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 .
Claims and Previous Objections/Rejections Status
Claims 1-9 are pending in the application.
Any objections and/or rejections from previous office actions that have not been reiterated in this office action are obviated.
Modified Grounds of Rejection Necessitated by the Amendment
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.
Claim(s) 1-9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pedrozo et al. (WO 2009/108934A2) in view of Wenz (WO2004/050131A1) and Thakur et al. (US 2015/0344882A1) and in
further view of McKay et al. (US 2014/0341964A1) and Genin et al. (US 2003/0055512A1) as stated in the office action mailed 11/10/25 but the reference of Pedrozo et al. is modified to address the amendment to the claims.
Pedrozo et al. (WO 2009/108934A2) discloses an injectable calcium phosphate cement/paste formulated with bioactive agents (title; abstract; p4, lines 4-7 and 31-32; p31, lines 26-31).
The injectable calcium phosphate cement bone substitute composition comprises a paste that is made by a process of combining a solid phase and a liquid phase (p5, lines 22-26; p lines 14-17).
The solid phase comprises calcium phosphate cement particles, at least one porogen, excipients, additives, etc. (p4, lines 8-11 and 20-21; p5, lines 18-21 and 23-25).
The calcium phosphate cement particles comprise tricalcium phosphate, hydroxyapatite, etc. (p11, lines 14-24; p16, lines 12-17) that encompasses the biphasic calcium phosphate particles, tricalcium phosphate (TCP) and hydroxyapatite (HA), respectively of the instant claims 2 and 3.
The porogen comprises one or more biodegradable and/or bioresorbable composition, such as collagen (p4, lines 8-17; p7, lines 30+; p8, lines 1-4, especially line 4) that encompasses the powdered collagen of the instant claims.
The excipients comprise sodium phosphate (p5, lines 20-21).
The additives comprise disodium hydrogen phosphate (Na2HPO4), sodium dihydrogen phosphate (NaH2PO4), etc. (p11, lines 26+, especially line 28) that encompass the curing agents of the instant claim 8.
The liquid phase comprises a physiologically acceptable aqueous phosphate setting solution (p41, lines 17-20; p5, lines 18-20) that encompasses the diluted saline solution of the instant claims.
The setting solution/liquid is a liquid composition that, when contacted with the calcium phosphate cement particles, allow cementing reactions to occur. The setting solution/liquid comprises suitable acids, such as citric acid, acetic acid and their mixtures (p12, lines 1-11) that encompasses the
acidifying agents citric acid and acetic acid of the instant claim 7.
The injectable calcium phosphate cement (CPC) comprises an osteoinductive composition that may be provided as a component of the liquid phase (p4, lines 4-7; p5, lines 26-27; p43, lines 19-20).
The osteoinductive composition includes one or more bioactive agents/osteogenic agents comprising naltrexone, etc. (p4, lines 31-32; p30, lines 7-28, especially line 27) that encompasses the naltrexone OGFR antagonist of the instant claim 6.
The osteoinductive composition comprising one or more bioactive agents/osteogenic agents that may be provided as a component of the liquid phase encompasses the OGFR antagonist is included in the liquid solution of the instant claims.
The inclusion of biodegradable/bioresorbable porogens advantageously result in a matrix that locally releases the bioactive composition for the hardened cement over time, thereby delivering a therapeutic dose of the bioactive composition (p6, lines 6-8; p41, lines 28-31).
The cumulative release of components of bioactive composition is approximately 24 hours after introduction (p6, lines 21-23; p9, lines 4-8).
The bioactive agents are gradually released from the crystalline calcium phosphate layer in a sustained manner (p31, lines 31+; p38, lines 30+) that encompasses the release of OGFR antagonist in a controlled rate of the instant claim 5.
The references of Wenz (WO2004/050131A1), Thakur et al. (US 2015/0344882A1), McKay et al. (US 2014/0341964A1) and Genin et al. (US 2003/0055512A1) are as stated in the rejection mailed 11/10/25.
Response to Arguments
Applicant's arguments filed 1/29/26 have been fully considered but they are not persuasive.
Applicant asserts that Pedrozo discloses two main types of compositions, one being a previously hardened implantable product and the other being a cement (e.g. stating that “[t]he ratio of the solid
phase to the liquid phase of the composition may be sufficient to form a paste that can readily be injected using syringe to a site on a bone or to a mod in order to make an implantable structure”). Only cement is a moldable composition. The action cited Pedrozo’s teaching of phosphate buffered saline. As shown on p 48 of Pedrozo, this treatment of the already solidified implant with PBS achieves a specific surface effect on the implant. Because Pedrozo only teaches use of saline with the “dried material made in Example 1”, which is a solidified implant, there is no motivation based on Pedrozo to use saline for a moldable composition.
The reference of Pedrozo teaches that the injectable calcium phosphate cement bone substitute composition comprises a paste that is made by a process of combining a solid phase and a liquid phase.
The liquid phase for the moldable paste comprises a physiologically acceptable aqueous phosphate setting solution and therefore, does teach of an aqueous saline solution.
Applicant asserts that McKay, to the extent it includes an osteogenic agent (collagen), is focused on bone morphogenic proteins, not OGFR antagonists derived from oxymorphone as presently claimed. A person of ordinary skill in the art combining McKay with Pedrozo would be motivated to use BMP rather than an OGFR antagonist derived from oxymorphone.
The reference of McKay et al. was not explicitly used to teach of the collagen or OGFR antagonists derived from oxymorphone.
The reference of McKay et al. was used to teach that malleable, shape-retaining putty to treat bone and provide a scaffold for bone growth comprising biphasic calcium phosphate with tricalcium phosphate:hydroxyapatite in a ratio of about 50:50 to about 95:5, about 70:30 to about 95:5, or about 80:20 to about 90:10.
The reference of Genin et al. was used to teach of a moldable putty bone substitute comprising calcium sulfate, hydroxyapatite and/or calcium phosphates wherein the addition of hydroxyapatite and beta-tricalcium phosphate to calcium sulfate will slow down the resorption process and will help
support bone regeneration at the site for a longer period of time.
It would have been obvious to one of ordinary skill in the art before the effective filing date of
the claimed invention to vary the tricalcium phosphate:hydroxyapatite ratio to about 50:50 or about 80:20 for the advantage of changing the resorption rate, such as slow down the resorption process to help support bone regeneration at the site of treatment for a longer period of time.
Applicant asserts that Thakur does not teach or suggest incorporating iron (III) sulfate into the composition, or the particular combination of ingredients recited in claim 1.
The reference of Thakur was not used to teach of iron (III) sulfate but was used to teach of tricalcium phosphate bone matrix paste compositions for promoting bone formation comprising the OGFR antagonists naloxone, naltrexone, etc.
It would have been obvious to one of ordinary skill in the art before the effective filing date of
the claimed invention to substitute the naltrexone OGFR antagonist in the calcium phosphate cement/paste of Pedrozo et al. for the analogous OGFR antagonist naloxone of Thakur et al. to predictably provide the advantage of delivery of a bioactive agent for therapeutic applications with a reasonable expectation of success.
Applicant asserts that the phrase “iron sulfate” nowhere appears in Wenz. The closest Wenz comes to disclosing iron sulfate are two passages (see Remarks) that both teach away from iron sulfate. The passage would require many choices to be made before reaching iron sulfate as a selection from a list so large that it would be akin to selecting a needle in a haystack. First, a person of ordinary skill in the art would have to ignore paragraph [0009], which teach a preference for metal oxides. Next, from paragraph [0020], one would have to select metal sulfate from the list of “metal oxides, metal nitrides, metal carbides, metal silicas, metal halides, metal phosphates, metal gluconates, metal citrates, metal fumarates and metal sulfates and metal-organic compounds.”
The reference of Wenz was used to teach of tricalcium phosphate bone substitute cement/paste
compositions comprising a radiopaque material to enhance X-ray contrast.
Wenz explicitly states that the iron compounds include oxides, sulfates or phosphates which is a finite list of iron radiopaque materials. The radiopaque material is selected depending on the purpose and the intended use.
Applicant asserts that evidence of unexpected results presented in the present specification more than rebuts any possible case of obviousness. First, the particular ingredients recited in claim 1 are unexpectedly successful when a small molecule active agent is used, such as an OGFR antagonist derived from oxymorphone:
The chemical properties of the powder-dry slurry component of a bone graft can be designed so that when the powder-dry slurry component is mixed with a diluent, the small molecule active agent becomes less soluble and becomes sequestered in the material. Further, this property can be used to control elution and bioavailability of a small molecule active agent.
Second, the inclusion of iron (III) sulfate unexpectedly increases the osteogenic capacity of the composition. As shown by the comparative results presented in Fig. 1, “[t]he iron (III) sulfate bone graft cultures had significantly more mineral in the spheroids (*= p<0.0001) versus the negative control cultures. The cited references nowhere suggest that iron (III) sulfate would increase bone growth as demonstrated by the comparative tests in the present specification.
The reference of Pedrozo teaches of the inclusion of biodegradable/bioresorbable porogens that advantageously result in a matrix that locally releases the bioactive composition for the hardened cement over time, thereby delivering a therapeutic dose of the bioactive composition after mixing the solid phase with the liquid phase and therefore, it would not have been unexpected that the composition provides sequestration of the bioactive agent, controlled elution and bioavailability of the bioactive agent.
The calcium phosphate ceramics comprising TCP and HA of Pedrozo promote bone ingrowth and therefore, the increase in bone growth is not unexpected.
Also, the reference of Pedrozo teaches that the bioactive agents, such as collagen supports the
formation, development and growth of new bone and therefore, the increase in bone growth is not
unexpected.
The reference of Wenz teaches of tricalcium phosphate bone substitute cement/paste compositions comprising a radiopaque material to enhance X-ray contrast, such as iron sulfate as well as that stated above.
The iron sulfate of Wenz encompasses the iron sulfate of the instant claims, has the same properties and is capable of the same functions, such as increase bone growth.
The statement of increased osteogenic capacity and increased bone growth are subjective statements that do not provide any quantitative data.
The arguments of counsel cannot take the place of evidence in the record. Examples of attorney statements are not evidence and must be supported by an appropriate affidavit or declaration include statements regarding unexpected results. MPEP § 716.01 (c).
Response to Arguments
Applicant's arguments filed 1/29/26 have been fully considered but they 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 1-9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 and 13 of U.S. Patent No. 12,390,551B2 as stated in the office action mailed 11/10/25.
Applicant asserts that they will address any rejections that remain following the amendment to the claims.
The rejection is maintained.
The rejection over copending Application No. 17/143,468 in view of Thakur et al. (US 2015/0344882A1) is withdrawn due to the abandonment of Application No. 17/143,468.
Conclusion
No claims are allowed at this time.
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 MELISSA JEAN PERREIRA whose telephone number is (571)272-1354. The examiner can normally be reached M9-3, T9-3, W9-3, Th9-2, F9-2.
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/MELISSA J PERREIRA/ Examiner, Art Unit 1618
/Michael G. Hartley/ Supervisory Patent Examiner, Art Unit 1618