DETAILED ACTION
Receipt is acknowledged of applicant’s Amendment/Remarks filed June 12, 2026.
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 .
Status of the Claims
Claims 1 and 19 have been amended. Claims 5, 7, 9, 20 and 24-27 are cancelled. No claims are newly added. Accordingly, claims 1-4, 6, 8, 10-19, 21-23, 28 and 29 remain pending in the application and are currently under examination.
Information Disclosure Statement
The IDS’s dated 6/25/2026 and 7/27/2026 have been considered. The previous IDS dated 9/17/2025 has also been reconsidered as a copy of the reference of citation C1 has been provided. Signed copies are enclosed herewith.
Withdrawn Objections/Rejections
Applicant’s amendment renders the objections to claims 1 and 9 moot. Specifically, the claims have been amended to remedy the minor informalities. Thus, said objections have been withdrawn.
Applicant’s amendment renders the rejections under 35 USC 112(b) moot. Specifically, claim 1 has been amended to remedy the antecedent basis issue and claims 25 and 26 have been cancelled. Thus, said rejections have been withdrawn.
Applicant’s amendment renders the rejections under 35 USC 112(d) moot. Specifically, claims 24 and 25 have been cancelled. Thus, said rejections have been withdrawn.
Response to Declaration under 37 CFR 1.132
The declaration under 37 CFR 1.132 filed June 12, 2026 is insufficient to overcome the rejection of claims 1, 6, 12-14, 19, 22 and 24 based upon Thakur, Benedict and UTHealth, the rejection of claims 2-4, 10 and 11 based upon Thakur, Benedict, UTHealth, McKay and Krishnan, the rejection of claims 8, 17, 18 and 29 based upon Thakur, Benedict, UTHealth and Guo, the rejection of claim 15 based upon Thakur, Benedict, UTHealth and UVA, the rejection of claim 16 based upon Thakur, Benedict, UTHealth and Walker, the rejection of claim 21 based upon Thakur, Benedict, UTHealth and Reves, the rejection of claims 23, 25 and 26 based upon Thakur, Benedict, UTHealth and Bhaduri, the rejection of claim 28 based upon Thakur, Benedict, UTHealth and Sullivan as set forth in the last Office action because the evidence provided a) does not compare the claimed subject matter with the closest prior art (MPEP 716.02(e)) and b) is not commensurate in scope with the claimed invention (MPEP 716.02(d)). More specifically, applicant asserts that Thakur requires a pre-treatment with osteogenic supplements such as ascorbic-2-phosphate, dexamethasone and β-glycerophosphate prior to initiate and maintain mineral formation in osteoblasts whereas the inventive formulations no not require such a pretreatment (paragraphs 6 and 8 of Declaration). However, the instant claims recite, “a method of treating a patient having a bone defect comprising...” which includes open-ended “comprising” language that allows for additional unrecited steps or elements (MPEP 2111.03(I)). Thus, a pre-treatment step is not excluded from the claimed invention and, as such, the data based on the comparison of including a pre-treatment step and excluding a pre-treatment step is not commensurate in scope with the claimed invention. Additionally, the commercial formations tested (MasterGraft®, Vitoss and AttraX™) comprise calcium phosphate (i.e., beta-tricalcium phosphate and hydroxyapatite) and type-I collagen whereas the present “Formulation + Naloxone” is composed of calcium phosphate salts (i.e., beta-tricalcium phosphate, calcium phosphate dibasic, calcium phosphate tribasic, hydroxyapatite, and calcium oxide), type-I collagen, and excipients that include an iron excipient, namely iron (III) sulfate, magnesium oxide, sodium carbonate, sodium phosphate and ascorbic acid as well as naloxone (paragraph 8 of Declaration). Thakur, as discussed in the rejection, teaches methods for promoting bone formation by locally administering a composition containing naloxone or salts thereof with a carrier (e.g., powdered collagen, beta tricalcium phosphate) in the form of a paste or putty. The composition of Thakur is not similar to that of the “commercial formulations” tested because Thakur includes naloxone whereas the commercial formulations do not include naloxone. Accordingly, the data provided does not compare the closest prior art. For these reasons, the Declaration is ineffective in overcoming said 103 rejections.
Maintained Rejections
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.
Claims 1, 6, 12-14, 19 and 22 stand rejected under 35 U.S.C. 103 as being unpatentable over Thakur et al. (US 2015/0344882 A1, Dec. 3, 2015, hereafter as “Thakur”) in view of Benedict et al. (CA 2280966 C, Apr. 17, 2012, hereafter as “Benedict”) and UTHealth Neurosciences (“Spinal Fusion for Severe Back Pain”, Nov. 25, 2020, hereafter as “UTHealth”).
The claimed invention is drawn to a method of treating a patient having a bone defect comprising locally administering at a site of a vertebral bone disease in the patient a composition consisting of (a) dry slurry consisting of (i) a calcium phosphate, and (ii) at least one of the following: a hardening agent, an agent that controls the rate of curing, an acidifying agent, an iron excipient, and powdered collagen; and (b) a diluent solution consisting of (i) a saline solution, (ii) naloxone or a salt thereof, and (iii) at least one acidifying agent, wherein the dry slurry and the diluent solution are each prepared separately, and subsequently mixed to form the composition, and wherein the acidifying agent in the dry slurry is different from the acidifying gent in the diluent solution.
It is noted that the claimed invention is drawn to a method of treatment comprising local administration of a composition consisting of a dry slurry and a diluent solution. The instant specification indicates that the dry slurry (powder) and diluent solution are mixed together to form a paste, putty or otherwise amorphous solid composition that is applied directly and locally to a site of bone injury or surgical intervention ([111], [112], [148] and [157]). In light of the specification, the examiner is interpreting the claimed composition to be a paste, putty or otherwise amorphous solid containing a a) calcium phosphate, b) at least one of the following: a hardening agent, an agent that controls the rate of curing, an acidifying agent, an iron excipient, and powdered collagen, c) saline, d) naloxone or a salt thereof, and e) at least one acidifying agent (different from the optional acidifying agent). It is also noted that the limitation, “wherein the dry slurry and the diluent solution are each prepared separately, and subsequently mixed to form the composition” is being interpreted as a product by process limitations. Any structure implied by the process steps is considered, however the process steps in which the product is made is not a factor in determining the patentability of the method of using the composition.
Regarding instant claims 1, 6 and 19, Thakur teaches compositions and methods for promoting bone formation in bone defects and spinal fusion procedures (title; [0029]-[0031]). Thakur teaches that inhibition of the opioid growth factor signaling through the opioid growth factor receptor (OGFR) is effective to promote bone formation and/or reduce bone destruction and local administration of said OGFR to the site where bone formation is desired leads to an increase in mineralization and an increase in bone formation ([0014]). Thakur teaches the particular OGFR binding antagonist, naloxone and salts thereof ([0034]-[0035]). Thakur teaches that an OGFR antagonist can be administered with or without a carrier locally to accelerate repair or promote fusion of a vertebral bone and teaches the particular carriers, collagen including powdered collagen and beta tricalcium phosphate ([0045]-[0047] and [0053]; instant claims 1 and 19). Thakur further teaches that the powdered collagen can be reconstituted with sterile saline ([0051]). Thakur teaches that the carrier can be in the form of a putty or a paste ([0051] and [0053]). Thakur teaches that the OGFR antagonist can be formulated to be released in a controlled manner over a period of time ([0048]-[0050] and [0054]; instant claim 6). Thakur also teaches suitable dosages of naloxone ([0058]).
Thakur is silent to at least one acidifying agent, wherein the acidifying agents are different from one another (instant claim 1), wherein the acidifying agent is acetic acid (instant claim 22).
Benedict teaches an implantable collagen-containing putty material for the repair of bone defects including spinal fusion procedures (abstract; page 16, lines 7-15; page 17, lines 14-21). Said putty material comprises collagen, water and an acid (e.g., ascorbic acid, acetic acid, citric acid) and can additionally include an active agent (e.g., osteoinductive materials, growth factors, cartilage inducing factors, etc.) (page 2, lines 19-35). Benedict specifically teaches incorporating two different acids (claim 1). Benedict teaches that the putty material has a pH of between about 3 to about 6 because at that pH the material has excellent physical properties, e.g., a putty consistency that is elastic and dough-like and such a consistency is desired because it provides many benefits such an enhanced cohesiveness, ease of handling and moldability (page 5, lines 3-35). Benedict further teaches that the desired pH is achieved by adding the acid in a sufficient amount to achieve said pH range and said physical properties (page 5, line 21 – page 6, line 28).
Thakur and Benedict are drawn to treatments for bone repair including spinal bone repair, thus, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to include one or more different acidifying agents such as acetic acid and ascorbic acid into the invention of Thakur as suggested by Benedict with a reasonable expectation of success. A skilled artisan would have been motivated to do so because Benedict teaches the addition of two different acids to a bone repair composition comprising collagen and water leads to a putty consistency that has excellent physical properties. In light of the teachings of Thakur and Benedict, one of ordinary skill in the art would have reasonably expected a method of treating a bone defect of the spine in a patient comprising administering a bone defect/repair composition such as the one advanced by Thakur and further containing two different acids such as acetic acid and ascorbic acid, as described in Benedict, would effectively provide a bone defect composition having a putty consistency that has excellent physical properties including enhanced cohesiveness, ease of handling and moldability.
While Thakur and Benedict teach treating vertebral bone such as spinal fusion or bone defects, Thakur and Benedict are silent to treating a vertebral bone disease comprising at least one of degenerative disc disease, spondylolisthesis, and spinal instability (instant claims 1 and 12-14).
UTHealth teaches that spinal fusion is a known treatment for severe pain resulting from vertebral fracture, scoliosis, spinal stenosis, degenerative disc disease, spondylolisthesis, and similar conditions by providing stability to the spine by joining two vertebrae together with, e.g., bone grafts, metal plates, and rods (1st and 2nd paragraphs).
Thakur, Benedict and UTHealth are drawn to treatments for spinal bone repair such as spinal fusion, thus, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to treat a patient having a vertebral bone disease such as degenerative disc disease, spondylolisthesis or spinal instability with spinal fusion comprising locally administering a bone graft composition such as the one taught by Thakur/Benedict as suggested by UTHealth with a reasonable expectation of success. A skilled artisan would have been motivated to do so because Thakur and Benedict teach a bone graft composition useful for spinal bone repair including spinal fusion and UTHealth teaches that spinal fusion is a known treatment for degenerative disc disease, spondylolisthesis and providing stability to the spine. In light of the teachings of Thakur, Benedict and UTHealth, one of ordinary skill in the art would have reasonably expected a method of treating a patient having a vertebral bone disease comprising degenerative disc disease, spondylolisthesis, or spinal instability comprising administering a bone graft composition such as the one advanced by Thakur/Benedict would have effectively provided spinal fusion between the affected vertebrae.
Thus, the combined teachings of Thakur, Benedict and UTHealth render the instant claims prima facie obvious.
Response to Arguments
Applicant's arguments, filed 6/12/2026, regarding the 103 rejections over Thakur, Benedict and UTHealth have been fully considered but they are not persuasive.
Applicant argues that any prima facie case of obviousness is more than overcome by surprising and unexpected results provided in the enclosed Rule 132 Declaration by Dr. Bryan Margulies. Applicant asserts that Thakur requires a pre-treatment with osteogenic supplements such as ascorbic-2-phosphate, dexamethasone and β-glycerophosphate prior to initiate and maintain mineral formation in osteoblasts whereas the inventive formulations no not require such a pretreatment. Applicant asserts that the declaration provides evidence that unlike the existing formulation, including the formulations of Thakur, the compositions of this application, which include naloxone and an iron excipient, such as iron (III) sulfate, do not require pre-treatment of a bone defect with osteogenic supplements to initiate and maintain mineral formation in osteoblasts. Remarks, pages 7-11.
In response, it is respectfully submitted that the instant claims recite, “a method of treating a patient having a bone defect comprising...” which includes open-ended “comprising” language that allows for additional unrecited steps or elements (MPEP 2111.03(I)). Thus, a pre-treatment step is not excluded from the claimed invention and, as such, the data based on the comparison of including a pre-treatment step and excluding a pre-treatment step is not commensurate in scope with the claimed invention. Additionally, the commercial formations tested (MasterGraft®, Vitoss and AttraX™) comprise calcium phosphate (i.e., beta-tricalcium phosphate and hydroxyapatite) and type-I collagen whereas the present “Formulation + Naloxone” is composed of calcium phosphate salts (i.e., beta-tricalcium phosphate, calcium phosphate dibasic, calcium phosphate tribasic, hydroxyapatite, and calcium oxide), type-I collagen, and excipients that include an iron excipient, namely iron (III) sulfate, magnesium oxide, sodium carbonate, sodium phosphate and ascorbic acid as well as naloxone. The claims recite, “at least one of the following: a hardening agent, an agent that controls the rate of curing, an acidifying agent, an iron excipient, and powdered collagen” (emphasis added). In the broadest sense, the claim requires only one of the listed ingredients. The iron excipient that applicant asserts as a component of the instant composition is not a required element in independent claim 1. If an iron excipient is a critical component of the invention and plays a critical role in the asserted unexpected results, the claims should be amended to reflect that said component is required. Thakur, as discussed in the rejection, teaches methods for promoting bone formation by locally administering a composition containing naloxone or salts thereof with a carrier (e.g., powdered collagen, beta tricalcium phosphate) in the form of a paste or putty. The composition of Thakur is not similar to that of the “commercial formulations” tested because Thakur includes naloxone whereas the commercial formulations do not include naloxone. Thus, the evidence provided a) does not compare the claimed subject matter with the closest prior art (MPEP 716.02(e)) and b) is not commensurate in scope with the claimed invention (MPEP 716.02(d)).
For these reasons, the Declaration is ineffective in overcoming said 103 rejection.
Thus, for these reasons, Applicant’s arguments are found unpersuasive. Said rejection is maintained.
Claims 2-4, 10 and 11 stand rejected under 35 U.S.C. 103 as being unpatentable over Thakur et al. (US 2015/0344882 A1, Dec. 3, 2015, hereafter as “Thakur”) in view of Benedict et al. (CA 2280966 C, Apr. 17, 2012, hereafter as “Benedict”) and UTHealth Neurosciences (“Spinal Fusion for Severe Back Pain”, Nov. 25, 2020, hereafter as “UTHealth”), as applied to claim 1 above, and further in view of McKay et al. (US 2014/0341964 A1, Nov. 20, 2014, hereafter as “McKay”) as evidenced by Krishnan et al. (“Bioglass: A novel biocompatible innovation”, J Adv Pharm Tech Res 2013;4:78‑83; hereafter as “Krishnan”).
The invention is described above.
Thakur, Benedict and UTHealth teach the elements discussed above.
Thakur, Benedict and UTHealth are silent to “the calcium phosphate comprises biphasic calcium phosphate particles” (instant claim 2), “wherein the biphasic calcium phosphate particles comprise hydroxyapatite and tricalcium phosphate” (instant claim 3), “wherein the biphasic calcium phosphate particles comprise about 20-60% hydroxyapatite and about 40-80% tricalcium phosphate (instant claim 4), “bioglass” (instant claim 10), and calcium oxide (instant claim 11).
McKay teaches an implantable osteogenic putty comprising mineral particles and collagen for the purpose of treating bone voids (abstract; [0005]-[0006]). McKay teaches that the mineral particles can be selected from bone particles, Bioglass®, tricalcium phosphate, biphasic calcium phosphate, hydroxyapatite, coralline hydroxyapatite, and biocompatible ceramics ([0025]). McKay teaches that biphasic calcium phosphate is preferred and that the biphasic calcium phosphate is composed of tricalcium phosphate to hydroxyapatite in a ratio of about 50:50 to about 95:5, more preferably about 70:30 to about 95:5 and even more preferably about 80:20 to about 90:10 ([0025]). It is noted that Bioglass® contains calcium oxide as evidenced by Krishnan (page 79, 2nd full para.; Table 1).
Thakur, Benedict and McKay are drawn to compositions for the repair of bone defects/voids, thus, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to include a biphasic calcium phosphate mineral component composed of tricalcium phosphate to hydroxyapatite in the ratios taught by McKay alone or in combination with Bioglass® (which necessarily includes calcium oxide) with a reasonable expectation of success. A skilled artisan would have been motivated to do so because McKay effectively teaches said mineral components (in said ratios) are functional equivalents of one another (MPEP 2144.06) and are suitable for the same purpose (MPEP 2144.07). Substituting or combining equivalents known for the same purpose is prima facie obvious.
It would have further been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to optimize the ratio of tricalcium phosphate to hydroxyapatite by way of routine optimization with a reasonable expectation of success. 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”. MPEP 2144.05(II)(A) also states, “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical... [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”. As discussed above, McKay teaches ratio ranges that significantly overlap with the claimed ranges. A skilled artisan would have been motivated to optimize the ranges taught by McKay because it is “the normal desire of scientists or artisans to improve upon what is already generally known” and “determine where in a disclosed set of percentage ranges is the optimum combination of percentages” (MPEP 2144.05(II)(A)).
Thus, the combined teachings of Thakur, Benedict, UTHealth and McKay render the instant claims prima facie obvious.
Response to Arguments
Applicant's arguments, filed 6/12/2026, regarding the 103 rejection over Thakur, Benedict, UTHealth and McKay have been fully considered but they are not persuasive.
Applicant relies on the same arguments as presented for the 103 rejection over Thakur, Benedict and UTHealth. No further arguments regarding claims 2-4, 10 and 11 are presented. Remarks, pages 7-11.
For the same reasons as discussed above, Applicant’s arguments are not persuasive.
Claims 8, 17, 18 and 29 stand rejected under 35 U.S.C. 103 as being unpatentable over Thakur et al. (US 2015/0344882 A1, Dec. 3, 2015, hereafter as “Thakur”) in view of Benedict et al. (CA 2280966 C, Apr. 17, 2012, hereafter as “Benedict”) and UTHealth Neurosciences (“Spinal Fusion for Severe Back Pain”, Nov. 25, 2020, hereafter as “UTHealth”), as applied to claim 1 above, and further in view of Guo et al. (CN 104803674 A, machine translation, Jul. 29, 2015, hereafter as “Guo”).
The invention is described above.
Thakur, Benedict and UTHealth teach the elements discussed above including the limitations of instant claim 1.
Thakur, Benedict and UTHealth are silent to the claimed iron excipients of instant claims 8 and 29 (e.g., iron (III) sulfate hydrate), the iron excipient in an amount effective for increasing bone formation (instant claim 17), and between 5% and 12% of iron (III) sulfate (instant claim 18). It is noted that the instant specification recites, “iron (III) sulfate hydrate (Fe2(SO4)3)” ([92]) effectively defining iron (III) sulfate hydrate as the compound Fe2(SO4)3 which also known as iron (III) sulfate.
Guo teaches an implantable calcium phosphate iron bioceramic composition comprising 10-18 parts of ferric sulfate (composition has 84-133 total parts) (abstract; page 3, lines 10-20). Converting parts to percentages, ferric sulfate is present in amounts between 7.5% to 21% by weight of the total composition. Said composition has the function of promoting bone growth, slow release of calcium, phosphorous and iron, improved mechanical properties and is an ideal bone substitute (abstract). It is noted that ferric sulfate is synonymous with “iron (III) sulfate”.
The references are drawn to calcium phosphate-based compositions for the repair of bone defects/voids, thus, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to include an iron excipient such as ferric sulfate into the invention Thakur/Benedict/UTHealth as suggested by Guo with a reasonable expectation of success. A skilled artisan would have been motivated to do so because Guo teaches that the inclusion of said iron excipients including ferric sulfate in amounts of 7.5-21% is suitable for implantable bone repair compositions (MPEP 2144.07). One of ordinary skill in the art would have reasonably expected a bone repair composition further comprising iron. It is noted, “In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists” (MPEP 2144.05). It is also noted, “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. ‘[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.’” (MPEP 2144.05). It is further noted that while the reference does not explicitly teach that the iron excipient itself increases bone formation, the reference teaches an overlapping amount of an iron excipient and MPEP 2112.01 states, “Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established”.
Thus, the combined teachings of Thakur, Benedict, UTHealth and Guo render the instant claims prima facie obvious.
Response to Arguments
Applicant's arguments, filed 6/12/2026, regarding the 103 rejection over Thakur, Benedict, UTHealth and Guo have been fully considered but they are not persuasive.
Applicant relies on the same arguments as presented for the 103 rejection over Thakur, Benedict and UTHealth. No further arguments regarding claims 8, 17, 18 and 29 are presented. Remarks, pages 7-11.
For the same reasons as discussed above, Applicant’s arguments are not persuasive.
Claim 15 stands rejected under 35 U.S.C. 103 as being unpatentable over Thakur et al. (US 2015/0344882 A1, Dec. 3, 2015, hereafter as “Thakur”) in view of Benedict et al. (CA 2280966 C, Apr. 17, 2012, hereafter as “Benedict”) and UTHealth Neurosciences (“Spinal Fusion for Severe Back Pain”, Nov. 25, 2020, hereafter as “UTHealth”), as applied to claim 1 above, and further in view of University of Virginia Health System (“Lumbar Disc Disease, Herniation, and Degeneration”, Aug. 14, 2019, hereafter as “UVA”).
The invention is described above.
Thakur, Benedict and UTHealth teach the elements discussed above.
Thakur, Benedict and UTHealth are silent to wherein the patient further has at least one of disc herniation, decrease disc height, osteophyte formation, ligamentous thickening, facet joint degeneration, foraminal narrowing, or loss of foraminal height (instant claim 15).
UVA teaches that lumbar disc disease frequently starts with degeneration of the disc material, causing a loss of vertebral body height (page 3).
The references are all drawn to spinal repair and UTHealth and UVA are, more specifically, drawn to patients having degenerative disc disease, thus, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to further limit the patient population to patients a loss of vertebral height into the invention Thakur/Benedict/UTHealth as suggested by UVA with a reasonable expectation of success. A skilled artisan would have been motivated to do so because UVA teaches that patients having degenerative disc disease, specifically lumbar disc disease, encompasses patients having a loss of vertebral height.
Thus, the combined teachings of Thakur, Benedict, UTHealth and UVA render the instant claim prima facie obvious.
Response to Arguments
Applicant's arguments, filed 6/12/2025, regarding the 103 rejection over Thakur, Benedict, UTHealth and UVA have been fully considered but they are not persuasive.
Applicant relies on the same arguments as presented for the 103 rejection over Thakur, Benedict and UTHealth. No further arguments regarding claim 15 are presented. Remarks, pages 7-11.
For the same reasons as discussed above, Applicant’s arguments are not persuasive.
Claim 16 stands rejected under 35 U.S.C. 103 as being unpatentable over Thakur et al. (US 2015/0344882 A1, Dec. 3, 2015, hereafter as “Thakur”) in view of Benedict et al. (CA 2280966 C, Apr. 17, 2012, hereafter as “Benedict”) and UTHealth Neurosciences (“Spinal Fusion for Severe Back Pain”, Nov. 25, 2020, hereafter as “UTHealth”), as applied to claim 1 above, and further in view of Walker (USPN 8,515,782 B2, Aug. 20, 2013, hereafter as “Walker”).
The invention is described above.
Thakur, Benedict and UTHealth teach the elements discussed above.
Thakur, Benedict and UTHealth are silent to wherein S-radiographs of the patient during flexion/extension movement show angulation ≥ 5 degrees and/or translation ≥ 4 mm of the affected vertebral bone(s) (instant claim 16).
Walker teaches a patient that is unable to heel toe walk with 20 degrees flexion of the lumbar spine with pain and 10 degrees extension with pain (col. 26, lines 19-32). Said patient is diagnosed with lumbar degenerative disc disease (col. 26, lines 19-32).
The references are all drawn to spinal repair and UTHealth and Walker are, more specifically, drawn to patients having degenerative disc disease, thus, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to further limit the patient population to patients having ≥ 5 degrees flexion/extension movement and/or ≥ 4 mm translation into the invention Thakur/Benedict/UTHealth as suggested by Walker with a reasonable expectation of success. A skilled artisan would have been motivated to do so because Walker teaches that patients having degenerative disc disease encompasses patients having 20 degrees flexion and 10 degrees extension.
Thus, the combined teachings of Thakur, Benedict, UTHealth and Walker render the instant claim prima facie obvious.
Response to Arguments
Applicant's arguments, filed 6/12/2025, regarding the 103 rejection over Thakur, Benedict, UTHealth and Walker have been fully considered but they are not persuasive.
Applicant relies on the same arguments as presented for the 103 rejection over Thakur, Benedict and UTHealth. No further arguments regarding claim 16 are presented. Remarks, pages 7-11.
For the same reasons as discussed above, Applicant’s arguments are not persuasive.
Claim 21 stands rejected under 35 U.S.C. 103 as being unpatentable over Thakur et al. (US 2015/0344882 A1, Dec. 3, 2015, hereafter as “Thakur”) in view of Benedict et al. (CA 2280966 C, Apr. 17, 2012, hereafter as “Benedict”) and UTHealth Neurosciences (“Spinal Fusion for Severe Back Pain”, Nov. 25, 2020, hereafter as “UTHealth”), as applied to claim 1, and further in view of Reves et al. (US 2018/0353654 A1, Dec. 13, 2018, hereafter as “Reves”).
The invention is described above.
Thakur, Benedict and UTHealth teach the elements discussed above including the limitations of instant claims 1 and 19.
Thakur, Benedict and UTHealth are silent to powdered collagen in an amount of 18-24% (instant claim 21).
Reves teaches an implantable bone defect composition to promote bone growth (abstract). Reves teaches the composition is specifically useful in subjects with spinal disorders including degenerative disc disease or arthritis affecting the lumbar or cervical vertebrae ([0248]). Reves teaches that the composition comprises collagen particles on the micron scale (powder) ([0151]) in amounts of about 5-25% (abstract; [0015]) as well as mineral particles such as tricalcium phosphate and hydroxyapatite ([0182]).
The references are drawn to compositions and methods for the repair of the spine, thus, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to include powdered collagen in the claimed amounts as suggested by Reves into the invention of Thakur/Benedict/UTHealth with a reasonable expectation of success. A skilled artisan would have been motivated to do so because Reves teaches the inclusion of powdered collagen in amounts of about 5-25% are suitable for implantable bone defect compositions for the specific purpose of treating spinal disorders and promoting bone growth (MPEP 2144.07). Furthermore, 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”. MPEP 2144.05(II)(A) also states, “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical... [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.” As discussed above, Reves teaches a collagen percentage range that encompasses/significantly overlaps with the claimed range. A skilled artisan would have been motivated to optimize the ranges taught by Reves because it is “the normal desire of scientists or artisans to improve upon what is already generally known” and “determine where in a disclosed set of percentage ranges is the optimum combination of percentages” (MPEP 2144.05(II)(A)).
Thus, the combined teachings of Thakur, Benedict, UTHealth and Reves render the instant claim prima facie obvious.
Response to Arguments
Applicant's arguments, filed 6/12/2025, regarding the 103 rejection over Thakur, Benedict, UTHealth and Reves have been fully considered but they are not persuasive.
Applicant relies on the same arguments as presented for the 103 rejection over Thakur, Benedict and UTHealth. No further arguments regarding claim 21 are presented. Remarks, pages 7-11.
For the same reasons as discussed above, Applicant’s arguments are not persuasive.
Claim 23 stands rejected under 35 U.S.C. 103 as being unpatentable over Thakur et al. (US 2015/0344882 A1, Dec. 3, 2015, hereafter as “Thakur”) in view of Benedict et al. (CA 2280966 C, Apr. 17, 2012, hereafter as “Benedict”) and UTHealth Neurosciences (“Spinal Fusion for Severe Back Pain”, Nov. 25, 2020, hereafter as “UTHealth”), as applied to claims 1 and 22 above, and further in view of Bhaduri et al. (US 2015/0005392 A1, Jan. 1, 2015, hereafter as “Bhaduri”).
The invention is described above.
Thakur, Benedict and UTHealth teach the elements discussed above.
Thakur, Benedict and UTHealth are silent to citric acid monohydrate (instant claim 23).
Bhaduri teaches calcium phosphate-based compositions for bone repair including spinal fusions (abstract; [0006], [0009], [0039], [0051] and [0072]). Bhaduri teaches said compositions can be in putty or paste forms (abstract; [0055] and [0072]). Bhaduri teaches that the composition comprises a setting solution that contains citric acid monohydrate, wherein the citric acid monohydrate improves the handling of the final paste ([0043]).
The references are all drawn to compositions and methods for bone repair including spinal fusion, thus, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to further include citric acid monohydrate into the invention Thakur/Benedict/UTHealth as suggested by Bhaduri with a reasonable expectation of success. A skilled artisan would have been motivated to do so because Benedict and Bhaduri teach acidic components that are both taught as improving handling properties of a bone repair putty/paste composition and “it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose” (MPEP 2144.06(I)).
Regarding the amounts of the individual ingredients claimed in instant claims 25 and 26, said claims attempt to limit the amounts of the ingredients in terms of the diluent solution. As explained above, the claim recites, “a composition consisting of a dry slurry… and a diluent solution…” and the specification discloses that the dry slurry and the diluent form a putty, a paste, or otherwise amorphous solid composition. The claim is not drawn to a method of making the composition and, as such, the presence of said components in the composition as a whole reads on the ingredients as claimed. Additionally, in view of the 112(b) rejection above, there is no indication of how much of each of the components is present in terms of the composition as a whole. It is further noted that the composition suggested by the prior art does not require any additional components excluded from the claims. Furthermore, Thakur teaches a suitable dosage range of naloxone is 400 ng/mL (1 µM) to 400 µg/mL (1 mM) for increasing bone formation and/or decrease bone degradation through decreased osteoclast formation ([0058]). Benedict teaches that the amount of acid (e.g., acetic acid, citric acid) present is from about 0.05 equivalent mmole (eq. mmol) of acid per 100 mg of collagen to about 2.30 eq. moll of acid per 100 mg of collagen (page 6, lines 8-28). Bhaduri exemplifies calcium acid monohydrate in an amount of 0.0032 g ([0064]). While the references do not explicitly recite percentages of each ingredient, it would have further been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to optimize the amounts of acetic acid, citric acid monohydrate, and a salt of naloxone by way of routine optimization with a reasonable expectation of success. MPEP 2144.05(II)(A) states, “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical... [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”. As discussed above, the references teach suitable amounts of each ingredient and a skilled artisan would have been motivated to optimize the amounts taught by the prior art because it is “the normal desire of scientists or artisans to improve upon what is already generally known” and “determine where in a disclosed set of percentage ranges is the optimum combination of percentages” (MPEP 2144.05(II)(A)).
Thus, the combined teachings of Thakur, Benedict, UTHealth and Bhaduri render the instant claim prima facie obvious.
Response to Arguments
Applicant's arguments, filed 6/12/2025, regarding the 103 rejection over Thakur, Benedict, UTHealth and Bhaduri have been fully considered but they are not persuasive.
Applicant relies on the same arguments as presented for the 103 rejection over Thakur, Benedict and UTHealth. No further arguments regarding claim 23 is presented. Claims 25 and 26 have been cancelled. Remarks, pages 7-11.
For the same reasons as discussed above, Applicant’s arguments are not persuasive.
Claim 28 stands rejected under 35 U.S.C. 103 as being unpatentable over Thakur et al. (US 2015/0344882 A1, Dec. 3, 2015, hereafter as “Thakur”) in view of Benedict et al. (CA 2280966 C, Apr. 17, 2012, hereafter as “Benedict”) and UTHealth Neurosciences (“Spinal Fusion for Severe Back Pain”, Nov. 25, 2020, hereafter as “UTHealth”), as applied to claim 1 above, and further in view of Sullivan et al. (“Association of spinal instability due to metastatic disease with increased mortality and a proposed clinical pathway for treatment”, J Neurosurg Spine 32:950–957, June 2020, hereafter as “Sullivan”).
The invention is described above.
Thakur, Benedict and UTHealth teach the elements discussed above.
Thakur, Benedict and UTHealth are silent to the bone defect is caused by cancer (instant claim 28).
Sullivan teaches that spinal instability can be caused by metastatic spine disease (abstract) and spinal fusion procedures are often part of a treatment plan for patients identified as surgical candidates using the Spinal Instability Neoplastic Score (SINS) system (pages 950, 951 and 954).
The references are all drawn to spinal repair including spinal fusion and UTHealth and Sullivan are, more specifically, drawn to patients having spinal instability, thus, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to further limit the patient population to patients having spinal instability caused by cancer into the invention Thakur/Benedict/UTHealth as suggested by Sullivan with a reasonable expectation of success. A skilled artisan would have been motivated to do so because Sullivan teaches that patients having spinal instability caused by cancer can be treated with spinal repair surgery such as a spinal fusion procedure.
Thus, the combined teachings of Thakur, Benedict, UTHealth and Sullivan render the instant claim prima facie obvious.
Response to Arguments
Applicant's arguments, filed 6/12/2025, regarding the 103 rejection over Thakur, Benedict, UTHealth and Sullivan have been fully considered but they are not persuasive.
Applicant relies on the same arguments as presented for the 103 rejection over Thakur, Benedict and UTHealth. No further arguments regarding claim 28 are presented. Remarks, pages 7-11.
For the same reasons as discussed above, Applicant’s arguments are not persuasive.
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 1-4, 6, 8, 10-19, 21-23, 28 and 29 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 12,390,551 B2.
Although the claims at issue are not identical, they are not patentably distinct from each other because the subject matter of the instant claims and the subject matter of the patented claims are significantly overlapping.
The instant claims are drawn to a method of treating a patient having a bone defect comprising locally administering at a site of the vertebral bone disease in the patient a composition consisting of (a) dry slurry consisting of (i) a calcium phosphate, and (ii) at least one of the following: a hardening agent, an agent that controls the rate of curing, an acidifying agent, an iron excipient, and powdered collagen; and (b) a diluent solution consisting of (i) a saline solution, (ii) naloxone or a salt thereof, and (iii) at least one acidifying agent, wherein the dry slurry and the diluent solution are each prepared separately, and subsequently mixed to form the composition, and wherein the acidifying agent in the dry slurry is different from the acidifying gent in the diluent solution.
The patented claims are drawn to a method of treating a patient having a cancer selected from the group consisting of lung cancer, breast cancer and prostate cancer, comprising identifying a bone defect in the patient caused by the cancer or resulting from treatment of the cancer, locally administering at the site of the bone defect in the cancer patient in need thereof a composition consisting of a calcium phosphate, an OGFR antagonist, an iron excipient, an optional curing agent, and at least one of the following: an acidifying agent, collagen, and a diluent saline solution, wherein the composition provides a therapeutically effective amount of the iron excipient that increases mineral formation at the site of the bone defect, and wherein the iron excipient is iron (III) sulphate. The patented claims also recite the particular OGFR antagonist, naloxone (claim 13) and the acidifying agent is at least one (implies more than one is permitted) of ascorbic acid, magnesium citrate, potassium citrate, sodium citrate, citric acid monohydrate and acetic acid (claim 7).
While the patented claims do not require an acidifying agent or diluent solution, the patented claims indicate that said ingredients can be optionally included. Accordingly, it would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to include at least one acidifying agent and a diluent solution with a reasonable expectation of success. A skilled artisan would have been motivated to do so because the patent teaches said ingredients are suitable to be included in the formulation for the purpose of treating bone defects in cancer patients.
Thus, the subject matter of the instant claims and the subject matter of the patented claims are not patentably distinct from each other.
Response to Arguments
Applicant's arguments, filed 6/12/2025, regarding the double patenting rejection over USPN 12,390,551 have been fully considered but they are not persuasive.
Applicant acknowledges the rejection and essentially requests that the rejection be held in abeyance until allowable subject matter is indicated. Remarks, page 11.
In response, it is respectfully submitted that applicant’s request is acknowledged. The rejection is still applicable and maintained, at this time.
Claims 1-4, 6, 8, 10-19, 21-23, 28 and 29 stand provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of copending Application No. 19/280749 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the subject matter of the instant claims and the subject matter of the patented claims are significantly overlapping.
The instant claims are described above.
The copending claims are drawn to a composition that increases mineral formation at a site of a bone defect in a cancer patient caused by the cancer or resulting from treatment of the cancer, which is in a moldable form that is formed by mixing together (a) a dry slurry consisting of (i) a calcium phosphate,(ii) iron (III) sulfate, and at least one of the following: a hardening agent, an agent that controls the rate of curing, and powdered collagen; and (b) a liquid solution consisting of (i) a saline diluent solution and two acidifying agents and (ii) an OGFR antagonist derived from oxymorphone that is diluted in the diluent solution. The copending claims further recite that the OGFR antagonist derived from oxymorphone is naloxone (claim 9) and the acidifying agents are selected from ascorbic acid, magnesium citrate, potassium citrate, sodium citrate, citric acid monohydrate and acetic acid (claim 7).
While the copending claims are drawn to a composition and the instant claims are drawn to a method of the using a composition, the copending claims recite the purpose of the composition as increases mineral formation at a site of a bone defect in a cancer patient caused by the cancer or resulting from treatment of the cancer. Thus, it would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to locally administer the copending composition to accomplish the purpose of increasing mineral formation at a site of a bone defect in a cancer patient caused by the cancer or resulting from treatment of the cancer with a reasonable expectation of success. A skilled artisan would have been motivated to do so because the copending application teaches that the composition is suitable for treating bone defects in cancer patients by increasing mineral formation at the site of said bone defect.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments, filed 6/12/2025, regarding the double patenting rejection over USPA 19/280,749 have been fully considered but they are not persuasive.
Applicant acknowledges the rejection and essentially requests that the rejection be held in abeyance until allowable subject matter is indicated. Remarks, page 11.
In response, it is respectfully submitted that applicant’s request is acknowledged. The rejection is still applicable and maintained, at this time.
Conclusion
All claims have been rejected; no claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CASEY HAGOPIAN whose telephone number is (571)272-6097. The examiner can normally be reached on M-F 9:00 am - 5:00 pm.
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Casey S. Hagopian
Examiner, Art Unit 1617
/CARLOS A AZPURU/Primary Examiner, Art Unit 1617
Prosecution Insights