), and component (ii) makes up the remainder of 30 mole percent or less. In this regard, it is noted that MPEP § 2144.05 (I), states, “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); In re Woodruff, 919 F.2d, 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).” Further in this regard, “[w]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); and also MPEP § 2144.05(II)(A). In the instant case, “the amount of the citrate moiety as well as on one or more other features of the chemical structure of the polymer” is clearly a result-effective variable, which Yang I discloses, “one or more properties may be tunable independently of one or more other properties,” e.g., “in some cases, the water uptake and/or degradation rate of a polymer described herein can be tuned for a desired application” which “tunability can provide advantages to a composition of a graft or scaffold utilized in a method described herein.” Yang I, par. [0061]. Therefore, it would have been customary for an artisan of ordinary skill to select an appropriate mol % glycerol of the total polyol content, e.g., “1-40 mol % of the total polyol” per the requirements of claim claim 7, in optimizing the polymer for water uptake and/or degradation rate.
Thus, the prior art renders claims 5 and 7 obvious.
Thus, Yang I renders claims 5 and 7 obvious.
Regarding claim 11 and the requirements:
11. The composition of claim 1, wherein the particulate inorganic material is coated with bioglass.
Yang I teaches that “the particulate material comprises one or more of hydroxyapatite, tricalcium phosphate (including α- and β-tricalcium phosphate), biphasic calcium phosphate, bioglass, ceramic, magnesium powder, magnesium alloy, and decellularized bone tissue particles”
[0094] As described herein, grafts or scaffolds can further comprise a particulate material dispersed in the polymer network of the graft or scaffold. Any particulate material not inconsistent with the objectives of the present disclosure may be used. In some cases, the particulate material comprises one or more of hydroxyapatite, tricalcium phosphate (including α- and β-tricalcium phosphate), biphasic calcium phosphate, bioglass, ceramic, magnesium powder, magnesium alloy, and decellularized bone tissue particles. Other particulate materials may also be used.
Yang I, par. [0094]. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to rearrange the disclosed above cited components of Yang I by mixing two inorganic particulate materials together with bioglass in order to obtain a “particulate inorganic material [that] is coated with bioglass” of claim 11. See MPEP § 2123 [R-5] regarding the obviousness of rearranging a reference according to the teachings of that same reference.
Thus, Yang I renders claim 11 obvious.
Regarding claim 12 and the requirements:
12. The composition of claim 1, wherein the particulate inorganic material comprises a bioceramic present in an amount between 10 and 50 wt.- % of the composition.
Yang I teaches “Hydroxyapatite (HA) and a pre-polymer, such as poly(1,8-octanediol) (POC) consistent with Example 1, […], or other citrate-based polymers were dissolved in 1,4-dioxane solvent at HA ratios (relative to the combined weight of HA and polymer) of 0 to 65 wt.-% under continuous stirring in a TEFLON® (commercially available from DuPont) dish” (Yang I, par. [0119], Ex. 3). See MPEP § 2144.05 (I) regarding the obviousness of prior art overlapping claimed numerical ranges.
Thus, Yang I renders claim 12 obvious.
Regarding claim 24 and the requirements:
24. The scaffold of claim 15, further comprising a peptide conjugated to the scaffold.
Yang I teaches “in some embodiments, a polymer described herein can be functionalized with a bioactive species,” e.g., “a polymer described herein is formed from one or more monomers comprising a peptide, polypeptide”:
[0084] Additionally, in some embodiments, a polymer described herein can be functionalized with a bioactive species. In some cases, the polymer is formed from an additional monomer comprising the bioactive species. Moreover, such an additional monomer can comprise one or more alkyne and/or azide moieties. For example, in some instances, a polymer described herein is formed from one or more monomers comprising a peptide, polypeptide, nucleic acid, or polysaccharide, wherein the peptide, polypeptide, nucleic acid, or polysaccharide is functionalized with one or more alkyne and/or azide moieties. In some cases, the bioactive species of a polymer described herein is a growth factor or signaling molecule. Further, a peptide can comprise a dipeptide, tripeptide, tetrapeptide, or a longer peptide. As described further hereinbelow, forming a polymer from such a monomer, in some embodiments, can provide additional biological functionality to a composition described herein.
(Yang I, par. [0084]), which is a “peptide conjugated to the scaffold” of claim 24.
Claim 8 is rejected under 35 U.S.C. § 103 as being unpatentable over YANG I (US 2017/0080125 A1, Publ. Mar. 23, 2017; hereinafter, “Yang I”), as applied to claims 1-7, 10-21 and 24, above, and further in view of He (He, Y., et al., Development of osteopromotive poly (octamethylene citrate glycerophosphate) for enhanced bone regeneration, Acta Biomater., 93 (2019) pp. 180-191; hereinafter, “He”).
The teachings of Yang I, as set forth above, are hereby incorporated. However, BEHNAM DOES NOT EXPRESSLY TEACH the requirements of claim 8 for:
8. The composition of claim 1, wherein the polyol comprises beta-glycerol phosphate at 1-40 mol %, of the total polyol included in the composition.
since the choice of the particular polyol is well within the purview of the ordinarily skilled artisan.
He, for instance is directed to:
Development of osteopromotive poly (octamethylene citrate glycerophosphate) for enhanced bone regeneration
ABSTRACT
The design and development of bioactive materials that are inherently conducive for osteointegration and bone regeneration with tunable mechanical properties and degradation remains a challenge. Herein, we report the development of a new class of citrate-based materials with glycerophosphate salts, β-glycerophosphate disodium (β-GP-Na) and glycerophosphate calcium (GP-Ca), incorporated through a simple and convenient one-pot condensation reaction, which might address the above challenge in the search of suitable orthopedic biomaterials. Tensile strength of the resultant poly (octamethylene citrate glycerophosphate), POC-βGP-Na and POC-GP-Ca, was as high as 28.2 ± 2.44 MPa and 22.76 ± 1.06 MPa, respectively. The initial modulus ranged from 5.28 ± 0.56 MPa to 256.44 ± 22.88 MPa. The mechanical properties and degradation rate of POC-GP could be controlled by varying the type of salts, and the feeding ratio of salts introduced. Particularly, POC-GP-Ca demonstrated better cytocompatibility and the corresponding composite POC-GP-Ca/hydroxyapatite (HA) also elicited improved osteogenic differentiation of human mesenchymal stem cells (hMSCs) in vitro, as compared to POC-βGP-Na/HA and POC/HA. The superior in-vivo performance of POC-GP-Ca/HA microparticle scaffolds in promoting bone regeneration over POC-βGP-Na/HA and POC/HA was further confirmed in a rabbit femoral condyle defect model. Taken together, the tunability of mechanical properties and degradation rates, together with the osteopromotive nature of POC-GP polymers make these materials, especially POC-GP-Ca well suited for bone tissue engineering applications.
(He, title & abstract), wherein “POC-βGP-Na” is noted as encompassed by “beta-glycerol phosphate” of claim 8.
In light of these teachings, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to formulate Yang I’s “poly(1,8-octanediol-co-citric acid) (POC) synthesis” (Yang I, par. [0111], Ex. 1), and to have substituted 1,8-octanediol for “β-glycerophosphate disodium (β-GP-Na)” per He (He, abstract). One would have been motivated to do so with a reasonable expectation of success in order to obtain the advantage of “suitable orthopedic biomaterials” for imparting “[t]ensile strength” (He, abstract). Since, it would have been customary for an artisan of ordinary skill to select an appropriate mol % glycerol of the total polyol content, e.g., “1-40 mol % of the total polyol” per the requirements of claim claim 7, in optimizing the polymer for water uptake and/or degradation rate, it would likewise be customary to optimize the amount of “β-glycerophosphate disodium (β-GP-Na)” as part of the polyol content of Yang I’s polymer,
Thus, the prior art renders claim 8 obvious.
Claim 9 is rejected under 35 U.S.C. § 103 as being unpatentable over YANG I (US 2017/0080125 A1, Publ. Mar. 23, 2017; hereinafter, “Yang I”), as applied to claims 1-7, 10-21 and 24, above, and further in view of YANG II (CA 3 172 926 A1, Publ. Oct. 14, 2021; hereinafter, “Yang II”).
The teachings of Yang I, as set forth above, are hereby incorporated. However, Yang I DOES NOT EXPRESSLY TEACH the requirements of claim 9 for:
9. The composition of claim 1, wherein the polyol comprises xylitol at 1-40 mol % of the total polyol included in the composition.
since the choice of the particular polyol is well within the purview of the ordinarily skilled artisan.
Yang II, for instance is directed to:
XYLITOL-DOPED CITRATE COMPOSITIONS AND USES THEREOF
Abstract
The present disclosure provides compositions which may be used as tissue engineering materials, and more particularly xylitol-doped citrate polymer compositions which may be useful as bone grafts.
(Yang II, title & abstract) for “improved mechanical properties, degradation rate and bioactivity while still maintaining biodegradability” (Yang II, p. 2, ln. 24-27). In this regard, teaches that “Xylitol doped polymers may be synthesized with to varying xylitol contents from greater than 0 to less than 100% diol substitution” for “fabricating xylitol doped POC materials (e.g., polymers, films, scaffolds, and compositions, etc.)” such as “citric acid and octanediol/xlitol”:
Examples of methods disclosed herein involve fabricating xylitol doped POC materials (e.g., polymers, films, scaffolds, and compositions, etc.). Polymers other than POC can be used, such a biodegradable photoluminescent polymers (BPLPs), injectable citrate-based mussel inspired bioadhesives (iCMBA), etc. Xylitol can be incorporated into 30 the polymer via esterification. In one representative example, citric acid and octanediol/xlitol with a 1:1 mole ratio can be melted at 160 C under stirring for ten minutes. The reaction temperature can then he reduced to 140 C, wherein the reaction proceeds until the pre-polymer can no longer be stirred due to viscosity, at which point the reaction may be quenched with dioxane. Following polymerization, the pre-polymer can be purified by precipitation in deionized water, lyophilized, and dissolved in organic solvent to form pre-polymer solutions.
Xylitol doped citrate-based polyesters may be synthesized via the above general procedure using a variety of diols. Suitable diols can be small molecule diols such as 1,2-ethylene glycol, 1,3-propanediol, 1,4-butanediol, 1,5-pentanediol, 1,6-hexanediol, 1,8-octanediol, 1,10-decanediol, and 1,12-dodecanediol or macrodiols such as poly(ethylene glycol) (PEG) or combinations thereof. Xylitol doped polymers may be synthesized with citrate:diol+xylitol ratios of 1.5:1 to 1:1.5. Xylitol doped polymers may be synthesized with to varying xylitol contents from greater than 0 to less than 100% diol substitution.
Yang II, p. 36, ln. 26 to p. 37, ln. 10.
In light of these teachings, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to formulate Yang I’s “poly(1,8-octanediol-co-citric acid) (POC) synthesis” (Yang I, par. [0111], Ex. 1) as “xylitol doped POC materials (e.g., polymers, films, scaffolds, and compositions, etc.)” such as “citric acid and octanediol/xlitol” (Yang II, p. 36, ln. 26 to p. 37, ln. 10).
One would have been motivated to do so with a reasonable expectation of success in order to obtain the advantage of “improved mechanical properties, degradation rate and bioactivity while still maintaining biodegradability” (Yang II, p. 2, ln. 24-27), wherein “Xylitol doped polymers may be synthesized with to varying xylitol contents from greater than 0 to less than 100% diol substitution” (Yang II, p. 36, ln. 26 to p. 37, ln. 10). See MPEP § 2144.05 (I) regarding the obviousness of prior art overlapping claimed numerical ranges.
Thus, the prior art renders claim 9 obvious.
Claims 22-23 are rejected under 35 U.S.C. § 103 as being unpatentable over YANG I (US 2017/0080125 A1, Publ. Mar. 23, 2017; hereinafter, “Yang I”), as applied to claims 1-7, 10-21 and 24, above, and further in view of YANG III (US 2020/0093770 A1, Publ. Mar. 26, 2020; hereinafter, “Yang III”).
The teachings of Yang I, as set forth above, are hereby incorporated. However, Yang I DOES NOT EXPRESSLY TEACH the requirements of claims 22-23 for a “microparticulate scaffold” or “paste”:
22. The scaffold of claim 15, wherein the scaffold is microparticulate.
23. The scaffold of claim 22, wherein the microparticulate scaffold is paste.
since the choice of the particular compositional form is well within the purview of the ordinarily skilled artisan
Yang III, for instance is drawn to:
COMPOSITIONS AND METHODS FOR PROMOTING BONE REGENERATION
ABSTRACT
This invention relates to compositions and methods for promoting and/or accelerating bone regeneration, repair, and/or healing and, in particular, to compositions and methods of promoting bone regeneration, growth, repair, and/or healing using graft or scaffold materials. In exemplary embodiments, the disclosed compositions may be used to promote and/or accelerate bone regeneration by delivering a composition to a bone site, the composition comprising (a) a citrate component, (b) a phosphate component, and, optionally, (c) a particulate inorganic material. The citrate component and/or phosphate component is advantageously released from the composition at the bone site. The released citrate component may function to increase alkaline phosphatase activity and/or expression at the bone site, and the increased alkaline phosphatase activity and/or expression may release the phosphate component. The composition may be delivered in various forms, e.g., as a biodegradable scaffold.
(Yang III, title & abstract). In this regard, teaches suitable compositional forms including a “biodegradable scaffold [that] is microparticulate” and a “paste”:
[0008] In some embodiments, the biodegradable scaffold is microparticulate. Additionally, the microparticulate scaffold, in some embodiments, is a paste. In some cases, the biodegradable scaffold is a polymer network. In some cases, the scaffold comprises at least 20 weight percent, at least 30 weight percent, or at least 40 weight percent particulate inorganic material, based on the total weight of the scaffold.
(Yang III, par. [0008]), which is “microparticulate scaffold” of claim 24, and “paste” of claim 23.
In light of these teachings, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to formulate Yang I’s “poly(1,8-octanediol-co-citric acid) (POC) synthesis” (Yang I, par. [0111], Ex. 1) as a “biodegradable scaffold [that] is microparticulate” and a “paste” per Yang III (Yang III, par. [0008]). One would have been motivated to do so with a reasonable expectation of success in order to obtain the advantage of suitable compositional forms such as a “biodegradable scaffold [that] is microparticulate” and a “paste” (Yang III, par. [0008]) for “a composition to a bone site, the composition comprising (a) a citrate component, (b) a phosphate component, and, optionally, (c) a particulate inorganic material” (Yang III, abstract).
Thus, the prior art renders claims 22-23 obvious.
Claim Rejections - Nonstatutory Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 1-4, 10, 12-21 and 24 are provisionally rejected on the ground of nonstatutory double patenting over claims 1-9, 11, 14-16, 20-21 and 23-26 of copending Application No. 18/397,950 (‘950 Application). This is a provisional double patenting rejection since the conflicting claims have not in fact been patented.
Although the conflicting claims are not identical, they are not patentably distinct because the instant claims as well as the copending claims are drawn to a contrast/composition featuring a citrate component, a polyol component and a particulate inorganic component.
Claim 1 is anticipated by claim 1 of the ‘950 Application.
Claim 2 is anticipated by claim 2 of the ‘950 Application.
Claim 3 is anticipated by claim 1 of the ‘950 Application.
Claim 4 is anticipated by claim 3 of the ‘950 Application.
Claim 5 is anticipated by claim 4 of the ‘950 Application.
Claim 6 is anticipated by claim 7 of the ‘950 Application.
Claim 10 is anticipated by claim 5 of the ‘950 Application.
Claim 12 is anticipated by claim 14 of the ‘950 Application.
Claim 13 is anticipated by claim 15 of the ‘950 Application.
Claim 14 is anticipated by claim 6 of the ‘950 Application.
Claim 15 is anticipated by claim 8 of the ‘950 Application.
Claim 16 is anticipated by claim 11 of the ‘950 Application.
Claim 17 is anticipated by claim 9 of the ‘950 Application.
Claim 18 is anticipated by claim 23 of the ‘950 Application.
Claim 19 is anticipated by claim 24 of the ‘950 Application.
Claim 20 is anticipated by claim 25 of the ‘950 Application.
Claim 21 is anticipated by claim 26 of the ‘950 Application.
Claim 24 is anticipated by claims 16 and 20-21 of the ‘950 Application.
Claims 1-6, 10, 12-17 and 24 are provisionally rejected on the ground of nonstatutory double patenting over claims 1-5, 14-21 and 23-25 of copending Application No. 18/736,005 (‘005 Application). This is a provisional double patenting rejection since the conflicting claims have not in fact been patented.
Although the conflicting claims are not identical, they are not patentably distinct because the instant claims as well as the copending claims are drawn to a contrast/composition featuring a citrate component, a polyol component and a particulate inorganic component.
Claim 1 is anticipated by claims 1 and 17 of the ‘005 Application.
Claim 2 is anticipated by claim 2 of the ‘005 Application.
Claim 3 is anticipated by claim 3 of the ‘005 Application.
Claim 4 is anticipated by claim 4 of the ‘005 Application.
Claim 5 is anticipated by claim 5 of the ‘005 Application.
Claim 6 is anticipated by claim 23 of the ‘005 Application.
Claim 10 is anticipated by claim 18 of the ‘005 Application.
Claim 12 is anticipated by claim 19 of the ‘005 Application.
Claim 13 is anticipated by claim 20 of the ‘005 Application.
Claim 14 is anticipated by claim 21 of the ‘005 Application.
Claim 15 is anticipated by claim 23 of the ‘005 Application.
Claim 16 is anticipated by claim 24 of the ‘005 Application.
Claim 17 is anticipated by claim 25 of the ‘005 Application.
Claim 24 is anticipated by claim 14 and 15-16 of the ‘005 Application.
Claims 1-4, 10 and 12-14 are provisionally rejected on the ground of nonstatutory double patenting over claims 1-4 and 14-18 of copending Application No. 18/891,944 (‘944 Application). This is a provisional double patenting rejection since the conflicting claims have not in fact been patented.
Although the conflicting claims are not identical, they are not patentably distinct because the instant claims as well as the copending claims are drawn to a contrast/composition featuring a citrate component, a polyol component and a particulate inorganic component.
Claim 1 is anticipated by claims 1 and 14 of the ‘944 Application.
Claim 2 is anticipated by claim 2 of the ‘944 Application.
Claim 3 is anticipated by claim 3 of the ‘944 Application.
Claim 4 is anticipated by claim 4 of the ‘944 Application.
Claim 10 is anticipated by claim 15 of the ‘944 Application.
Claim 12 is anticipated by claim 16 of the ‘944 Application.
Claim 13 is anticipated by claim 17 of the ‘944 Application.
Claim 14 is anticipated by claim 18 of the ‘944 Application.
Conclusion
Claims 1-24 are rejected. No claims are allowed.
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/DOMINIC LAZARO/Primary Examiner, Art Unit 1611