DETAILED ACTION
The present application is domestic application filed 20 February 2024, which is a continuation of US Application No. 17/396,597 (now abandoned), filed 06 August 2021, which is a continuation of US Application No. 14/928,634, filed 30 October 2015 (now US Patent No. 11,083,684), which is a continuation of US Application No. 13/706,221, filed 05 December 2012 (now abandoned), which is a continuation-in-part of US Application No. 13/615,193, filed 13 September 2012 (now US Patent No. 9,408,797), which is a continuation-in-part of US Application No. 13/593,313, filed 23 August 2012 (now US Patent No. 9,393,263), which is a continuation-in-part of US Application No. 13/486,754, filed 01 June 2012 (now US Patent No. 9,149,422), which claims priority to US Provisional 61/568,618, filed 08 December 2011, which claims priority to US Provisional 61/534,780, filed 14 September 2011, which claims priority to US Provisional 61/527,335, filed 25 August 2011, which claims priority to US Provisional 61/493,309, filed 03 June 2011.
The preliminary amendment filed 02 July 2024 is acknowledged. Claims 21-40 are pending in the current application and are examined on the merits herein.
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 under pre-AIA 35 U.S.C. 103(a), 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 pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 21-29 and 31-40 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Lebreton (US 2010/0028438, cited in IDS submitted 16 May 2024) in view of Fratini et al. (WO2004/067575, cited in IDS submitted 16 May 2024).
Lebreton is concerned with the preparation of hyaluronic acid (HA) based gels for use as dermal fillers, having enhanced stability and cohesivity, for example when subjected to sterilization techniques (abstract), including steam sterilization (paragraph [0023]). Soft fillers are used for treating smile lines, laugh lines, crow’s feet (i.e. periorbital region) and facial creases (i.e. wrinkles), (paragraph [0003]). Soft tissue fillers having both crosslinked and uncrosslinked HA are well known, including BDDE-crosslinked HA (para [0011], [0015]).
Lebreton teaches a preparation having crosslinked/uncrosslinked HA with an extrusion force of about 10-13 N (para [0017]). Lebreton teaches an example comprising HA gel particles mixed with free HA in an amount of 80/20 w/w (paragraph [0014]). The HA component is a cohesive, hydrated gel having no greater than about 1% to about 10% truly free HA, i.e. uncrosslinked HA or 5% to about 20% free HA (para [0018] and [0019]). The HA component is a gel comprising particles of crosslinked HA in a relatively fluidic medium of free HA, wherein the particles have an average particle size of about 250 µm (paragraph [0020]). The degree of crosslinking ranges from 5 to 6% (para [0026]). The concentration of HA ranges from about 10 mg/mL to about 40 mg/mL, including 20 mg/mL to about 30 mg/mL (para [0050]). The composition can be administered by injection via a needle with a 16-25 gauge or 25-33 gauge needle (para [0088]). Lebreton teaches “a suitable amount of free HA gel may be added to the HA/lidocaine gel mixture with the advantage of increasing the kinetics of lidocaine delivery” (paragraph [0105]).
High molecular weight HA ranges from 1,000,000 Da to 4,000,000 Da, preferably 2,800,000 Da (para [0042]). Low molecular weight HA ranges from about 200,000 Da to about 1,000,000 (para [0043]). Lebreton teaches the composition has a viscosity of about 250 Pa (paragraph [0087]).
While Lebreton teaches crosslinking HA with a bifunctional crosslinking agent, Lebreton does not expressly disclose lysine as said crosslinking agent (present claims 21, 27, 34). Lebreton does not expressly disclose comprising uncrosslinked HA with a mean molecular weight from 100 kDa to 300 kDa (present claim 24).
Fratini et al. teach a gel consisting of hyaluronic acid cross-linked with bi-functional cross-linking agents (claim 1), wherein the bifunctional cross-linking agents include L-amino acids (claim 2). The crosslinking agent include L-lysine and L-lysine methyl ester (claim 3, Example 5). The HA is crosslinked with lysine or lysine methyl ester in the presence of a carbodiimide (EDC), wherein the final product has a 10% degree of crosslinking (claim 3; Examples 5 and 6). The crosslinking is performed at a pH of 4.5, and then adjusted to 7.5 (examples 1-5). The temperature is in the range of 0-25 °C (claim 1). The final products generally have a 2-40% degree of crosslinking (p.4, lines 28-29; and claim 17). Fluid gels are obtained when HA is initially dissolved in water at a concentration between 0.5-2.5% w/w, and compact and thick gels are obtained when the concentration of HA is initially 2-2.5% w/w (paragraph [0019]). The solid product may be dissolved again in water or in physiologic solutions in different concentrations to obtain viscous solutions, gels, thin films, etc. (paragraph [0026]). The product can be sterilized, for example by filtration at 0.2 µ (p.4, line 16).
It would have been obvious at the time the invention was made to prepare a hydrogel dermal filler comprising lysine-crosslinked HA gel particles, wherein the hydrogel comprises uncrosslinked HA with a molecular weight of greater than 100,000 Da.
One having ordinary skill in the art would have been motivated to prepare a hydrogel composition comprising crosslinked HA gel particles further comprising uncrosslinked HA because Lebreton teaches the addition of uncrosslinked HA to crosslinked HA-based dermal fillers increases the kinetics of the composition. The ordinary artisan would have been motivated to incorporate an uncrosslinked HA having a mean molecular weight greater than 100,000 Da because the lowest molecular weight of HA envisioned by Lebreton is 200,000 Da. More specifically, Lebreton teaches the molecular weight of HA can range from 200,000 Da to 1,000,000 Da, or from 1,000,000 Da to 4,000,000 Da. Lebreton also teaches the hydrogel dermal filler can comprise uncrosslinked HA in an amount of 20% by weight relative to crosslinked HA. The ordinary artisan would have been motivated to optimize the overall amount of uncrosslinked HA, so that the average molecular weight of the uncrosslinked HA in the composition is greater than about 100,000 Da to affect the overall fluidity and softness of the injectable dermal filler for the treatment of wrinkles and fine lines.
Starting from Lebreton, the ordinary artisan would have looked to the teaching of Fratini et al., because Fratini et al. and Wang are concerned with preparing biocompatible crosslinked HA gels for use in the cosmetic field. The skilled artisan would have been motivated to substitute the crosslinker of Lebreton with the lysine crosslinker of Fratini et al. because lysine is bifunctional like BDDE of Lebreton, and used for crosslinking hyaluronic acid to prepare a gel for use in the cosmetic field, including tissue engineering in the derma and epidermis. See MPEP 2144.06, section II, “Substituting equivalents known for the same purpose”.
While Fratini et al. teach obtaining a fluid-like gel (water soluble), one having ordinary skill in the art would have known from Lebreton and Fratini et al. that various parameters can be modified to obtain a viscous gel, or a gel having fluid-like properties. As noted above, Lebreton expressly teach increasing the concentration of uncrosslinked HA as a means for increasing the fluidity and kinetics of the hydrogel composition. Additionally, Fratini et al. teach the initial molecular weight of HA can be higher, and the initial concentration of HA can be higher to obtain viscous solutions, gels, and thin films.
From Lebreton, the ordinary artisan would have known that crosslinked HA gels at a concentration of 20-30 mg/mL can be homogenized to a particle size on the order of 250 µm. The ordinary artisan would have been motivated to size lysine crosslinked HA because it has the same utility as the dermal filler of Lebreton, for tissue engineering in the derma and epidermis, and Lebreton teaches gel particles having this dimension can easily be extruded through a 25-33 gauge needle for use as a dermal filler.
The degree of crosslinking taught by the prior art lies within the range recited in the present claims. The pH and temperature at which the crosslinking reaction takes place as taught by Fratini et al., overlaps with the present claims.
The recitation “improving aesthetic appearance of a face” in claim 36 is an intended use of administering to the face of a subject the dermal filler of claim 36. The same applies to present claims 37-40.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Claims 30 and 31 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Lebreton (US 2010/0028438, cited above) in view of Fratini et al. (WO2004/067575, cited above) as applied to claims 21-29 and 31-40 above, and further in view of Aeschlimann et al. (US 6,630,457, cited in IDS submitted 16 May 2024).
Lebreton teaches as discussed above.
Lebreton does not expressly disclose crosslinking in the presence of NHS or sulfoNHS (present claim 30).
Fratini et al. teach as discussed above.
Aeschlimann et al. teach a matrix for a scaffold comprising a HA-crosslinked hydrogel (claims 7 and 16). Aeschlimann et al. teach coupling various bifunctional crosslinking agents to HA using EDC in the presence of NHS (schemes 3 and 4, see col. 8: 1-18). Aeschlimann et al. teach performing reactions with NHS at near neutral pH, e.g. pH 7.0 to 8.5 (col. 13:29-45).
It would have been obvious at the time the invention was made to prepare a hydrogel dermal filler comprising lysine-crosslinked HA gel particles in the presence of EDC and NHS because Fratini et al. teach crosslinking HA with lysine in the presence of EDC, and Aeschlimann et al. recognize the need for using NHS to activate the HA-intermediate.
Aeschlimann et al. teach reacting HA with EDC, followed by NHS to give an active HA-ester which is subsequently treated with an amine-based crosslinking agent. The ordinary artisan would have had a reasonable expectation of success because Fratini et al. teach crosslinking HA by first reacting HA with EDC, followed by an amine-based crosslinking agent. The ordinary artisan would have expected treating HA with EDC and then NHS would have given an activated HA-intermediate, which could then be crosslinked with lysine.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
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 21-40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 11,083,684 in view of Aeschlimann et al. (US 6,630,457, cited above).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘684 Patent are directed towards administering a dermal filler comprising lysine-crosslinked HA gel particles having a size ranging from about 10 µm to about 1000 µm, and wherein the lysine-crosslinked HA is present in the composition at a concentration of about 10 mg/mL and about 40 mg/mL, and wherein the hydrogel composition comprises uncrosslinked HA with a mean molecular weight from 100 kDa to 300 kDa.
The ‘684 Patent do not expressly disclose crosslinking in the presence of EDC and NHS or sulfoNHS (present claim 30).
Aeschlimann et al. teach a matrix for a scaffold comprising a HA-crosslinked hydrogel (claims 7 and 16). Aeschlimann et al. teach coupling various bifunctional crosslinking agents to HA using EDC in the presence of NHS (schemes 3 and 4, see col. 8: 1-18). Aeschlimann et al. teach performing reactions with NHS at near neutral pH, e.g. pH 7.0 to 8.5 (col. 13:29-45).
It would have been obvious at the time the invention was made to prepare a hydrogel dermal filler comprising lysine-crosslinked HA gel particles in the presence of EDC and NHS because Aeschlimann et al. teach using EDC/NHS to activate the HA-intermediate for crosslinking with an amine crosslinking agent.
Aeschlimann et al. teach reacting HA with EDC, followed by NHS to give an active HA-ester which is subsequently treated with an amine-based crosslinking agent. The ordinary artisan would have expected treating HA with EDC and then NHS would have given an activated HA-intermediate, which could then be crosslinked with lysine.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Conclusion
In view of the rejections to the pending claims set forth above, no claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BAHAR A CRAIGO whose telephone number is (571)270-1326. The examiner can normally be reached M-F: Noon-8pm ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Shaojia Jiang can be reached on 571-272-0627. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/BAHAR CRAIGO/
Primary Examiner
Art Unit 1699
Prosecution Insights