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 .
Claim Status
Claims 9-12 and 39-42 are pending.
Claims 9-10 and 39-40 are currently amended.
Claims 1-8, 13-38, and 43-61 are cancelled.
Claims 9-12 and 39-42 have been examined.
Priority
This application is a 371 of PCT/US2017/043614 07/25/2017
PCT/US2017/043614 has PRO of 62366370 07/25/2016
Withdrawn Rejection
All rejections of record are withdrawn because more relevant references are found and used for the new ground of rejection in the following.
New Ground of Rejection
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
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.
Claims 9-12 and 39-42 are rejected under 35 U.S.C. 103 as being unpatentable over Qian et al. (J Biomed Mater Res. 1996 Aug;31(4):545-54, previously cited 7/29/2022) in view of Reves et al. (J Biomed Mater Res Part B: Appl Biomater 90B: 1–10, 2009) and Buschmann et al. (AU 2001268882 B2)
Claim 9 is drawn to a method for coating calcium phosphate particles with a peptide of SEQ ID NO: 1 comprising the steps of:
Add calcium phosphate particles without the peptide to a first aqueous salt solution having an osmolarity value of between 400 and 1,200 mOsm and a pH of between 6.5 and 8.5, followed by drying the calcium phosphate particles to produce dried pretreated calcium phosphate particles;
Combine the dried calcium phosphate particles with a second aqueous salt solution containing the peptide and having an osmolarity value of between 400 and 1,200 mOsm and a pH of between 6.5 and 8.5 to produce coated calcium phosphate particles;
separating the peptide coated calcium phosphate particles from the second aqueous salt solution; and
wherein the peptide binding to the pretreated particles is increased in comparison to peptide binding to calcium phosphate particles that are not pretreated with buffered saline solution
Qian et al. teach “Enhanced cell attachment to anorganic bone mineral in the presence of a synthetic peptide related to collagen” (Title). Qian et al. teach the anorganic bone mineral is pure hydroxyapatite (p546, col 1, Anorganic bone mineral), reading on calcium phosphate particles. Qian et al. teach the coated peptide consisting of GTPGPQGIAGQRGW, P-15, (p545, col 2, Peptide synthesis) with 100% identity to the elected species of SEQ ID NO: 1. Qian et al. teach the peptide coating process comprising incubation of the peptide with calcium phosphate particles (hydroxyapatite) in phosphate-buffered saline (p546, col 1, Preparation of AMP.P15).
Qian et al. do not specify a pretreatment of drying calcium phosphate particles (hydroxyapatite) to increase peptide binding to calcium phosphate particles.
Reves et al. teach taking advantage of the increased porosity due to lyophilization to increase the loading capacity of a composite comprising calcium phosphate (Abstract). Reves et al. teach the calcium phosphate is hydroxyapatite (p2, Fabrication of Composite Microspheres and Scaffolds, para 1). Reves et al. teach lyophilization or freeze-drying has been used to
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increase the porosity of biomaterials and increase the loading capacity for therapeutic agents known in the art (p2, col 1, last para). Reves et al. show lyophilization able to increase the porosity of hydroxyapatite composition as expected (p4, Fig 2; see Fig 2(A) compared
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to 2(B)) and the surface area also increases significantly shown as follows (p5, Table I). Reves et al. further teach lyophilization increased protein ALP- and BMP-2-loading capacity likely due to the expanded surface area brought about by roughened surface texture and additional porosity capacity of the microspheres (p8, col 1, para 2). Reves et al. further teach the use of calcium phosphates have been used for implant coatings known in the art (p2, col 1, para 3) for bone repair (p2, col 1, para 1-2). Reves et al. further suggest lyophilization of a composition comprising hydroxyapatite for cell attachment (p8, Table III). Because Reves et al. teach advantages of freeze drying comprising (a) increase the porosity of a hydroxyapatite composition (p4, Fig 2) and surface area (p5, Table I), (b) increase loading capacity of proteins (p8, col 1, para 2), and (c) suitable for cell attachment (p8, Table III), one of ordinary skill in the art would have found it obvious to beneficially dry the calcium phosphate particles before coating a peptide to increase porosity and surface area of hydroxyapatite (calcium phosphate particles) in order to increase loading capacity of Qian’s P-15 peptide.
Qian et al. teach coating the P-15 peptide to hydroxyapatite in a phosphate-buffered saline (p546, col 1, last para) and used on implant surfaces (p548, col 1, para 1), but did not specify pH and osmolarity value.
Buschmann et al. teach optimization of a tissue-repair composition (e.g., medical implant See p23, line 11-18, Fig 9-11) in a buffer to maintain pH between 6.5 and 7.8 and an physiological value of osmolarity between 250 mOsm and 600 mOsm (p20, line 1-12). Buschmann et al. the tissue-repair composition can be used for bone repair (p1, line 5-9, claim 26). Because Buschmann et al. teach pH between 6.5 and 7.8 and an physiological value of osmolarity between 250 mOsm and 600 mOsm is suitable for making an implant for bone repair, one of ordinary skill in the art would have found it obvious to use the salt solution of phosphate-buffered saline solution to maintain pH between 6.5 and 7.8 and an physiological value of osmolarity between 250 mOsm and 600 mOsm for (i) making a pretreated dried hydroxyapatite before coating Qian’s peptide P-15 to increase loading capacity of the peptide and (ii) perform coating Qian’s peptide P-15 in substantially the same salt solution to generate a P-15 peptide coated hydroxyapatite, which is expected to have increased loading capacity of P-15 peptide with pretreatment of drying hydroxyapatite compared to a P-15 peptide coated hydroxyapatite without drying.
With respect to step (i) Reves et al. teach lyophilization or freeze-drying has been used to increase the porosity of biomaterials and increase the loading capacity for therapeutic agents known in the art (p2, col 1, last para). Reves et al. show lyophilization able to increase the porosity of hydroxyapatite composition (p4, Fig 2), surface area (p5, Table I), and loading capacity of protein/polypeptide (p8, col 1, para 2). Thus, one of ordinary skill in the art is taught to pretreat hydroxyapatite with lyophilization or freeze drying. Furthermore, Buschmann et al. teach optimization of a tissue-repair composition (e.g., medical implant See p23, line 11-18, Fig 9-11) in a buffer to maintain pH between 6.5 and 7.8 and an physiological value of osmolarity between 250 mOsm and 600 mOsm (p20, line 1-12). Buschmann et al. teach the tissue-repair composition can be used for bone repair (p1, line 5-9, claim 26). Therefore, one of ordinary skill in the art is taught to prepare an implant for bone repair in a buffered salt solution at pH 6.5~7.8 with an physiological value of osmolarity between 250 mOsm and 600 mOsm for lyophilization of hydroxyapatite to produce dried pretreated calcium phosphate particles with a peptide.
With respect to step (ii), Qian et al. teach the peptide coating process comprising incubation of the peptide with calcium phosphate particles (hydroxyapatite) in phosphate-buffered saline (p546, col 1, Preparation of AMP.P15). One of ordinary skill in the art would have found it obvious to performing peptide coating in either the same or substantially the same condition at pH 6.5~7.8 with an physiological value of osmolarity between 250 mOsm and 600 mOsm to generate a composition suitable for implant of bone repair.
With respect to step (iii), Qian et al. teach the unbound peptide was washed away (p546, col 1, last para). Qian et al. teach the coated peptide consisting of GTPGPQGIAGQRGW, P-15, (p545, col 2, Peptide synthesis) with 100% identity to the elected species of SEQ ID NO: 1.
With respect to the wherein clause (iv), Reves et al. teach proteins or drugs incorporated into the pretreatment of freeze-dried composition comprising hydroxyapatite are not lost during the wash step compared to 90% therapeutic agent lost from the composition without pretreatment of freeze-drying (p8, col 2, para 1), reading on the wherein clause.
Thus, Qian et al. in view of Reves et al. and Buschmann et al. is obvious to the instant claim 9.
One or ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine (i) Qian et al. and (ii) Reves et al. because (a) Qian et al. a process of coating a peptide to a calcium phosphate particle of hydroxyapatite and (b) Reves et al. teach lyophilization or freeze-drying has been used to increase the porosity of biomaterials and increase the loading capacity for therapeutic agents known in the art (p2, col 1, last para). Reves et al. further teach proteins or drugs incorporated into the pretreatment of freeze-dried composition comprising hydroxyapatite are not lost during the wash step compared to 90% therapeutic agent lost from the composition without pretreatment of freeze-drying (p8, col 2, para 1). The combination would have reasonable expectation of success because both references teach a composition comprising hydroxyapatite loading with a protein/polypeptide.
One or ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine (i) Qian et al. in view of Reves et al. with (ii) Buschmann et al. because (a) Qian et al. teach the use of a peptide coated hydroxyapatite as an implant for bone repair (p545, col 2, 4th last line; p548, col 1, 2nd line) and (b) Buschmann et al. teach optimization of a tissue-repair composition (e.g., medical implant See p23, line 11-18, Fig 9-11) in a buffer to maintain pH between 6.5 and 7.8 and a physiological value of osmolarity between 250 mOsm and 600 mOsm (p20, line 1-12) used for bone repair (p1, line 5-9, claim 26). The combination would have reasonable expectation of success because all references teach an implant for bone repair.
With respect to claims 10 and 39-40, the limitations are substantially the same as claim 9 except for a limitation of “at least two hours” for coating peptide to the pretreated calcium phosphate particles and the other limitation of drying process as freeze followed by drying.
The reaction time for coating Qian’s P-15 peptide to calcium phosphate particles (hydroxyapatite) is a result effective variable can be determined by routine experimentation depending on the concentration of the peptide. Thus, one of ordinary skill in the art would optimize the coating time such as 2 hours, 3 hours, 5 hours, or 24 hours by routine experimentation. For example, Qian et al. teach the coating step comprising incubation of ABM/hydroxyapatite (calcium phosphate particle) with the peptide of P-15 in a coating solution for 24 hours (p546, col 1, Preparation of ABM.P-15). Reves’s teaching of lyophilization is the same of freeze-drying known to freezing followed by drying as claimed.
With respect to claims 11 and 41, Qian et al. teach the buffer is a phosphate buffered saline (p546, col 1, last para). Buschmann et al. teach buffers are selected from glucose phosphate (reading on phosphate buffer), HEPES, or PIPES (p20, line 5-9).
With respect to claims 12 and 42, Buschmann et al. suggest a bone implant composition is preferably initially dissolved or suspended in a buffer containing inorganic salts such as sodium chloride (p20, line 1-3). Buschmann et al. teach optimization of a tissue-repair composition (e.g., medical implant See p23, line 11-18, Fig 9-11) in a buffer to maintain pH between 6.5 and 7.8 and a physiological value of osmolarity between 250 mOsm and 600 mOsm (p20, line 1-12). For osmolarity of 600 mOsm of sodium chloride solution, the concentration of sodium chloride is 300 mM.
Response to Arguments
Applicant's arguments filed on 3/25/2026 have been fully considered but they are not persuasive because the arguments are not applied to the new ground of rejection based on Qian et al. in view of Reves et al. and Buschmann et al.
New ground of Rejection
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 9-12 and 39-42 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, and 16 of U.S. Patent No. 9,415,139 B2 (the ‘139 patent) in view of Wu et al., Bohner et al., Benedict et al., Barbosa-Canovas, Natan et al., Behnam, Will et al. and Qian et al.
Claims 1 and 5 of the ‘139 patent disclosed hydroxyapatite particles (calcium phosphate particles) coated with P-15 peptide.
Claim 16 of the ‘139 patent disclosed P-15 peptide sequence of SEQ ID NO: 1.
Claims 1, 5, and 16 of the ‘139 patent do not explicitly teach a method of making P-15 coated hydroxyapatite particles (calcium phosphate particles).
The relevancy of Qian et al., Reves et al. and Buschmann et al. as applied to claims 9-12 and 39-42 above not repeated here.
Because of Qian et al., Reves et al. and Buschmann et al. teach beneficially coating of the P-15 peptide taught by claims 1, 5, and 16 of the ‘139 patent to a calcium phosphate as an implant to treat bone disease, one of ordinary skill in the art would have found it obvious to combine claims 1, 5, and 16 of the ‘139 patent with Qian et al. in view of Reves et al. and Buschmann et al.
Thus, claims 1, 5, and 16 of the ‘139 patent in view of Qian et al., Reves et al. and Buschmann et al. are obvious to the instant claims 9-12 and 39-42.
Response to Arguments
Applicant's arguments filed on 3/25/2026 have been fully considered but they are not persuasive because the arguments are not applied to the new ground of rejection above.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/J.L/Examiner, Art Unit 1658
27-May-2026
/Melissa L Fisher/ Supervisory Patent Examiner, Art Unit 1658
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