DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group 1, claims 1-18 and 22-24, in reply filed on 08/04/2026 is acknowledged. Additionally, Applicant’s election without traverse of sulfate and sulfonate as charged moieties, readable on claims 1-5, 8-18 and 22-24 and 22-24, in reply filed on 08/04/2026 is acknowledged.
Claims 6, 7, and 19-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/04/2026.
Information Disclosure Statement
The Examiner respectfully notes that the IDS filed 09/24/2024 is for application 18/894,323 and not the instant application.
Applicant cites a number of references in the specification. The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Drawings
The drawings are objected to because the “n”, “m” and “x” signifying the repeating units of the compound in Figure 1 are never defined. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Interpretation
Claim 1 is interpreted to be a composition comprising one or more of the following components: a citrate component, a polyol and a charged moiety. While the instant specification discloses “ ‘citrate-based compositions’ and ‘citric acid-based biomaterials’ are interchangeable and refer to a polymeric compound produced by reacting citric acid with a polyol monomer to generate a polymer having a backbone that comprises hydrolysable ester bond” [p. 8], claim 1 does not recite a “citrate-based composition.”
Claim Rejections - 35 USC § 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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 15 and 22 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 15 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(b) or 35 U.S.C. 112 (pre-AIA ), 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 particulate inorganic material and, accordingly, the identification/description is indefinite.
The term “adapted to” in claim 22 is a relative term which renders the claim indefinite. The term “adapted to” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The term “adapted to” suggests modification of the composition, but neither the instant claims nor the specification disclose how the composition is modified to non-covalently bind to therapeutic molecules through a non-covalent interaction. It is not clear how far from the base composition one can deviate and still meet the requirement of the claim.
Claim Rejections - 35 USC § 112 – Improper Dependent Form
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 4 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 3 recites the polyol comprises a diol. However, claim 4, which depends on claim 3, recites the diol comprises glycerol, xylitol or polyethylene glycerol. The recitation of glycerol, xylitol or polyethylene glycerol in claim 4 improperly broadens the scope of what the diol in claim 3 because they are not diols. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-5 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception (natural phenomenon) in the form of a composition comprising citric acid, a polyol and/or a charged moiety without significantly more.
The claims are evaluated below using the “Subject Matter Eligibility Test for Products and Processes” flow chart as shown in MPEP § 2106 III.
Step 1: Are the claims to a process, machine, manufacture, or composition of matter?
Yes. Claim 1 is drawn towards a composition comprising citric acid, a polyol and/or a charged moiety. The claims read on a composition of matter, which is one of the four statutory categories.
Step 2A, Prong 1: Do the claims recite an abstract idea, law or nature, or natural phenomenon?
Yes. Each component, claimed in the alternative, is a naturally occurring compound. Citric acid or sodium citrate are naturally occurring, for example in citrus fruits, and read on the citric component of claim 1, the citrate of claim 2 and the carboxylic acid of claim 5. Glycerol, which is a 3-carbon polyol naturally occurring in the human body, reads the polyol component and the glycerol of claim 4.
The MPEP states that “if the nature-based product limitation is naturally occurring, there is no need to perform the markedly different characteristics analysis because the limitation is by definition directed to a naturally occurring product and thus falls under the product of nature exception.” See MPEP 2106.04(c)(I). In the present case, instant claims 1-5 fall under the product of nature exception because they claim a product which by definition is naturally occurring.
Step 2A, Prong 2: Do the claims recite additional elements that integrate the judicial exception into a practical application?
No. Claims 1-5 recite nothing more than a naturally occurring product. Therefore, claims 1-5 are not integrated into a practical application because there are no additional elements to demonstrate the claims are patent eligible.
Step 2B: Do the claims recite additional elements that amount to significantly more than the judicial exception?
No. Claims 1-5 recite nothing more than a naturally occurring product.
As claims 1-5 recites a judicial exception that is not integrated into a practical application and recites no elements that amount to significantly more than the judicial exception, the claims are drawn to ineligible subject matter under 35 U.S.C. 101.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
1) Claim(s) 1-4, 8, 11 and 22-23 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sharma et al. (Journal Of Biomedical Materials Research A, 2012, v. 100A, issue 3, p. 561-563).
Sharma discloses “Carboxylic acid groups on poly(1,8-octanediol-co-citrate) films (POCfs) were modified with heparan sulfate creating a heparan binding POCf (HBPOCf). Release of proangiogenic growth factors vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), and insulin-like growth factor 1 (IGF-1) from HBPOCfs demonstrated an approximate threefold increase over controls during a 30-day time course in vitro” [abstract].
The prior art anticipates instant claims 1-4 and 22-23 because it discloses a composition comprising citrate, a polyol (octanediol) and a charged moiety (sulfate). Wherein a peptide (insulin like growth factor 1) is conjugated to the surface of the composition. Wherein the composition is capable of non-covalently binding to a therapeutic molecule, specifically a vascular endothelial growth factor (VEGF).
Regarding claim 8, "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (See MPEP 2113.). In this case, the prior art product appears to be the same as claimed, despite not teaching the claimed conjugation step, insofar as the composition comprises a charged moiety.
2) Claim(s) 1-4, 8 and 22 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yang et al. (US 20230159698 A1, publication date 05/23/2023).
Yang relates to “compositions which may be used as tissue engineering materials, and more particularly xylitol-doped citrate polymer compositions which may be useful as bone grafts” [abstract]. According to Yang “[e]xamples of methods disclosed herein involve fabricating xylitol doped POC materials (e.g., polymers, films, scaffolds, and compositions, etc.). … In one representative example, citric acid and octanediol/xylitol with a 1:1 mole ratio can be melted at 160° C. under stirring for ten minutes” to ultimately produce a polymer [0239].
The prior art anticipates instant claims 1-4 because it discloses a composition comprising a citrate (citric acid), polyol (octanediol and xylitol) and a charged moiety (carboxylic acid of citric acid). Because the prior art contains substantially the same components as instantly claimed, it would have been expected to possess the same properties and be capable of satisfying the same applications, i.e. capable of binding a therapeutic molecule through non-covalent interaction (claim 22).
Regarding claim 8, "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (See MPEP 2113.). In this case, the prior art product appears to be the same as claimed, despite not teaching the claimed conjugation step, insofar as the composition comprises a charged moiety.
3) Claim(s) 1-4, 8, 14-17 and 22 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ameer et al. (US 2007/0224245 A1, publication date 09/27/2007).
Ameer relates to a “poly (diol citrates)-based bioceramic composite materials” [abstract]. In Example 2 of the composition, Ameer discloses POC (i.e., poly(1,8-octanediol-co-citrate) [0024]) “pre-polymer was mixed with various amounts of HA particles to obtain composites of 40, 50, 60. and 65 wt.% HA by mass” before polymerization of the POC pre-polymers [0086]. The hydroxyapatite in this example was between 45 and 75 micrometers (i.e., micro-sized; instant claim 17) [0085].
The prior art anticipates instant claims 1-4, 14, 15 and 17 because it discloses a composition comprising a citrate (citric acid), polyol (octanediol), a charged moiety (carboxylic acid of citric acid) and micro-sized inorganic particulate matter (hydroxyapatite). The prior art anticipates the instant claim 16 because it discloses the compositions comprises 40% w/w hydroxyapatite which is entirely within the instantly claimed range. Because the prior art contains substantially the same components as instantly claimed, it would have been expected to possess the same properties and be capable of satisfying the same applications, i.e. capable of binding a therapeutic molecule through non-covalent interaction (claim 22).
Regarding claim 8, "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (See MPEP 2113.). In this case, the prior art product appears to be the same as claimed, despite not teaching the claimed conjugation step, insofar as the composition comprises a charged moiety.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
1) Claim(s) 5 and 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al. (US 20230159698 A1, publication date 05/23/2023) as applied to claims 1-4 and 22 above, and further in view of Leonor et al. (J Mater Sci: Mater Med (2007) 18, p. 1923–1930) and Dinoro et al. (Biomaterials, 2019, v. 214, 119214).
Yang, which is taught above, differs from the instant claims insofar as it does not disclose instantly elected species of charged moiety, sulfate and sulfonate. As discussed above, Yang relates to “compositions which may be used as tissue engineering materials, and more particularly xylitol-doped citrate polymer compositions which may be useful as bone grafts” [abstract].
Leonor discloses “[c]ovalent coupling of sulfonic group (–SO3H) was attempted on different polymers to evaluate efficacy of this functional group in inducing nucleation of apatite in body environment and thereupon to design a simple biomimetic process for preparing bonelike apatite-polymer composites” [abstract]. According to Leonor, the “results indicate that the –SO3H groups are effective for inducing apatite nucleation, and thereby that surface sulfonation of polymers are effective pre-treatment method for preparing biomimetic apatite on their surfaces” [abstract]. According to Leonor, sulfonation is “believed promising for the production of polymer-based bioactive materials with better biocompatibility and a bone-bonding ability” [p. 1929, col. 2, final sentence]. Furthermore, Leonor discloses “sulfonation is a common procedure in material chemistry that can be defined as a substitution reaction that yields –SO3H groups on an organic compound (i.e., instant claim 8) [p. 1928, col. 1, para. 2].
Dinoro relates to sulfated polysaccharides for orthopedic tissue engineering [title]. According to Dinoro “sulfated polysaccharides are widely recognized for their ability to bind to important cell receptors to facilitate cell adhesion, proliferation and differentiation […] They can also bind to a number of important growth factors such as fibroblast, vascular endothelial and bone morphogenetic protein (BMP) growth factors for controlled growth factor release; and they can improve growth factor bioavailability by protecting them against proteinase degradation” (i.e., instant claim [p. 2, sentences spanning col. 1 and 2]. Furthermore “the bioactivity of sulfated polysaccharides depends on factors such as degree of sulfation and sulfation pattern […]. For instance, hyaluronic acid (HA)/collagen type I matrices were shown to inhibit osteoclast differentiation and resorption, largely dependent on degree of sulfation of HA [39]. To this end, highly sulfated HA was capable of improving bone regeneration in in vitro and in vivo models” [p. 2, col. 2, para. 2]. Specifically with respect to chemically sulfated polysaccharides, Dinoro discloses “[m]odifying or combining these polysaccharides with sulfate groups could exploit their native chondrogenic or osteoblastic potential whilst prolonging growth factor delivery to promote proliferation and differentiation of tissue specific stem cells, as well as circumventing shortcomings such as hypertrophy or rapid enzymatic scaffold degradation” [p. 7, col. 2, end of second para.]. Finally, Dinoro discloses that “[m]any areas within the vibrant field of tissue engineering could readily benefit from the utilization of sulfated biomaterials as a vehicle for providing growth factors to the target tissues to elicit improved cellular performance both in vitro and in vivo” [p. 17, col. 2, para. 1, last sentence].
It would have been obvious to one of ordinary skill in the art, before the effective filling date of the claimed invention, to have combined the sulfonation of Leonor with the citric acid and octanediol/xylitol polymer (i.e., poly(octanediol-co-xylitol-co-citrate); POXC) for bone grafting disclosed by Yang. One would have been motivated to sulfonate the POXC of Yang to induce hydroxyapatite nucleation and provide a polymer-based bioactive material with better biocompatibility and a bone-bonding ability, as disclosed by Leonor. One would have had an expectation of success in applying the teachings of Leonor to Yang because Leonor teaches the improved characteristics are due to the added sulfonate groups (-SO3H), as opposed to the polymeric backbone. Leonor also discloses the sulfonation process is a common procedure in chemistry, e.g., by substitution. Additionally, in combining these elements one would have expected nothing more than predictable results because, when combined by known methods, each prior art element would have performed the same function as it had separately. See MPEP 2143, Exemplary Rationale A.
It also would have been obvious to one of ordinary skill in the art, before the effective filling date of the claimed invention, to have combined the sulfation of Dinoro with the citric acid and octanediol/xlitol polymer (i.e., poly(octanediol-co-xylitol-co-citrate); POXC) for bone grafting disclosed by Yang. Dinoro relates the degree of sulfation to desirable effects such as cell adhesion, proliferation and differentiation, as well as growth factor binding and release. Accordingly, a skilled artisan would have been motivated to sulfate the POXC bone grafts taught by Yang to achieve, and tune, the desirable effects associated with the degree of sulfation, as disclosed by Dinoro. One would have had an expectation of success because Dinoro discloses that many areas of tissue engineering can utilize sulfated biomaterials. Additionally, in combining these elements one would have expected nothing more than predictable results because, when combined by known methods, each prior art element would have performed the same function as it had separately. See MPEP 2143, Exemplary Rationale A.
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filling date of the claimed invention, to have formulated the composition taught by Yang comprising a citrate component, a polyol and a charged moiety (i.e., poly(octanediol-co-xylitol-co-citrate); POXC) to further comprise sulfate and sulfonate as the charged moiety (claim 5). Wherein the charged moiety is conjugated via a substitution reaction (claim 8).
2) Claim(s) 9-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al. (US 20230159698 A1, publication date 05/23/2023) in view of Leonor et al. (J Mater Sci: Mater Med (2007) 18, p. 1923–1930) and Dinoro et al. (Biomaterials, 2019, v. 214, 119214) as applied to claims 1-5, 8 and 22 above, and further in view of Dado et al. (Kirk-Othmer Encyclopedia of Chemical Technology, Sulfonation and Sulfation, 2006).
Yang, Leonor and Dinoro, which are taught above, differ from the instant claims insofar as they do not teach a charged polyol moiety.
Dado relates to sulfation reactions, disclosing “[s]ulfonation and sulfation, chemical methods for introducing the SO3 group into organic molecules, are related and usually treated jointly” [p. 1, sentence 1]. Dado discloses “[a]lkyl and alkoxyalkyl sulfates can be produced from the corresponding alcohols or alcohol alkoxylates by reaction with a wide variety of reagents” [p. 19, last para.].
Generally, it is prima facie obvious to select a known material based on its suitability for its intended use. See MPEP 2144.07. In the present case it would have been obvious to one of ordinary skill in the art, before the effective filling date of the claimed invention, to have selected sulfation of alcohol groups on the POXC of Yang because Dado discloses sulfation of alcohols is a suitable method to for sulfating a compound. Sulfating the alcohol groups of POXC would result in a sulfated xylitol, per instant claims 9-10.
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filling date of the claimed invention, to have formulated the sulfonated and sulfated POXC taught by Yang, Leonor and Dinoro, as discussed above, to comprise sulfated xylitol (charged moiety in the polyol).
3) Claim(s) 11-12 and 22-24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al. (US 20230159698 A1, publication date 05/23/2023) in view of Leonor et al. (J Mater Sci: Mater Med (2007) 18, p. 1923–1930) and Dinoro et al. (Biomaterials, 2019, v. 214, 119214) as applied to claims 1-5, 8 and 22 above, and further in view of Ameer et al. (US 2007/0224245 A1, publication date 09/27/2007) and Sun et al. (Colloids and Surfaces B: Biointerfaces, 2018, v. 171, p. 668-674), as evidenced by Bab et al. (Biopolymers, 2004 v. 66, issue 1, p. 33-48).
Yang, Leonor and Dinoro, which are taught above, differ from the instant claims insofar as they do not teach non-covalent interactions with therapeutic molecules and surface conjugations with peptides.
Ameer “is directed to a novel poly-(diol citrates)-based bioceramic composite materials created using completely biodegradable and a bioceramic material polymers” [abstract], specifically poly(1,8-octanediol-co-citrate) [0024]. Ameer discloses it is “contemplated that the devices may be used as drug delivery system. Either the polymer, the bioceramic, or both may include a biologically-active agent” which his capable of being released from the solid implant matrix [0054]. Specifically, “[w]here the composites are used in facilitating bone repair, the composites may advantageously be impregnated with an "osteogenic agent" i.e., one which promotes, induces, stimulates, generates, or otherwise effects the production of bone or the repair of bone” [0055], such as BMP-2 (i.e., instant claims 22-24) and osteogenic growth peptide (OGP) (i.e., instant claim 11).
OGP is a protein binding peptide because OGP binds to OGP binding proteins (i.e., instant claim 12), evidenced by Bab at page 37, column 1.
Sun relates to sulfonated polyetheretherketone (PEEK) for osteogenic activity enhancement and discloses bone morphogenetic protein-2 (BMP-2) was immobilized onto the sulfonated PEEK (SPEEK) [title & abstract]. According to Sun “[t]he sulfonic groups produced by the sulfonation regulated the release of BMP-2 by electrostatic interactions and formed a slightly acidic environment on the SPEEK surface, which maintained the desired protein biological activity and optimized the BMP-2 osteoinductive activity” [p. 673, col. 1, second para.].
It would have been obvious to one of ordinary skill in the art, before the effective filling date of the claimed invention, to have combined the BMP-2 and OGP of Ameer with the bone graft material taught by Yang, Leonor and Dinoro. One would have been motivated to make this combination because Ameer discloses it advantageous to include osteogenic agents in a biomaterial based on a polyol and a citrate. One would have had an expectation of success because Ameer discloses poly(octanediol-co-citrate) is a suitable bioameterial to carry the osteogenic agent and Sun discloses sulfonated materials optimized the osteoinductive activity BMP-2. Additionally, in combining these elements one would have expected nothing more than predictable results because, when combined by known methods, each prior art element would have performed the same function as it had separately. See MPEP 2143, Exemplary Rationale A.
Furthermore, Ameer’s teaching of “impregnating” a composite of bioceramics and poly(diol citrates) based polymer, such as poly(octanediol-citrate), with a peptide would have resulted in a peptide conjugated to the surface, as recited at instant claim 11. Specifically, Ameer teaches combining an active agent, e.g., osteogenic growth peptide (OGP), with a composite comprising poly(octanediol-citrate) polymer, i.e., a polymer of citrate component, a polyol (octanediol) and a charged moiety (i.e., carboxylic acid group of citrates according to instant claim 5). According to Ameer, this combination is considered a drug delivery system wherein the active agent, e.g., OGP, is released from the composite into the surrounding tissue to facilitate bone repair. Because the prior art discloses substantially the same composition, i.e., a combination of a peptide and a polymer comprising a citrate component, polyol (octanediol) and a charged moiety (i.e., carboxylic acid group of citrate according to instant claim 5), for the same purpose of releasing the peptide into the surrounding tissue to facilitate bone repair, the composition taught by the prior reads on the instantly claimed peptide conjugated to the surface.
This is also supported by the notion of electrostatic interactions between BMP-2 and the negatively charged sulfonate groups on the polymers discussed in Sun. A skilled artisan would have expected similar electrostatic interactions between the positively charged OGP1 and the negatively charged moieties (i.e., sulfates, sulfonates and citrates) of Yang, Leonor, Dinoro and Ameer because of the opposing charges. Accordingly, the composite having negatively charged moieties impregnated with a positively charged peptide, taught by the prior, reads on the instantly claimed peptide conjugated to the surface.
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filling date of the claimed invention, to have formulated the sulfonated and sulfated POXC taught by Yang, Leonor and Dinoro, as discussed above, to further comprise BMP-2 and/or OGP, a protein binding peptide. Wherein the peptide is conjugated on the surface of the sulfonated and sulfated POXC. Wherein the therapeutic molecule (BMP-2) electrostatically interacts with the sulfonated groups, i.e., non-covalent binding (instant claim 22).
4) Claim(s) 11 and 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al. (US 20230159698 A1, publication date 05/23/2023) in view of Leonor et al. (J Mater Sci: Mater Med (2007) 18, p. 1923–1930) and Dinoro et al. (Biomaterials, 2019, v. 214, 119214) as applied to claims 1-5, 8 and 22 above, and further in view of Ameer et al. (US 2007/0224245 A1, publication date 09/27/2007), Hosseini et al. (Colloids and Surfaces B: Biointerfaces, 2019, v. 173, p. 662–671) and Sun et al. (Colloids and Surfaces B: Biointerfaces, 2018, v. 171, p. 668-674).
Yang, Leonor and Dinoro, which are taught above, differ from the instant claims insofar as they do not teach non-covalent interactions with therapeutic molecules and surface conjugations with peptides.
Ameer “is directed to a novel poly-(diol citrates)-based bioceramic composite materials created using completely biodegradable and a bioceramic material polymers” [abstract], specifically poly(1,8-octanediol-co-citrate) [0024]. Ameer discloses it is “contemplated that the devices may be used as drug delivery system. Either the polymer, the bioceramic, or both may include a biologically-active agent” which his capable of being released from the solid implant matrix [0054]. Specifically, “[w]here the composites are used in facilitating bone repair, the composites may advantageously be impregnated with an "osteogenic agent" i.e., one which promotes, induces, stimulates, generates, or otherwise effects the production of bone or the repair of bone” [0055]
Hosseini discloses a “natural peptide motif in the first helix of osteocalcin (OCN) is used to promote nucleation and crystallization of hydroxyapatite (HA) in hard tissue. The capability of osteocalcin mimetic peptides to induce osteogenic activity of osteoblast cells leading to in-vitro mineralization is demonstrated. […] It is confirmed that the osteocalcin-derived peptide, particularly in amidic form (OSN), is able to act as a bioactive inducer of mineralization process and hence accelerating bone tissue regeneration” (i.e., protein mimicking peptide; instant claim 13)[abstract]. Additionally, OSN has a positive surface charge [p. 664, col. 2, para. 1 (section 3.1)].
Sun relates to sulfonated polyetheretherketone (PEEK) for osteogenic activity enhancement and discloses bone morphogenetic protein-2 (BMP-2) was immobilized onto the sulfonated PEEK (SPEEK) [title & abstract]. According to Sun “[t]he sulfonic groups produced by the sulfonation regulated the release of BMP-2 by electrostatic interactions and formed a slightly acidic environment on the SPEEK surface, which maintained the desired protein biological activity and optimized the BMP-2 osteoinductive activity” [p. 673, col. 1, second para.].
It would have been obvious to one of ordinary skill in the art, before the effective filling date of the claimed invention, to have combined the osteocalcin-mimetic peptide, OSN, of Hosseini with the bone graft material taught by Yang, Leonor and Dinoro. One would have been motivated to make this combination because Ameer discloses it advantageous to include osteogenic agents in a biomaterial based on a polyol and a citrate while Hosseini discloses OSN is able to act as a bioactive inducer of mineralization process to accelerate bone tissue regeneration. One would have had an expectation of success because Ameer discloses poly(octanediol-co-citrate) is a suitable bioameterial to carry osteogenic agents. Furthermore, a skilled artisan would have understood to conjugate the osteogenic agent to the surface of the material taught by Yang, Leonor and Dinoro because the surface is what contacts the surrounding bone. Additionally, in combining these elements one would have expected nothing more than predictable results because, when combined by known methods, each prior art element would have performed the same function as it had separately. See MPEP 2143, Exemplary Rationale A.
Furthermore, Ameer’s teaching of “impregnating” a composite of bioceramics and poly(diol citrates) based polymer, such as poly(octanediol-citrate), with a peptide, would have resulted in a peptide conjugated to the surface, as recited at instant claim 11. Specifically, Ameer teaches combining an active agent with a composite comprising poly(octanediol-citrate) polymer, i.e., a polymer of citrate component, a polyol (octanediol) and a charged moiety (i.e., the carboxylic acid group of citrates according to instant claim 5). According to Ameer, this combination is considered a drug delivery system wherein the active agent is released from the composite into the surrounding tissue to facilitate bone repair. Because the prior art discloses substantially the same composition, i.e., a combination of a peptide (i.e., OSN) and a polymer comprising a citrate component, a polyol (octanediol), and a charged moiety (i.e., carboxylic acid group of citrate according to instant claim 5), for the same purpose of releasing the peptide into the surrounding tissue to facilitate bone repair, the composition taught by the prior art reads on the instantly claimed peptide conjugated to the surface.
This is also supported by the notion of electrostatic interactions between BMP-2 and the negatively charged sulfonate groups on the polymers discussed in Sun. A skilled artisan would have expected similar electrostatic interactions between the positively charged OSN and the negatively charged moieties (i.e., sulfates, sulfonates and citrates) of Yang, Leonor, Dinoro and Ameer because of the opposing charges. Accordingly, the composite having negatively charged moieties impregnated with a positively charged peptide, taught by the prior, reads on the instantly claimed peptide conjugated to the surface.
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filling date of the claimed invention, to have formulated the sulfonated and sulfated POXC taught by Yang, Leonor and Dinoro, as discussed above, to further comprise a protein mimicking peptide (i.e., OSN) conjugated on the surface.
5) Claim(s) 14-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al. (US 20230159698 A1, publication date 05/23/2023) as applied to claims 1-4 and 22 above, and further in view of Ameer et al. (US 2007/0224245 A1, publication date 09/27/2007).
Yang, which is taught above, differs from the instant claims insofar as it does not disclose particulate inorganic material. However, as discussed above, Yang relates to “compositions which may be used as tissue engineering materials, and more particularly xylitol-doped citrate polymer compositions which may be useful as bone grafts” [abstract].
Ameer “is directed to a novel poly-(diol citrates)-based bioceramic composite materials created using completely biodegradable and a bioceramic material polymers” [abstract], specifically poly(1,8-octanediol-co-citrate) [0024]. Ameer discloses biodegradable polymers may be made osteoconductive by the addition of bioceramics such as hydroxyapatite (i.e., instant claim 15; HA) [0028-0029]. Ameer also discloses “that poly (1,8-octanediol co-citrate) (POC), improves the processability and mechanical properties of bioceramic bone screws due to its biocompatibility, mechanical properties, controllable degradation rates” [0030]. Ameer demonstrate the preparation of bone screws made from “POC-HA [poly (1,8-octanediol co-citrate)-hydroxyapatite] composites having HA fraction of 40 wt. %, 50 wt. %, 60 wt. %, 65 wt. % HA” [0094], wherein the hydroxyapatite has a particle size of 45-75 microns (i.e., micro-sized; instant claim 17) [0085].
It would have been obvious to one of ordinary skill in the art, before the effective filling date of the claimed invention, to have combined the hydroxyapatite of Ameer with the composition disclosed by Yang because Ameer discloses bioceramics enhance osteointegration. One would have had an expectation of success because Ameer discloses pol(diol citrate) based polymers are suitable carries for hydroxyapatite particles for osteogenesis. Additionally, in combining these elements one would have expected nothing more than predictable results because, when combined by known methods, each prior art element would have performed the same function as it had separately. See MPEP 2143, Exemplary Rationale A.
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I). In the present case, the instantly claimed range of inorganic material from 10-60 % w/w overlaps with the range of the prior art from 40 to 65 % w/w, and so a prima facie case of obviousness exists.
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filling date of the claimed invention, to have formulated the compositions taught by Yang, as discussed above, to comprise micro-sized hydroxyapatite as an inorganic material within the instantly claimed amounts.
6) Claim(s) 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al. (US 20230159698 A1, publication date 05/23/2023) Ameer et al. (US 2007/0224245 A1, publication date 09/27/2007) as applied to claims 1-4, 14-17 and 22 above, and further in view of Groot-Barrere et al. (US 20160166610 A1, publication date 06/16/2016).
Yang and Ameer, which are taught above, differ from the instant claims insofar as they do not teach fiber or rod-shaped inorganic material. Ameer discloses biodegradable polymers may be made osteoconductive by the addition of bioceramics such as hydroxyapatite (HA) [0028-0029].
Groot-Barrere relates to osteoinductive calcium phosphate material and a treatment method to change calcium phosphate grains on the surface of the starting material into calcium phosphate needles [abstract]. According to Groot-Barrere “[t]he change in surface topography from a grain-like to a needle-like topography is associated with an increase in specific surface area and total pore area, consequently the surface protein adsorption capacity increases considerably” [0014]. Accordingly, Groot-Barrere “provides an osteoinductive calcium phosphate material [calcium phosphate needles], obtainable by a method according to the invention as described above” [0019] which are more osteoinductive relative to untreated particles [0008].
It would have been obvious to one of ordinary skill in the art, before the effective filling date of the claimed invention, to have substituted the hydroxyapatite in the compositions taught by Yang and Ameer for the needle shaped calcium phosphate disclosed by Groot-Barrere. One would have been motivated to make this substitution because Groot-Barrere discloses needle-shaped calcium phosphate particles have larger surface areas which results in increased protein adsorption capacity and therefore improved osteoinductivity compared to untreated particles. One would have had an expectation of success because Groot-Barrere specifically provides osteoinductive needle shaped calcium phosphate particles, as desired by Ameer. Additionally, in combining these elements one would have expected nothing more than predictable results because, when combined by known methods, each prior art element would have performed the same function as it had separately. See MPEP 2143, Exemplary Rationale A.
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filling date of the claimed invention, to have formulated the compositions taught by Yang and Ameer, as discussed above, to comprise rod-shaped (needle-shaped) inorganic material.
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 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
1) Claim 1-5, 8-18 and 22-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 13-24 of copending Application No. 18538772 (US20240216574A1). Although the claims at issue are not identical, they are not patentably distinct from each other because the conflicting claims and the copending claims recite a composition comprising a citrate component, a polyol, a charged moiety and an inorganic material [claim 1].
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
2) Claim 1-5, 8-18 and 22-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-29 of copending Application No. 18736005 (US20250228998A1). Although the claims at issue are not identical, they are not patentably distinct from each other because they both claim a composition comprising citrate component, a polyol and a charged moiety [claim 1].
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
3) Claim 1-5, 8-18 and 22-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-29 of copending Application No. 18397950 (US20240207485A1). Although the claims at issue are not identical, they are not patentably distinct from each other because they both claim a composition comprising citrate component, a polyol, a charged moiety and inorganic material [claim 1].
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
4) Claims 1-5, 8-18 and 22-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11684467 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the conflicting claims recite a composition comprising poly(1,8-octanediol-citrate) [claim 1]. Poly(1,8-octanediol-citrate) is comprises a citrate component, a polyol and the carboxylic acid of citrate suffices as the charged moiety.
5) Claims 1-5, 8-18 and 22-24 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-21 of copending Application No. 18538835 (US20240197966A1) in view of Ameer et al. (US 2007/0224245 A1, publication date 09/27/2007).
The conflicting claims recite a “patch system for use in musculoskeletal repair, comprising: a patch that defines a patch thickness, the patch fabricated, in whole or in part, from a composition that includes a citrate polymer and a bioceramic filler” [claim 1].
Ameer “is directed to a novel poly-(diol citrates)-based bioceramic composite materials created using completely biodegradable and a bioceramic material polymers” [abstract], specifically poly(1,8-octanediol-co-citrate) [0024].
Generally, it is prima facie obvious to select a known material based on its suitability for its intended use. See MPEP 2144.07. In the present case it would have been obvious to one of ordinary skill in the art, before the effective filling date of the claimed invention, to have selected the poly(1,8-octanediol-co-citrate) of Ameer as the citrate polymer desired by the conflicting claims because Ameer discloses it is a suitable citrate polymer. Poly(1,8-octanediol-citrate) is comprises a citrate component, a polyol and the carboxylic acid of citrate suffices as the charged moiety.
This is a provisional nonstatutory double patenting rejection.
Technological Background
The prior art made of record is considered pertinent to applicant's disclosure.
Greenberg et al., Mitogenic action of osteogenic growth peptide (OGP) Role of amino and carboxy-terminal regions and charge, 1993, Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1178, Issue 3, Pages 273-280. Greenberg is pertinent for teaching that OGP has a high positive net charge at the abstract.
Conclusion
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/C.T.W./ Examiner, Art Unit 1612
/WALTER E WEBB/ Primary Examiner, Art Unit 1612
1 Greenberg et al., Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1993, Volume 1178, Issue 3, Pages 273-280
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