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 II (claim 11-20) in the reply filed on 7/22/2026 is acknowledged. However, applicant did not reply to species election requirement set forth on pg. 5-8 of the office action of 5/26/2026. In order to provide compact prosecution, the examiner is selecting a single species from (a) hydrogel, and (b) growth factor promoting agent or macrophage depleting reagent.
The requirement is still deemed proper and is therefore made final.
Status of Application, Amendments, And/Or Claims
Claims 1-28 are pending.
Claims 1-10 and 21-28 are withdrawn for being drawn to non-elected inventions (i.e., Groups I and III). Claims 16 and 18 are withdrawn for being drawn to a non-elected species (as applicant’s did not elect any species).
Claims 11-15, 17, 19-20 are under examination.
Priority
The instant application is a CIP of US Application No. 16/945,270 filed on 7/31/2020, now US Pat. No. 12,053,191.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) filed on 6/23/2023 (2) and 10/13/2023 have been considered.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
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.
Claim 13 is 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 13 recites the limitation "the washing fluid" in lines 3-4. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 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.
Claim(s) 11-12 and 14 is/are rejected under 35 U.S.C. 102(a) (1) as being anticipated by Hill et al. (US Pub. No. 20050118230).
The instantly claimed invention is broadly drawn to a method of treating osteonecrosis comprising administering a hydrogel comprising collagen or a hydrogel forming peptide that is formed ex vivo or in situ for the treatment of osteonecrosis and that prevent or reduce leakage of an active agent, wherein the active agent is BMP-2, BMP-7, VEGF, clodronate or clodrosome.
Hill et al. teach treating or regenerating tissue that can be as a results of osteonecrosis comprising using a bioactive hydrogel matrix comprising polypeptide, such as gelatin (see abstract, paragraph [0003]). They teach that the bioactive hydrogel resulted greater than 20-fold increase in bone morphogenic protein (BMP-2) (see paragraph [0085]). They teach that the bioactive hydrogel further comprises at least one osteoinductive material, wherein the osteoinductive material comprises BMPs (that includes BMP-2, BMP-7), FGFs or vascular endothelial growth factors (VEGFs), collagen (see paragraph [0104], claim 36, 98). Therefore, the instantly claimed invention is implicitly or explicitly taught by the prior art.
Claim Rejections - 35 USC § 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 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.
Claim(s) 11-12, 14 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Hart et al. (US Pub. No. 20020004225).
The instantly claimed invention is broadly drawn to a method of treating osteonecrosis comprising administering a hydrogel comprising collagen or a hydrogel forming peptide that is formed ex vivo or in situ for the treatment of osteonecrosis and that prevent or reduce leakage of an active agent, wherein the active agent is BMP-2, BMP-7, VEGF, clodronate or clodrosome.
Hart et al. teach treating radiation induced osteonecrosis using zwegf3 which is structurally related to VEGF and PDGF [0020] in combination with pharmaceutically homolog to promote bone and connective tissue growth [0040]. They teach that the formulation can comprise additional growth factors and preservatives, solubilizers [0041]. They teach using useful matrix material for delivering such composition using collagen, hydroxyapatite. They teach that other growth factors include BMPs [0060].
Claim Rejections - 35 USC § 103
Claim(s) 11-15, 17, 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Hill et al. (US Pub. No. 20050118230) in view of Li et al. (Acta Biomaterialia, 13: 88-100, (2015)) and Lehenkari et al. (IDS, US 20130110112)
The instantly claimed invention is broadly drawn to a composition for treating bone osteonecrosis comprising: at least one of a Gelatin tyramine (GT), collagen, or a hydrogel-forming peptide that is formed ex vivo or in situ for the treatment of bone osteonecrosis and that prevent or reduce leakage of an active agent, wherein the active agent comprises at least one bone growth promoting agent (claim 11), wherein the growth facto agent is BMP-2, BMP-7 or VEGF (claim 12), wherein the composition is a biocompatible isotonic fluid and optionally comprises biocompatible detergents, biocompatible surfactants, biocompatible alcohols, antibiotics, preservatives, or combinations thereof, wherein the washing fluid cleans at least 50, 60, 70, 75, 80, 85, or 90% of the volume within the bone (claim 13). The method of claim 11, further comprising at least one of autologous bone marrow, autologous bone stem cells, bone graft material, bone void filler, cancellous bone graft, osteoconductive material, osteoproliferative material, osteoinductive material, or bone material infused collagen matrix (claim 14). The method of claim 11, wherein the GT is a Gelatin tyramine hydrogel, a gelatin-heparin tyramine (GHT) hydrogel, or both, which comprises a trace amount of hydrogen peroxide (0.1mM-1OmM), a horseradish peroxidase enzyme (0.1-10 unit/ml), wherein the bone growth promoting agent or a macrophage depletion reagent retains at least 80% bioactivity, and optionally comprising heparin at (0.5-5% w/v) that is formed ex vivo or in situ (claim 15), wherein the collagen is a collagen hydrogel (0.3- 3%, w/v) formed by gelation at 37°C without the addition of crosslinkers that is formed ex vivo or in situ (claim 17), wherein the composition is adapted to inject into a femoral head, a humeral head, a knee condyle, a proximal tibia, or an ankle talus (claim 19), and wherein the composition is adapted for injection into an osteonecrosis is Legg-Calv6-Perthes Disease, idiopathic (unknown cause), due to corticosteroid, trauma, alcohol, sickle cell disease, or other known causes of osteonecrosis (claim 20).
Hill et al. teach treating or regenerating tissue that can be as a results of osteonecrosis comprising using a bioactive hydrogel matrix comprising polypeptide, such as gelatin (see abstract, paragraph [0003]). They teach that the bioactive hydrogel resulted greater than 20-fold increase in bone morphogenic protein (BMP-2) (see paragraph [0085]). They teach that the bioactive hydrogel further comprises at least one osteoinductive material, wherein the osteoinductive material comprises BMPs (that includes BMP-2, BMP-7), FGFs or vascular endothelial growth factors (VEGFs), collagen (see paragraph [0104], claim 36, 98). Hill et al. do not teach a gelatin tyramine comprising a BMP or VEGF for treating Legg-Valve Perthes disease.
Lehenkari et al. do not teach to administer hydrogels comprising a growth factor to promote bone growth.
Li et al. teach an injectable gelatin derivative hydrogels with vascular endothelial growth factor (see Title, abstract). They teach gelatin-derived hydrogels that releases growth factor. Regarding claims 11-12,15,17, they teach tyramine modified gelatin provides cross-linked hydrogel and heparin in gelatin matrix where they incorporated VEGF, wherein VEGF binding to heparin stabilizes and release in sustained manner (abstract). They teach measuring VEGF release from the hydrogel at 37 °C (see pg. 91). Regarding claim 13, they teach that the gelatin time is measured in PBS at pH about 7.4 (which is physiologic solution would be considered as isotonic) (see pg. 91, left col. 2.6-2.7 injectable hydrogel preparation). They teach the composition comprises hydrogen peroxide (H2O2) because gelatin-derived solution is mixed with hydrogen peroxide (pg. 89, left col. last line).
Lehenkari et al teach bone disease such as Legg-Calve-Perthes Disease by using a bone drill made by superplastic to drill femur head and an angle for a medical treatment (see paragraph [0028], [0056]). They teach that there is no vascular veins extending through epiphyseal line and the head of femur is therefore dependent on its own vascularization fails and causing the disease condition. They teach drilling through epiphyseal plate makes it possible achieve revascularization
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to treat an osteonecrosis disease including Legg-Calve-Perthes Disease as taught by Lehenkari et al. comprising gelatin-matrix tyramine and a growth factor VEGF as taught by Li et al and to further comprise one or more osteoinductive material as taught by Hill et al for treating osteonecrosis diseases. Additionally, one would have been motivated to do so because Hill et al teach radiation induced osteonecrosis using a hydrogel comprising a growth factor and Li et al teach gelatin tyramine hydrogel formulated with VEGF can induce angiogenesis. Further, one would have a reasonable expectation of success in treating osteonecrosis diseases by administering a hydrogel as taught by Hill et al and by Li et al for promoting bone growth. Therefore, the instantly claimed invention would have been obvious over the combined teaching of the prior art.
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.
Claims 11-14, and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 8-16 and 20-21 of U.S. Patent No. 10,758,253. Although the claims at issue are not identical, they are not patentably distinct from each other because a composition comprising at least one of autologous bone marrow, autologous bone stem cells, bone growth material, osteoinductive material, BMP-2, bone morphogenic protein infused in collagen matrix, wherein washing fluid cleans at least 50, 60, 70,75, 80, 85 or 90% of the volume within the bone are taught in claims 1-6, 8-16 and 20-21 of U.S. Patent No. 10,758,253.
Claims 11-15, 17, 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 and 20-21 of U.S. Patent No. 10,758,253 in view of Li et al. (Acta Biomaterialia, 13: 88-100, (2015)).
Claims 1-6, 8-16 and 20-21 of U.S. Patent No. 10,758,253 teach a method of treating osteonecrosis disease comprising drilling two holes, inserting a needle or cannula to a first hole to wash with a washing fluid to remove dead cell debris, necrotic marrow fat, or inflammatory factor and introducing bone growth promoting material into the bone, wherein the washing fluid comprises biocompatible isotonic fluid and optionally comprises detergent, surfactant, antibiotic, alcohol, preservative or a combination thereof, wherein inserting bone growth material further comprises injecting with at least one of autologous bone marrow, autologous bone stem cells, bone growth material, osteoinductive material, BMP-2, bone morphogenic protein infused in collagen matrix, wherein washing fluid cleans at least 50, 60, 70,75, 80, 85 or 90% of the volume within the bone. Claims 1-6, 8-16 and 20-21 of U.S. Patent No. 10,758,253 do not teach gelatin tyramine matrix comprising a bone growth agent for treating osteonecrosis.
Li et al. teach an injectable gelatin derivative hydrogels with vascular endothelial growth factor (see Title, abstract). They teach gelatin-derived hydrogels that releases growth factor. Regarding claims 11-12,15,17, they teach tyramine modified gelatin provides cross-linked hydrogel and heparin in gelatin matrix where they incorporated VEGF, wherein VEGF binding to heparin stabilizes and release in sustained manner (abstract). They teach measuring VEGF release from the hydrogel at 37 °C (see pg. 91). Regarding claim 13, they teach that the gelatin time is measured in PBS at pH about 7.4 (which is physiologic solution would be considered as isotonic) (see pg. 91, left col. 2.6-2.7 injectable hydrogel preparation). They teach the composition comprises hydrogen peroxide (H2O2) because gelatin-derived solution is mixed with hydrogen peroxide (pg. 89, left col. last line).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use a composition comprising gelatin-matrix tyramine and a growth factor VEGF as taught by Li et al for treating osteonecrosis diseases as taught by claims 1-6, 8-16 and 20-21 of U.S. Patent No. 10,758,253. Additionally, one would have been motivated to do so because Li et al teach gelatin tyramine hydrogel formulated with VEGF can induce angiogenesis in bone diseases. Further, one would have a reasonable expectation of success in treating osteonecrosis diseases by administering a hydrogel as taught by Li et al for promoting bone growth. Therefore, the instantly claimed invention would have been obvious over the combined teaching of the prior art.
Conclusion
No claim is allowed.
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/GYAN CHANDRA/Primary Examiner, Art Unit 1674
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