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 .
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.
Election/Restrictions
Applicant's election with traverse of Group I (claims 1-15) in the reply filed on 12/14/23 was previously acknowledged. The traversal is on the grounds that that the subject matter of Group II (claims 16 and 33) is excluded. Claim 16 was amended to depend from claim 1 and thus includes all the features of claim 1 (claim 33 was canceled).
This argument was considered and found persuasive. The restriction requirement between Group I and Group II was withdrawn and claim 16 examined.
Election was made without traverse of BMP-2 and anti-cancer agent.
The requirement between Groups I/II and III/IV was still deemed proper and was made FINAL.
In the reply filed 7/29/24, Applicants amended claims 1, 15 and 35. Claims 2, 8, 14 and 18-33 were canceled.
In the RCE filed 3/14/25, Applicants amended claims 1, 3-4, 6 and 15 were amended.
In the reply filed 9/30/25, Applicants amended claims 1, 3 and 15.
In the reply filed 4/23/26, Applicants did not amend or cancel any claims.
Claims 1, 3-7, 9-13, 15-17 and 34-35 are pending. Please note that claim 5 is rejoined.
Claims 7, 9-13, 17 and 34-35 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim.
Claims 1, 3-6, and 15-16 read on the elected Group I/II and elected species and are under consideration.
Claim Rejections - 35 USC § 103-Maintained
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.
The rejection of claims 1, 3-6 and 16 under 35 U.S.C. 103 as being unpatentable over Zheng et al. (US2014/0288271) in view of Murphy et al. (Acta Biomaterialia 10(2014) 2250-2258,previously provided) as evidenced by Hydroxyapatite - American Chemical Society (accessed 1/16/26) is maintained.
Zheng et al. teach embodiments of the subject invention are directed to collagen membrane, coverings, coatings and/or scaffolds which are particularly suitable for implantable medical devices, and methods of making and using the same in animal or human patients [0065]. The collagen membrane, scaffold or covering of fibers can be configured to substantially encase the target implantable device or may cover only a portion thereof [0091].
With respect to the limitation “wherein greater than 80% of collagen in the collagen containing membrane is type I collagen”, Zheng et al. teach a collagen membrane comprising greater than 80% (w/w) type 1 collagen bundles [0034,0081].
With respect to the limitation “having a thickness ranging from 25 µm to 200 µm, Zheng et al. µm In some embodiments, the collagen membrane of the present invention is about 100 µm thick [0051].
With respect to “wherein a first side of the collagen containing membrane is a smooth surface with compact collagen bundles, and a second side of the collagen containing membrane is a rough and porous surface comprising loose collagen fibers”, Zheng et al. teach Fig.1 wherein the membrane possesses two distinct surfaces, a smooth surface featuring compact collagen bundles (Panel A), and a rough, porous surface of loose collagen fibers (Panel B).
Zheng et al. also teach the composition can contain bone morphogenic proteins and bisphosphonates [0077]. Zheng et al. also teach the collagen membrane for tissue implants such as for the jawbone [0090].
Zheng et al. does not teach the collagen is a “functionalized collagen containing membrane or wherein the drug carrier mixture comprises BMP-2 and a calcium containing carrier mixture. However, the teachings of Murphy et al. cure this deficiency.
Murphy et al. teach collagen-hydroxyapatite (CHA) scaffold comprising BMP-2 and zoledronic acid (ZA) for bone formation (Abstract, Table 1). The CHA scaffold containing BMP-2 meets the limitation of “functionalized collagen-containing membrane” and “calcium containing mixture”. As evidenced by the American Chemical Society, hydroxyapatite, sometimes referred to as durapatite, is a calcium phosphate/hydroxide mineral that occurs naturally in “phosphate rock”. Please note that MPEP 2131.01 states: that an extra reference or evidence can be used to show an inherent characteristic of the thing taught by the primary reference. In the instant case, the reference is relied upon only to establish that hydroxyapatite is a calcium containing carrier mixture.
Murphy et al. teach that CHA demonstrates a capacity for both rhBMP-2 and bisphosphonates binding and delivery, which may make it superior for combination treatment compared to commercially available pure collagen scaffolds. Murphy et al. further teach that the CHA scaffolds demonstrate a capacity for mineralization in the absence of additional osteogenic factors and can be seen as a template for developing multicomponent scaffolds to allow for improved delivery of multiple pharmaceutical or biological agents (p. 2257, last para.).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to modify the scaffold of Zheng et al. to include a drug carrier mixture and a calcium containing mixture as taught by Murphy et al. in order to achieve predictable bone growth effects associated with BMP-2 while retaining the advantageous membrane morphology and handling characteristics taught by Zheng et al. There is a reasonable expectation of success given that Murphy et al. demonstrates binding and controlled release of BMP-2 from collagen-hydroxyapatite systems.
With respect to the limitation “artificial periosteum” in the preamble, please note that MPEP 2111.02 II states "a preamble generally is not limiting when the claim body describes a structurally complete invention such that deletion of the preamble phrase does not affect the structure or steps of the claimed invention." In the instant case, the preamble does not affect the structure. The preamble in this case recites a statement of purpose or use, and therefore was not treated as a claim limitation. Furthermore, the claim body describes a structurally complete invention.
With respect to claims 3-4 and 6, zoledronic acid is a bone active agent that is a bisphosphonate. Murphy et al. teach osteoblast viability in the presence of Collagen, HA was protective (Fig.3). Murphy et al. teach that BMP-2 activates osteoblasts (Fig. 2).
With respect to claim 5, Murphy et al. teach decreased osteoclasts in the presence of ZA (Fig. 7). ZA meets the limitation of bone active agent that inhibits osteoclasts.
With respect to claim 16, the scaffold of Murphy et al. is a hydroxyapatite functionalized collagen membrane.
Response to Arguments
Applicant's arguments filed 4/23/29 have been fully considered but they are not persuasive. Applicants argue that even accepting that the ACS reference may be used as evidence of an inherent property of hydroxyapatite, this does not establish that hydroxyapatite constitutes a calcium containing carrier mixture as recited in claim 1. The ACS reference establishes that hydroxyapatite is a calcium phosphate /hydroxide mineral, but does not establish that it functions as a carrier mixture for drug delivery. Applicants argue that the limitation “carrier” implies a functional role in carrying or delivering a therapeutic agent and the word “mixture” implies a composition for multiple components. Therefore, the ACS reference establishes only that hydroxyapatite contains calcium, it does not cure the deficiency in Murphy. The Applicants argue that the specification guidance on what constitutes a calcium containing carrier mixture, in the context of the claimed invention, hydroxyapatite alone does not fall within this definition. Applicants argue that the specification [0093],[0096] and [0119] establishes that the hydroxyapatite is combined with or incorporated into another calcium containing material. Applicants argue that the specification does not teach that hydroxyapatite alone constitutes a calcium containing carrier mixture. Applicants argue that hydroxyapatite is consistently described as an additive or seed material that is incorporated into calcium phosphate cements or other carrier compositions. Applicants further argue that Murphys hydroxyapatite particles are structural components or a porous scaffold matrix, not a carrier mixture for drug delivery. Applicants argue that Murphy does not teach a calcium phosphate cement or any other calcium containing composition that functions as a carrier for BMP-2. Applicants further argue that Murphy the BMP-2 is simply dripped onto the pre-formed scaffold prior to implantation, resulting in a drug applied to a scaffold.
These arguments were considered but are not persuasive. As evidenced by Noviyanti et al.(ASEAN Journal of Science and Engineering 4(2) (2024)191-206), HA is a delivery and carrier material (Abstract). Therefore, HA is well known in the art and shown in Noviyanti is a calcium containing carrier. With respect to the limitation “mixture”, Murphy et al. teaches CHA (collagen HA). Therefore, collagen and HA together meet the limitation of “mixture”. The specification does not specifically define “calcium containing carrier mixture” as CMC. The specification states “the carrier component of the drug carrier mixture may be any calcium containing mixture known in the art including calcium phosphate cements”. This does not limit the calcium containing carrier mixture to CMCs, but merely gives an example of one. If Applicants want to limit the calcium containing carrier mixture to CMC, the claims should be amended to recite that. The arguments that BMP-2 is simply a drug applied to a scaffold is not persuasive because the claims do not require a specific method of making the artificial periosteum. The resulting composition comprises BMP-2 and the calcium containing carrier mixture. The claim does not require mixing in BMP-2 at a specific time or manner. For the reasons presented above, the rejection is maintained.
The rejection of claims 1, 3-6 and 15-16 under 35 U.S.C. 103 as being unpatentable over Zheng et al. (US2014/0288271) and Murphy et al. (Acta Biomaterialia 10(2014) 2250-2258) as evidenced by Hydroxyapatite - American Chemical Society (accessed 1/16/26) in view of Tani et al. (“Doxorubicin-loaded calcium phosphate cement in the management of bone and soft tissue tumors” in vivo, 20; 55-60 (2006) previously presented).
The teachings of Zheng et al. and Murphy et al. are presented above in detail. The references do not teach an anti-cancer agent. However, the teachings of Tani et al. cure this deficiency.
Tani et al. the feasibility of adding anticancer drugs such as doxorubicin, which is widely used to treat malignant bone soft tissue tumors, to CPC to develop a new material which can release the drug, as well as fill the postoperative bony defects (p. 59, 1st col., 2nd to last para.). Tani et al. teach doxorubicin loaded calcium phosphate cement (CPC) markedly inhibited proliferation of sarcoma cells in a mouse model and the results indicate that doxorubicin loaded CPC may be useful in the local treatment of malignant bone and soft tissue tumors (Abstract). Tani et al. teach in the treatment of primary or secondary bone neoplasms, complete excision with reliable reconstruction is an essential procedure and the data showed that doxorubicin loaded CPC should be useful as a defect filling material.
With respect to claim 15, it would have been obvious to a person of ordinary skill in the art to include doxorubicin in the scaffold composition of Zheng et al. and Murphy et al. in order to locally treat and reconstruct bone and soft tissue tumors as taught by Tani et al. A person of ordinary skill in the art would look to the teachings of Tani et al. and have a motivation to include an anti-cancer agent in the composition of Zheng et al. and Murphy et al. in order to reconstruct bone after bone tumors because Murphy et al. teach the scaffold allows for improved delivery of multiple pharmaceutical or biological agents and Tani et al. teach that doxorubicin loaded CPC should be used as a defect filing material. There is a reasonable expectation of success given that multiple therapeutic agents are delivered in the scaffolds of Murphy et al.
Response to Arguments
Applicant's arguments filed 4/23/29 have been fully considered but they are not persuasive. Applicant argue that Tani does not cure the deficiencies of Zheng and Murphy. Applicants further argue that Tani and Murphy serve fundamentally different clinical purposes: Tani is directed to the local treatment of malignant bone and soft tissue tumors using anti-cancer drugs while Murphy is directed to bone tissue engineering and regeneration using anabolic and anti-catabolic agents to promote bone formation. Applicants argue that Tani’s own data demonstrates that doxorubicin loaded CPC actually inhibits bone formation. This is contrary to Murphys objective of promoting bone formation. Therefore, a person of ordinary skill in the art would not look to an anti-cancer drug delivery system which inhibits the very bone formation that Murphy seeks to promote. Applicant argue that Tani also does not teach a drug carrier mixture applied to a collagen membrane as claimed. The applicants argue that Tani’s CPC is used to fill bone defects as a standalone material that remains in gel for several minutes after power and solution have been mixed. Applicants argue this is not a drug carrier mixture.
This argument is not persuasive as Tani states that that doxorubicin loaded CPS should be useful as a defect filling material. Tani does states that bone formation was slower in doxorubicin CPC and concludes that bone formation permeating into CPC may occur at a later stage in doxorubicin loaded CPC. Therefore, a person of ordinary skill in the art would look to the teachings of Tani and have a motivation and reasonable expectation of success using doxorubicin. As indicated above, Zheng and Murphy make obvious the limitations of claim 1.
For the reasons presented above, the rejection is maintained.
Double Patenting-Maintained
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.
The rejection of Claims 1, 3-6 and 16 under 35 U.S.C. 103 as being unpatentable over U.S. Patent No. 10,314,939 in view of Murphy et al. (Acta Biomaterialia 10(2014) 2250-2258) as evidenced by Hydroxyapatite - American Chemical Society (accessed 1/16/26) is maintained.
The USPN claims a collagen containing membrane comprising greater than 80% type I collagen fibers, wherein the collagen-containing membrane has a first surface and a second surface that are distinct from each other with the first surface being a smooth surface having compact collagen bundles and the second surface being a rough, porous surface of loose collagen fibers (claim 1). The USPN teaches the membrane is between 50 µm and 200 µm thick. MPEP 804 states: those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application.
The USPN does not teach the collagen is a “functionalized collagen containing membrane or wherein the drug carrier mixture comprises BMP-2 and a calcium containing carrier mixture. However, the teachings of Murphy et al. cure this deficiency.
Murphy et al. teach collagen-hydroxyapatite (CHA) scaffold comprising BMP-2 and zoledronic acid (ZA) for bone formation (Abstract, Table 1). The CHA scaffold containing BMP-2 meets the limitation of “functionalized collagen-containing membrane” and “calcium containing mixture”. As evidenced by the American Chemical Society, hydroxyapatite, sometimes referred to as durapatite, is a calcium phosphate/hydroxide mineral that occurs naturally in “phosphate rock”. Please note that MPEP 2131.01 states: that an extra reference or evidence can be used to show an inherent characteristic of the thing taught by the primary reference. In the instant case, the reference is relied upon only to establish that hydroxyapatite is a calcium containing carrier mixture.
Murphy et al. teach that CHA demonstrates a capacity for both rhBMP-2 and bisphosphonates binding and delivery, which may make it superior for combination treatment compared to commercially available pure collagen scaffolds. Murphy et al. further teach that the CHA scaffolds demonstrate a capacity for mineralization in the absence of additional osteogenic factors and can be seen as a template for developing multicomponent scaffolds to allow for improved delivery of multiple pharmaceutical or biological agents (p. 2257, last para.).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to modify the scaffold of the USPN to include a drug carrier mixture and a calcium containing mixture as taught by Murphy et al. in order to achieve predictable bone growth effects associated with BMP-2 while retaining the advantageous membrane morphology and handling characteristics taught by the USPN. There is a reasonable expectation of success given that Murphy et al. demonstrates binding and controlled release of BMP-2 from collagen-hydroxyapatite systems.
With respect to the limitation “artificial periosteum” in the preamble, please note that MPEP 2111.02 II states "a preamble generally is not limiting when the claim body describes a structurally complete invention such that deletion of the preamble phrase does not affect the structure or steps of the claimed invention." In the instant case, the preamble does not affect the structure. The preamble in this case recites a statement of purpose or use, and therefore was not treated as a claim limitation. Furthermore, the claim body describes a structurally complete invention.
With respect to claims 3-4 and 6, zoledronic acid is a bone active agent that is a bisphosphonate. Murphy et al. teach osteoblast viability in the presence of Collagen, HA was protective (Fig.3). Murphy et al. teach that BMP-2 activates osteoblasts (Fig. 2).
With respect to claim 5, Murphy et al. teach decreased osteoclasts in the presence of ZA (Fig. 7). ZA meets the limitation of bone active agent that inhibits osteoclasts.
With respect to claim 16, the scaffold of Murphy et al. is a hydroxyapatite functionalized collagen membrane.
The rejection of claims 1, 3-6 and 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent No. 10,314,939 and Murphy et al. (Acta Biomaterialia 10(2014) 2250-2258) as evidenced by Hydroxyapatite - American Chemical Society (accessed 1/16/26) in view of Tani et al. (“Doxorubicin-loaded calcium phosphate cement in the management of bone and soft tissue tumors” in vivo, 20; 55-60 (2006) previously presented) is maintained.
The teachings of the USPN and Murphy et al. are presented above in detail. The references do not teach an anti-cancer agent. However, the teachings of Tani et al. cure this deficiency.
Tani et al. the feasibility of adding anticancer drugs such as doxorubicin, which is widely used to treat malignant bone soft tissue tumors, to CPC to develop a new material which can release the drug, as well as fill the postoperative bony defects (p. 59, 1st col., 2nd to last para.). Tani et al. teach doxorubicin loaded calcium phosphate cement (CPC) markedly inhibited proliferation of sarcoma cells in a mouse model and the results indicate that doxorubicin loaded CPC may be useful in the local treatment of malignant bone and soft tissue tumors (Abstract). Tani et al. teach in the treatment of primary or secondary bone neoplasms, complete excision with reliable reconstruction is an essential procedure and the data showed that doxorubicin loaded CPC should be useful as a defect filling material.
With respect to claim 15, it would have been obvious to a person of ordinary skill in the art to include doxorubicin in the scaffold composition of the USPN and Murphy et al. in order to locally treat and reconstruct bone and soft tissue tumors as taught by Tani et al. A person of ordinary skill in the art would look to the teachings of Tani et al. and have a motivation to include an anti-cancer agent in the composition of the USPN and Murphy et al. in order to reconstruct bone after bone tumors because Murphy et al. teach the scaffold allows for improved delivery of multiple pharmaceutical or biological agents and Tani et al. teach that doxorubicin loaded CPC should be used as a defect filing material. There is a reasonable expectation of success given that multiple therapeutic agents are delivered in the scaffolds of Murphy et al.
The rejection of claims 1, 3-6 and 16 under 35 U.S.C. 103 as being unpatentable over U.S. Patent No. 12,226,548 in view of Murphy et al. (Acta Biomaterialia 10(2014) 2250-2258) as evidenced by Hydroxyapatite - American Chemical Society (accessed 1/16/26) is maintained.
The USPN claims a collagen containing membrane comprising greater than 80% type I collagen fibers, wherein the collagen-containing membrane has a first surface and a second surface that are distinct from each other with the first surface being a smooth surface having compact collagen bundles and the second surface being a rough, porous surface of loose collagen fibers (claim 1). The USPN teaches the membrane is between 50 µm and 200 µm thick. MPEP 804 states: those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application.
The USPN does not teach the collagen is a “functionalized collagen containing membrane or wherein the drug carrier mixture comprises BMP-2 and a calcium containing carrier mixture. However, the teachings of Murphy et al. cure this deficiency.
Murphy et al. teach collagen-hydroxyapatite (CHA) scaffold comprising BMP-2 and zoledronic acid (ZA) for bone formation (Abstract, Table 1). The CHA scaffold containing BMP-2 meets the limitation of “functionalized collagen-containing membrane” and “calcium containing mixture”. As evidenced by the American Chemical Society, hydroxyapatite, sometimes referred to as durapatite, is a calcium phosphate/hydroxide mineral that occurs naturally in “phosphate rock”. Please note that MPEP 2131.01 states: that an extra reference or evidence can be used to show an inherent characteristic of the thing taught by the primary reference. In the instant case, the reference is relied upon only to establish that hydroxyapatite is a calcium containing carrier mixture.
Murphy et al. teach that CHA demonstrates a capacity for both rhBMP-2 and bisphosphonates binding and delivery, which may make it superior for combination treatment compared to commercially available pure collagen scaffolds. Murphy et al. further teach that the CHA scaffolds demonstrate a capacity for mineralization in the absence of additional osteogenic factors and can be seen as a template for developing multicomponent scaffolds to allow for improved delivery of multiple pharmaceutical or biological agents (p. 2257, last para.).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to modify the scaffold of the USPN to include a drug carrier mixture and a calcium containing mixture as taught by Murphy et al. in order to achieve predictable bone growth effects associated with BMP-2 while retaining the advantageous membrane morphology and handling characteristics taught by the USPN. There is a reasonable expectation of success given that Murphy et al. demonstrates binding and controlled release of BMP-2 from collagen-hydroxyapatite systems.
With respect to the limitation “artificial periosteum” in the preamble, please note that MPEP 2111.02 II states "a preamble generally is not limiting when the claim body describes a structurally complete invention such that deletion of the preamble phrase does not affect the structure or steps of the claimed invention." In the instant case, the preamble does not affect the structure. The preamble in this case recites a statement of purpose or use, and therefore was not treated as a claim limitation. Furthermore, the claim body describes a structurally complete invention.
With respect to claims 3-4 and 6, zoledronic acid is a bone active agent that is a bisphosphonate. Murphy et al. teach osteoblast viability in the presence of Collagen, HA was protective (Fig.3). Murphy et al. teach that BMP-2 activates osteoblasts (Fig. 2).
With respect to claim 5, Murphy et al. teach decreased osteoclasts in the presence of ZA (Fig. 7). ZA meets the limitation of bone active agent that inhibits osteoclasts.
With respect to claim 16, the scaffold of Murphy et al. is a hydroxyapatite functionalized collagen membrane.
The rejection of claims 1, 3-6 and 15-16 under 35 U.S.C. 103 as being unpatentable over U.S. Patent No. 12,226,548 and Murphy et al. (Acta Biomaterialia 10(2014) 2250-2258) as evidenced by Hydroxyapatite - American Chemical Society (accessed 1/16/26) in view of Tani et al. (“Doxorubicin-loaded calcium phosphate cement in the management of bone and soft tissue tumors” in vivo, 20; 55-60 (2006) previously presented) is maintained.
The teachings of the USPN and Murphy et al. are presented above in detail. The references do not teach an anti-cancer agent. However, the teachings of Tani et al. cure this deficiency.
Tani et al. the feasibility of adding anticancer drugs such as doxorubicin, which is widely used to treat malignant bone soft tissue tumors, to CPC to develop a new material which can release the drug, as well as fill the postoperative bony defects (p. 59, 1st col., 2nd to last para.). Tani et al. teach doxorubicin loaded calcium phosphate cement (CPC) markedly inhibited proliferation of sarcoma cells in a mouse model and the results indicate that doxorubicin loaded CPC may be useful in the local treatment of malignant bone and soft tissue tumors (Abstract). Tani et al. teach in the treatment of primary or secondary bone neoplasms, complete excision with reliable reconstruction is an essential procedure and the data showed that doxorubicin loaded CPC should be useful as a defect filling material.
With respect to claim 15, it would have been obvious to a person of ordinary skill in the art to include doxorubicin in the scaffold composition of the USPN and Murphy et al. in order to locally treat and reconstruct bone and soft tissue tumors as taught by Tani et al. A person of ordinary skill in the art would look to the teachings of Tani et al. and have a motivation to include an anti-cancer agent in the composition of the USPN and Murphy et al. in order to reconstruct bone after bone tumors because Murphy et al. teach the scaffold allows for improved delivery of multiple pharmaceutical or biological agents and Tani et al. teach that loxoribine loaded CPC should be used as a defect filing material. There is a reasonable expectation of success given that multiple therapeutic agents are delivered in the scaffolds of Murphy et al.
Response to Arguments
Applicant's arguments filed 4/23/26 have been fully considered but they are not persuasive. Applicants request this rejection be held in abeyance until allowable subject matter has been indicated.
This argument is not persuasive as no allowable subject matter has been indicated. The rejection is maintained.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TARA L MARTINEZ whose telephone number is (571)270-1470. The examiner can normally be reached Mon-Fri 8:00-5:00.
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/TARA L MARTINEZ/Primary Examiner, Art Unit 1654
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