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 .
Applicant’s filing of the RCE (amendments; arguments) is acknowledged.
Claims 34,36-39,48-49,51,53-54 and 56-61 remain pending and examined on the merits following the amendments.
See also previous extensive Interview Summary. The examiner remains open to further interview to advance prosecution on the merits.
Election/Restrictions -Withdrawn
The species election is withdrawn as the examiner finds applicant’s arguments persuasive that the species are not distinct and that U.S. Patent No. 9,611,312 establishes that the means for crosslinking tropoelastin with hyaluronic acid was art-recognized.
Claim Rejections - 35 USC § 103 – Maintained,
Amendment Unpersuasive as Re-Framed: Injectable w/ Needle Capacity (27-32 Gauge) –
Not Deemed to Alter Obviousness Disposition Over Weiss I & II i/v/o Mitheux
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.
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.
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.
Claim(s) 34,36-39,48-49,51,53-54 and 56-61 remain rejected under 35 U.S.C. 103 as being unpatentable over Weiss et al. (U.S. Patent Publication No. 2012003283; “Weiss I”), in view of Weiss et al. (U.S. Patent No. 6232458; “Weiss II”), and Mitheux et al. (U.S. Patent Publication No. 20140235547).
Following the amendments, Weiss I still teaches/renders obvious and routinely optimizable the choice of concentration as to TE/HA, relevant to the now claimed concentrations of “about” 30 mg/ml:0.5% (see Weiss I para 143, Table, TE:HA ratio of 25 mg/ml:1%). The remaining teaching/suggestions are maintained for the reasons of record.
Weiss I (abstract, claims) teach injectable compositions comprising tropoelastin and a coalescence-controlling agent such as a hyaluronic acid (HA) for treating tissue defects including dermal scars arising from skin diseases/disorders such as acne, mumps, chicken pox or measles; scars from trauma such as injury or burns; or from surgical procedures. Thus, Weiss I teach from a short list that acre scars may be treatable by the instantly claimed combination. Weiss does not per se treat the concentration range.
Weiss II (abstract, claims) is relied upon for teaching the production of recombinant tropoelastins and variants thereof, which also are intended for minimizing scar formation (e.g. from severe cuts and burns, but not per se for acne scarring).
Mitheux (examples) teach a composition comprising tropelastin cross-linked to derivatized HA. Including most preferably 10 to 30 mg/ml tropoelastin to from 0.25% to 1% HA, where the cross-linking of the tropoelastin to HA assists in maintaining the tropoelastin at the site of use. Mitheux does not per teach use of such for acne scarring.
Thus, Weiss I teach the inventive concept here of treating the intended acne scarring at routinely optimizable amount, while Weiss II and Mitheux fills gaps in Weiss I by teaching variants thereof including cross-linked variants and various range amounts as routinely optimizable.
Thus, the methods and product limitations of instant claims 34, 36-37 and 49, 51, 53-54 are rendered obvious by this combination as drawn to routinely optimizable combinations and amount thereof for the intended purpose.
Claims 38-39 are drawn to steps of disrupting the skin beneath the acne scar prior to treatment which is standard practice in order to allow absorption of the agent and thus equally obvous in view of the combination.
Claim 48, 56, and 58 rendered obvious by Weiss I in view of Weiss II, the latter teaching variants of tropoelastin.
Claim 57 is rendered obvious based on Weiss I in view of Mitheux, the latter teaching derivatized HA.
Claims 59-61 are standard administration forms (injection, needle gauge, and saline solutions) employed routinely with such compositions and are equally rendered obvious based on the combination and/or the state of the art therein.
Based on this combination, the instantly claimed invention is found prima facie obvious absent a showing of secondary considerations of unexpected results employing a certain form and/or concentration of the combination claimed.
Response to Amendments and Arguments Following RCE Filed 1/23/26
Applicant’s amendments and arguments filed with the 1/23/26 RCE have been fully considered but not yet found persuasive. [See also previous extensive Interview Summary with applicant’s representatives (ARs) covering all arguments, review of test data, and next steps considerations.]
Claim Scope Amendment: The claims have been amended to expressly state that the administration route is as an injectable and that such is carried out by a needle in the 27-32 gauge size range, for treating acne. The prior art combination still renders prima facie obvious that by amendment; the arguments not providing any teaching away or evidence with valid controls of secondary considerations of unexpected results commensurate in scope thereto.
Prior Art Teachings of Record:
At a minimum, Weiss I (para’s 61, 67, and 99; claim 18.) teach the combination of TE:HA at ratios covering that claimed, exemplifying HA at 0.5% w/v, as a filler for treating acne scarring:
[0061] When the coalescence-controlling agent is hyaluronic acid, the agent may be provided in an amount of from about 0.01 to 10 percent (w/v). In a preferred embodiment, when the coalescence-controlling agent is hyaluronic acid, the agent is provided in an amount of from 0.5 to 3.5 percent (w/v).
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[0067] In further embodiments, the invention provides for a composition including tropoelastin and hyaluronic acid, wherein the mass ratio of tropoelastin to hyaluronic acid is 0.1:1 to about 500:1. In certain embodiments, the mass ratio of tropoelastin to hyaluronic acid is about 0.2:1 to about 100:1.
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18. The composition of claim 16 wherein the agent is hyaluronic acid and the mass ratio of tropoelastin to agent is about 0.2:1 to about 100:1.
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[0099] Other tissue defects to which the composition may be applied include dermal scars arising from, for example, skin diseases (such as acne . . .
At a minimum, secondary reference of record Mithieux (para’s 102 and 158) expressly teach administration of tropoelastin via a 27-31 G (gauge) needle, falling nearly exactly at the range now instantly claimed; wherein Mitheux (para’s 129-130, 216-217, claims 4-8) tropoelastin (TE) may be crosslinked to hyaluronic acid (HA) at a ratio of expressly encompassing that claimed of 30 mg/ml TE:0.5% HA as copied below:
27-32 GAUGE NEEDLE (Mithieux para’s 102 and 158)
[0102] In certain embodiments each tissue site to be treated will receive the three treatments of the product, from 1 to 24, or 2 to 12 or 3 to 6 weeks apart. The treatment may consist of multiple injections across the area to be treated, each approximately 10 mm apart in a grid formation. The treatment may be administered using a fine gauge needle, such as a 27 G, 29 G, 30 G or 31 G. The needle may be inserted into the tissue with consideration to the angle and orientation of the bevel, the depth of injection, and the quantity of material to be administered. The treatment may be injected into the tissue as a bolus, with for example a volume of 10-100 .mu.l, 10-50 ul, preferably 20 to 30 uL of product implanted at each injection site. After completion of each injection, the needle may be slowly withdrawn. When all implants have been completed the treated site may be gently massaged if required to enable the implant material to conform to the contour of the surrounding tissues. The number of treatments, the period between treatments and the amount of tropoelastin delivered at each treatment site will be adjusted based on the tissue area to be treated and the level of elasticity to be restored.
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[0158] In certain embodiments, the treatment is administered by injection of the tropoelastin composition into the mid to deep dermis by fine needle injection. The injection may be made using a hypodermic needle with a gauge of 25 G, preferably, 27 G or less, more preferably 30 G or 31 G. The injection may be made using a single syringe and needle by manual application of the treatment to the skin.
. . . FOR INJECTING
e.g. 30 mg/ml TE: 0.5% HA (Mitheux, para’s 129-130, 216-217, claims 4-8)
[0129] In certain embodiments, the treatment includes tropoelastin and a hyaluronic acid.
[0130] In certain embodiments, the tropoelastin in the composition may be cross linked to derivatised hyaluronic acid (HA). The cross-linking of the tropoelastin to a molecule such as hyaluronic acid may help to maintain the tropoelastin at the implant site according to the current invention. The composition may have from 5 to 100 mg/ml tropoelastin+0.1% to 2% HA cross-linker, preferably from 10 to 50 mg/ml tropoelastin and 0.25% to 1% HA cross-linker. Suitable formulations for the invention may include from 10 to 30 mg/ml tropoelastin cross-linked to from 0.25% to 1% HA cross-linker.
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[0216] A clinical study was undertaken using a formulation of tropoelastin lightly cross-linked with a derivatised hyaluronic acid (as described in PCT/AU2011/001503, in particular Example 3 and Example 6) compared to Restylane Vital Light (RVL--12 mg/ml hyaluronic acid cross-linked with BDDE, Q-Med, Australia). Participants were treated on the skin on the inside of the upper arm by implanting the product into the dermis by fine needle injection. The upper arm was chosen for the study as this is an area of skin which is not typically exposed to sun light and so presents as healthy undamaged skin tissue. The study aimed to assess the impact of the products on skin thickness and texture including elasticity and to gather subjective patient feedback on the appearance, naturalness and smoothness of the treated skin site.
[0217] Healthy subjects were recruited to the study and following a screening period, sixteen subjects who met the entry requirements were enrolled and randomly assigned to receive treatment with one of a range of tropoelastin formulations (ELAPR002: 10-30 mg/ml tropoelastin cross-linked to a derivatised hyaluronic acid) on one arm plus the control Restylane Vital Light (RVL--12 mg/ml hyaluronic acid cross-linked with BDDE) on the other arm. All subjects received three such treatments at the same treatment site, 3 weeks apart. Each treatment consisted of multiple injections of 20-30 ul of product delivered using a 30Gx1/4'' needle, each approximately lcm apart in a grid formation over the area upper arm.
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Claims
4. The method of claim 1 wherein the tropoelastin composition includes tropoelastin and hyaluronic acid.
5. The method of claim 1 wherein the tropoelastin is linked to hyaluronic acid.
6. The method of claim 1 wherein the composition includes from 0.5 to 50 mg/ml tropoelastin +0.1% to 1% hyaluronic acid.
8. The method of claim 1 wherein the composition is an aqueous composition that consists of tropoelastin and hyaluronic acid.
Thus, at a minimum, applicant’s amendments and arguments thereto are not yet found persuasive and the prima facie case of obviousness is maintained over the prior art combination where secondary reference Mithieux expressly teach and/or suggest all new claim amendments as to injectables in the 27-32 G (gauge) range for crosslinked TE:HA in a ratio as instantly claimed of 30 mg/ml TE:0.5% HA, and no teaching away that such would not tolerated in a fine needle of that size taught for use in Mithieux of 27-32 G.
Previously, and retained for the record as still relevant, applicant had significantly narrowed the claim scope concentrations of the two combined active agents from virtually any amount of tropoelastin (TE) to “about 30 mg/ml” and virtually any percent of hyaluronic acid (HA) to “about 0.5%”. Applicant has tested this concentration ratio of TE:HA, yet oddly had not provided any other test data on any other concentrations of TE:HA. Further, applicant had asserted unexpected results versus a non-active agent tested there against: saline. No secondary considerations of unexpected results were able to be extrapolated from the data of record which bears no valid controls and merely an assertion (as do the arguments of record) of unexpected results - absent further evidence (e.g. post-filing via declaration) as discussed with ARs (see previous Interview Summary). Further, applicant provided no rationale as to why this about 30 mg/ml:0.5% TE:HA was even selected for testing from the wide-open ranges originally claimed and protection sought for the TE:HA combination?
The closest prior art product to that now instantly claimed for which applicant may consider testing against is that of Weiss’s TE:HA 25 mg/ml:1% per para 143 Table. Applicant may wish to explore testing against this product to determine if the now claimed 30 mg/ml:0.5% yields unexpected results relevant to repairing tissue scars (as Weiss also teaches for).
As of record, primary reference Weiss teaches a combination of TE:HA of 25 mg/ml:0.5% (para 143), which nearly expressly teaches the now amended claim scope under the broadest reasonable interpretation of “about” stretching +/- 20% above the 30 mg/ml:0.5% TE:HA concentrations now claimed after amendment:
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666
421
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Even if not expressly taught, such is merely a matter of routine optimization of the concentrations for TE:HA as originally claimed here and equally disclosed in Weiss, for which Weiss equally routinely combined various amounts thereof – all of which worked, even if some more optimally than others, which is to be expected based on all parameters (including other factors such as pH, other additives, etc.). As is old law on that of concentration handed down in 1955 via In re Aller and guided by MPEP 2144.05 II A.:
“Generally, 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)”.
As originally claimed and ultimately issued in the Weiss I patent (see corresponding U.S. Patent No. 8974803, claim 19):
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213
415
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For the reasons of record, the prima facie case of obviousness is maintained, and absent further evidence as to the criticality of the now claimed TE:HA concentration of 30 mg/ml:0.5% via declaration against valid controls such as the closest prior art product to that now instantly claimed for which applicant may consider testing against is that of Weiss’s TE:HA 25 mg/ml:1% per para 143 Table. As noted above, applicant may wish to explore testing against this product to determine if the now claimed 30 mg/ml:0.5% yields unexpected results relevant to repairing tissue scars (as Weiss also teaches for).
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 MAURY AUDET whose telephone number is (571)272-0960. The examiner can normally be reached on M-Th. 7AM-5:30PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached on 571-270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
/MAURY A AUDET/Primary Examiner, Art Unit 1654
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