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 1-22 are cancelled.
Claims 23-43 are presented for examination on the merits.
Priority
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Information Disclosure Statement
The information disclosure statement (IDS) submitted on 7/15/24 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 23-25, 27-35 and 37-43 are rejected under 35 U.S.C. 103 as being unpatentable over Gurtner et al. (WO2011109129; of record) and Zazzatta (WO2013053457; of record) and Molliard (US 20150257989; of record).
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103, the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103.
Applicant claims, for example:
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Level of Ordinary Skill in the Art
(MPEP 2141.03)
MPEP 2141.03 (I) states: “The “hypothetical ‘person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988). The level of skill is that of a cosmetic medicine research scientist, as is the case here, then one can assume comfortably that such an educated artisan will draw conventional ideas from cosmetic medicine technology, such as construction of hyaluronic threads for use in aesthetic applications, and conventional synthetic techniques to construct hyaluronic based threads— without being told to do so.
In addition, the prior art itself reflects an appropriate level (MPEP 2141.03(II)).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Regarding claims 23, 27, 31, 33, 37, 41 and 43, Gurtner et al. teach methods of making a thread comprising hyaluronic acid threads comprising hyaluronic acid wherein at least a portion of the hyaluronic acid is interlocked and further wherein at least a portion of the hyaluronic acid is cross-linked, said method comprising drying under ambient conditions an aqueous gel composition comprising hyaluronic acid and a cross-linking agent to provide a dried thread (claims 17-38; page 29, lines 1-31). Accordingly, prior to forming a wet thread, Gurtner et al. provide a thread precursor composition. Gurtner et al. teach employing from about 1% to about 30% by weight of hyaluronic acid in the aqueous solution (Claim 25), which overlaps the claimed range of between 0.2 and 8 weight percent. The thread is extruded through a syringe, which has an orifice, onto a substrate, which naturally has a surface, and is wet prior to drying (Claim 40; [0073]). Gurtner et al. teach wherein the composition is provided by adding the cross-linking agent to an aqueous solution comprising hyaluronic acid (Claim 24) with about 0.1 to about 5.0% by volume of crosslinking agent (Claim 28) and where the hyaluronic acid is crosslinked with BDDE (claims 4-5). It is implicit in the process of Gurtner et al. that the reaction mixture is allowed to commence cross-linking and allowed to complete the cross-linking reaction (See for example page 29, step 3). Gurtner et al. teach that the process further comprising a biodegradation impeding agent (claims 16 and 39) where the term "biodegradation impeding agent" is intended to refer to a biocompatible substance that slows or prevents the in vivo degradation of the thread [0054].
Regarding claims 23-24, 33-34 and 43, Gurtner et al. teach adjusting the pH of the solution with a sodium carbonate or sodium hydroxide (Claims 22-23; [0070-0071]), hence buffering agents, to bring the pH value to an essentially neutral value of about pH 7 (Claim 19), thus neutralizing the aqueous medium.
Regarding claims 25 and 35, Gurtner et al. teach BDDE (1,4-butanediol diglycidyl ether) for the crosslinking agent [0017, 0045].
Regarding claims 32 and 42, Gurtner et al. teach sterilizing the thread [0081, 0142, 0154].
Regarding claim 33, as shown in Figure 1A example D, the diameter of the thread is essentially uniform where the variation of the diameter expressed as relative standard deviation of diameter of SEM measurements taken along the length of the thread appears being less than 20%.
Regarding claim 43, Gurtner et al. teach drying the wetted thread to less than about 30% or less than about 15% hydration (Page 29, lines 22-26).
Gurtner et al. also teach that: “This tissue repair could prolong the "filler" effects of the thread when used to treat or fill a wrinkle or provide facial contouring in vivo far beyond the half-life of the hyaluronic acid-based thread.” [0008] See also [0011, 0020, 0022, 0092-97]; Figures 5 and 7; claim 49).
Regarding claims 23-25, 33-35 and 43, Zazzatta teaches a process comprising:
Mixing hyaluronic acid and hydroxyapatite with a solution of BDDE (1,4-butanediol diglycidyl ether), NaOH1 and water, where addition of NaOH implicitly increases the pH of the medium;
Adding hydrochloric acid2 to stop the reaction, thus neutralizing the aqueous medium;
To produce a biphasic gel of crosslinked hyaluronic acid containing hydroxyapatite (page 7, lines 1-7; claims 4-5), which reads on providing an extrudable thread precursor composition.
Regarding claims 27 and 37, Zazzatta teach that the concentration of hyaluronic acid is between 1-4% (page 8, lines 10-11) which falls within the claimed range of between 0.2-8 wt% in the aqueous medium because Zazzatta’s product is an aqueous gel. See MPEP 2144.05(I): In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976).
Zazzatta also teaches that one function of the hydroxyapatite is to extend the time it stays in the tissues (page 8, lines 16-19; claim 2), thus impeding biodegradation and the amount of hydroxyapatite used would be a result effective variable to vary the rate of biodegradation. Zazzatta also teaches that the gel is used for filling wrinkles and restoring volume to the face and bone or as a bone tissue substitute as known in cosmetic medicine (Abstract; page 1, lines 7-10 and 19-21; page 9, lines 15-26; claim 1).
Regarding claims 28-30 and 38-40, Molliard teaches adding calcium hydroxyapatite particles of 30-50 microns after making the hyaluronic gel [0053, 0066, 0068], where the injectable formulation can have between 1-4% mass/vol crosslinked hyaluronic acid and between 5-60% mass/vol hydroxyapatite with an average particle size of less than 200 microns (claims 18 and 37) for filling and or restoring volumes of biological tissue (claim 34) such as wrinkles [0007].
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02) and Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
The difference between the instant application and Gurtner et al. is that Gurtner et al. do not expressly teach using calcium hydroxyapatite wherein a concentration of calcium hydroxyapatite in said aqueous medium is between 0.5 and 5 weight percent or between 5 and 20 weight percent and an average particle size distribution between 25 and 45 microns. This deficiency in Gurtner et al. is cured by the teachings of Zazzatta and Molliard. It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to make the hyaluronic acid thread Gurtner et al. with calcium hydroxyapatite wherein a concentration of calcium hydroxyapatite in said aqueous medium is between 0.5 and 5 weight percent or between 5 and 20 weight percent and an average particle size distribution between 25 and 45 microns, as suggested by Zazzatta and Molliard, and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because Gurtner et al. suggest adding a biodegradation impeding agent and Zazzatta and Molliard guide the artisan to using calcium hydroxyapatite where Zazzatta teaches that one function of the hydroxyapatite is to extend the time it stays in the tissues (page 8, lines 16-19; claim 2), thus impeding biodegradation. Furthermore, Molliard provides guidance for the artisan to employ between 5-60% mass/vol hydroxyapatite with an average particle size of less than 200 microns, which overlaps the claimed range. Consequently, it is merely routine optimization to employ a concentration of calcium hydroxyapatite in said aqueous medium is between 0.5 and 5 weight percent or between 5 and 20 weight percent and an average particle size distribution between 25 and 45 microns. See MPEP 2144.05 (II) (A): “[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).
The difference between the instant application and Gurtner et al. is that Gurtner et al. do not expressly teach forming an alkaline mixture of hyaluronic acid and cross-linking agent and allow to commence cross-linking and then adding calcium hydroxyapatite before neutralizing the aqueous medium by adding a buffering agent to bring the pH value to an essentially neutral value. However, employing calcium hydroxyapatite is obvious as asserted above and Zazzatta provide further guidance on the adjusting the pH of the reaction mixture with NaOH and neutralizing said reaction mixture with HCl as discussed above. Especially when Zazzatta teach that: “NaOH that has an alkalizing function to activate the hydroxyl groups and promote the cross-linking reaction” (Page 8, lines 14-15). Thus, it is merely following conventional synthetic steps to add a base to the reaction vessel for form an alkaline mixture, which is desirable for a cross-linking reaction, commence cross-linking, adding and disperse the calcium hydroxyapatite and then neutralize the aqueous medium with a buffering agent/HCl to bring the pH to an essentially neutral value. The selection of the order of mixing the components is obvious to the ordinary artisan. See MPEP 2144.03 IV: “See also In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946) (selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results); In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930) (Selection of any order of mixing ingredients is prima facie obvious.).” Even Molliard teaches adding the hydroxyapatite after the gel neutralization step [0050-0053]. Thus, adding the hydroxyapatite before, during or after the crosslinking is obvious to the ordinary artisan. Accordingly, the ordinary artisan has a reasonable expectation of success in so doing with the same predictable outcome.
Claims 25-26 and 35-36 are rejected under 35 U.S.C. 103(a) as being unpatentable over Gurtner et al. (WO2011109129; of record) and Zazzatta (WO2013053457; of record) and Molliard (US 20150257989; of record), as applied to claims 23-25, 27-35 and 37-43 above, in further view of Yokokawa et al. (US 20060105022; of record).
Applicant claims:
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The references of Gurtner et al., Zazzatta, and Molliard are discussed in detail above.
The combined references do not expressly teach where said cross-linking agent is poly(ethylene glycol) diglycidyl ether or ethylene glycol diglycidyl ether. However, as taught by Yokokawa et al., in the art of crosslinking hyaluronic acid, diglycidyl ether bodies such as ethylene glycol diglycidyl ether and 1,4-butanediol diglycidyl ether and the like can be used as crosslinking agents [0027]. The ordinary artisan readily understands that poly(ethylene glycol) diglycidyl ether fall under “and the like”. Thus, it is merely substitution of known crosslinking agents by the ordinary artisan with a reasonable expectation of success. "The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results." KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 417 (2007). Moreover, “Where two known alternatives are interchangeable for a desired function, an express suggestion to substitute one for the other is not needed to render a substitution obvious." In re Fout 675 F.2d 297, 301 (CCPA 1982).
In light of the forgoing discussions, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the combined references, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNST V ARNOLD whose telephone number is (571)272-8509. The examiner can normally be reached M-F 7-3:30.
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/ERNST V ARNOLD/Primary Examiner, Art Unit 1613
1 The instant specification teaches adding NaOH to the mixture [087].
2 The instant specification teaches adding HCl to neutralize the solution [089].
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