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 .
DETAILED ACTION
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 3/10/2026 has been entered.
Claim Status
Claims 1-6, 9, 11 and 13-25 are pending. Claims 7-8, 10, 12 and 26-27 have been canceled. Claim 1 has been amended. Claims 1-6, 9, 11, 13-14 and 24-25 are being examined in this application. In the response to the restriction requirement, Applicants elected Invention I, poloxamer 407, recombinant amelogenin, trehalose (disaccharide), glycine (amino acid) and methionine (antioxidant). Claims 15-23 are withdrawn as being drawn to a nonelected species/invention.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
This is a new rejection.
Claims 1-6, 9, 11, 13-14 and 24-25 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 1 recites the broad recitation “a disaccharide…..an amino acid…..an antioxidant”, and the claim also recites “wherein said disaccharide is trehalose; said amino acid is glycine; and said antioxidant is methionine” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claims 2-6, 9, 11, 13-14 and 24-25, which depend from claim 1, are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as these claims incorporate by dependency the indefiniteness of claim 1.
Claim Rejections - 35 USC § 103
The rejection of claims 1, 5-6, 8-9 and 24-25 under 35 U.S.C. 103 as being unpatentable over Barthold et al. in view of Lyngstadaas et al. and Forney-Stevens et al. is withdrawn in view of the amendments to the claims.
The rejection of claims 1-6, 8-11 and 24-25 under 35 U.S.C. 103 as being unpatentable over Barthold et al. in view of Lyngstadaas et al., Forney-Stevens et al. and Bodratti et al. is withdrawn in view of the amendments to the claims.
The rejection of claims 1-6, 8-14 and 24-26 under 35 U.S.C. 103 as being unpatentable over Barthold et al. in view of Lyngstadaas et al., Forney-Stevens et al., Bodratti et al. and Sturesson et al. is withdrawn in view of the amendments to the claims.
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 is a new rejection.
Claims 1, 5-6, 9, 11 and 24-25 are rejected under 35 U.S.C. 103 as being unpatentable over Barthold et al. (WO 2011/051457) in view of Lyngstadaas et al. (WO 2006/064381), Pikal-Cleland et al. (Journal of Pharmaceutical Sciences, Vol. 91, NO. 9, September 2002) and Sturesson et al. (J Control Release. 2000 Jul 3;67(2-3):171-8).
Barthold et al. teach a pharmaceutical, dental and/or cosmetic composition, consisting of a suitable pharmaceutical carrier and purified Enamel Matrix Derivative (EMD) proteins (claim 1), and further teach that EMD comprises amelogenins (page 3, lines 7-10; passim), wherein the amelogenin is recombinant (page 16, lines 14-25).
Barthold et al. also teach that the composition comprises lactose or saccharose (page 26, lines 1-16), and an antioxidant such as ascorbic acid or cysteine (page 24, lines 15-16).
Barthold et al. further teach that “[a]n EMD protein according to the present invention can be incorporated into a polymeric matrix so that it is released by degradation of the polymeric matrix, by enzymatic action and/or by diffusion. Said polymeric matrix is either suitable for cellular in-growth, or cell-occlusive. Comprised in the invention is thus in particular a pharmaceutical, dental and/or cosmetic composition according to the present invention at a low total concentration within the formulation, wherein a spatial and/or selective regulation of release of said active enamel substance permits a great percentage of the active enamel substance to be released at the time of appropriate cellular activity. Polymeric matrices suitable for the purpose of the present invention are e.g. disclosed in WO 2006/064381” (page 25, lines 1-11; page 31, lines 5, 22 and 29).
Barthold et al. additionally teach that the EMD is lyophilized (page 29, lines 1-11).
Barthold et al. do not specifically teach that the disaccharide is trehalose; and that the composition comprises a poloxamer copolymer; and an amino acid selected from Ala, Gly, Ile, Leu, Pro, Val, and mixtures thereof.
Lyngstadaas et al. teach poly(ethylene oxide)-co-d(propylene oxide) block copolymers (i.e. a poloxamer copolymer) (para bridging pages 14-15).
Pikal-Cleland et al. teach that “[P]roteins are exposed to several stresses during freeze–thawing and the freezing step of lyophilization, as well as during storage of the frozen protein solution”, and further teach that “[P]revious studies have shown that glycine is one of many solutes that stabilize proteins via the preferential exclusion mechanism. Although this theory was originally defined for nonfrozen aqueous solutions, experimental evidence has demonstrated its validity for frozen systems as well” (page 1970, left column, 2nd para).
Sturesson et al. teach that “[I]n order to retain a high degree of bioactivity, the well-known protein stabilizers: sucrose, trehalose and poloxamer 407, were added to the urease in the preparation. The bioactivity of the entrapped urease was reduced more by methylene chloride than by ethyl acetate. The gelled form of poloxamer was shown to highly favor the retention of bioactivity, demonstrated by an increase of 41% compared to preparations without poloxamer. Moreover, the presence of poloxamer strongly increased the in vitro release rate of urease from the microspheres. The entrapment efficiency was increased by 44% using the sugars in the preparation. These results clearly show the great potential of small quantities of additive in the formulation to control the properties of the microspheres. The amount and type of additive could be adjusted according to the therapeutic application of the preparation” (abstract).
It would have been obvious to one of ordinary skill in the art to use the poloxamer copolymer of Lyngstadaas et al. in the invention of Barthold et al., because Barthold et al. teach that polymeric matrices suitable for the purpose of the present invention are disclosed in WO 2006/064381 (i.e. Lyngstadaas et al.).
The skilled artisan would have been motivated, with a reasonable expectation of success, to add glycine to the resulting composition because Pikal-Cleland et al. teach that glycine stabilizes proteins during freeze–thawing and the freezing step of lyophilization, as well as during storage of the frozen protein solution.
Furthermore, the MPEP 2144.06 states that it is obvious to substitute equivalents known for the same purpose.
Therefore, it would have been obvious to one of ordinary skill in the art to substitute the disaccharide of Barthold et al. with the disaccharide of Sturesson et al.
With respect to the claimed concentration of the various components, the MPEP 2144.05 A states that “[G]enerally, 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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997)”.
Since Applicant has not disclosed that the specific limitations recited in the instant claims are for any particular purpose or solve any stated problem, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum concentration of the various components, pH and viscosity by normal optimization procedures known in the pharmaceutical art.
With respect to claims 24-25, Barthold et al. teach that “[A] pharmaceutical, dental and/or cosmetic composition according to the present invention to be administered, may be adapted for administration by any suitable route, e.g. by systemic administration to a patient through a hose, syringe, spray or draining device (page 20, lines 28-30). Therefore, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to make a kit comprising the composition in a delivery mean such as a syringe.
This is a new rejection.
Claims 1-6, 9, 11, 13-14 and 24-25 are rejected under 35 U.S.C. 103 as being unpatentable over Barthold et al. (WO 2011/051457) in view of Lyngstadaas et al. (WO 2006/064381), Pikal-Cleland et al. (Journal of Pharmaceutical Sciences, Vol. 91, NO. 9, September 2002) and Sturesson et al. (J Control Release. 2000 Jul 3;67(2-3):171-8) as applied to claims 1, 5-6, 9, 11 and 24-25 above, and further in view of Bodratti et al. (J Funct Biomater. 2018 Jan 18;9(1):11).
The teachings of Barthold et al., Lyngstadaas et al., Pikal-Cleland et al. and Sturesson et al. with respect to claims 1, 5-6, 9, 11 and 24-25 have been discussed above.
Barthold et al., Lyngstadaas et al., Pikal-Cleland et al. and Sturesson et al. do not teach the poloxamer is poloxamer 407.
Bodratti et al. teach that “[P]oloxamer 407 is widely used because it can form hydrogels at lower block copolymer concentrations in water” (page 5, 2nd para).
The MPEP 2144.06 states that it is obvious to substitute equivalents known for the same purpose.
In the instant case, it would have been obvious to one of ordinary skill in the art to substitute the poloxamer of Lyngstadaas et al. for the poloxamer of Bodratti et al.
With respect to claims 4 and 13-14, the MPEP 2144.05 A states that “[G]enerally, 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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997)”.
Since Applicant has not disclosed that the specific limitations recited in the instant claims are for any particular purpose or solve any stated problem, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum concentration of the poloxamer 407, the disaccharide, the amino acid, and the antioxidant, by normal optimization procedures known in the pharmaceutical art.
Response to Arguments
Applicant’s arguments filed on 3/10/2026 have been fully considered but they are not persuasive.
Applicant argues that, as shown in Table 2, “[s]tandard stabilizer sugar such as trehalose alone (PX26-14) failed to stabilize amelogenin in the poloxamer environment. In contrast, both compositions including trehalose as disaccharide, methionine as antioxidant and glycine as amino acid (PX26-15-2 and PX26-16) provided high stability even after 12 months of storage. However, adding methionine as antioxidant without the amino acid glycine (PX26-18) failed to achieve high stability. Thus, it can be seen that not any combination of ingredients can have an expectation of producing stability in the claimed thermosensitive formulation”.
Applicant’s arguments are not persuasive because, as discussed in the rejection above, Pikal-Cleland et al. teach that glycine stabilizes proteins during freeze–thawing and the freezing step of lyophilization, as well as during storage of the frozen protein solution.
Therefore, one of ordinary skill in the art would have expected the addition of glycine to stabilize the claimed recombinant amelogenin during the freezing step of lyophilization, as well as during storage.
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/SERGIO COFFA Ph.D./
Primary Examiner
Art Unit 1658
/SERGIO COFFA/Primary Examiner, Art Unit 1658
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