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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 26 May 2026 has been entered.
DETAILED OFFICE ACTION
This Office Action is in response to the papers filed on 25 November 2025.
PRIORTY
The Applicant claims priority to Provisional Applications 62/697376 (filed on 7/12/2018) and 62/733046 (filed on 9/18/2018). The Provisional Applications do not provide support for the SRC and GPA assays and all of the molecular mass ranges recited in claim 1. The Provisional Applications do not provide support for a depth of 1/8 inch to 2 inches at about a 30 degree angle. Foreign Priority document PCTIB2019000767, filed on 11 July 2019, provides support for a change in score from baseline to Day 71 of about -0.1 to about -2.0 ([section 19 of 000264]). The foreign priority document provides support for the injection angle recited in claim 1. The foreign priority document does not provide support for a depth of 1/8 inch to 2 inches at about a 30 degree angle. The Non-Provisional Application filed on 01/12/2021 provides support for this limitation in Table 15.
CLAIMS UNDER EXAMINATION
Claims 1-3, 5-8 and 11-12 are pending and have been examined on their merits.
REJECTIONS
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-3, 5-8 and 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Hart et al. (previously cited; Method of Treating Or Reducing EFP. US20140335072 2014) in view of PR Newswire (previously cited; Endo Announces Positive Data from Phase 2b Study of Collagenase Clostridium Histolyticum (CCH) in Patients with Cellulite 17 November 2016) and Plastic Surgery Practice (Uncovering the Myth of Mesotherapy. 2005 pages 1-11) as evidenced by Sabatino et al. (previously cited; Compositions and methods for treating collagen-mediated diseases. Patent 7811560).
Hart teaches a method of treating or reducing Edematous fibrosclerotic panniculopathy (EFP; cellulite) comprising administering injections of collagenase to an area affected by EFP (Abstract; [0002]). The art teaches one or more low dose injections of collagenase ([0005]). Women (humans) are treated ([0045]). Hart treats the thigh ([0047]). Hart analyzes cellulite using an EFP (cellulite) severity scale (CSS) [0020]. Hart teaches the extent of collagen lysis is proportional to the dose volume injected ([0040]).
Hart uses a syringe with a needle to administer a dose of Collagenase Clostridium Histolyticum ([0059]). At each of the 10 sites, study drug wis injected perpendicular to the subject's skin to a depth of ¼ inch (~ 7mm; between a depth of 1/8 inch to 2 inches) ([0059]). “Perpendicular” is interpreted to be a 90° angle to a surface.
Regarding the characteristics of the collagenase:
The collagenase has a purity of at least 95% determined by HPLC ([0024]). Therefore Hart meets the limitations of the characteristic vii of claim 1. Hart discloses a collagenase comprising a combination of collagenases AUX I and AUX II derived from fermentation by Clostridium histolyticum ([0024]). As evidenced by the PG Pub of the instant Specification, Aux-I and AUX-II have characteristics i, ii, iv and v of claim 1 ([0203]). Therefore the composition taught by Hart would possess these characteristics.
Hart does not disclose the presence of lostripain, gelatinase or leupeptin. Therefore Hart meets the limitations of the characteristic xi of claim 1.
Hart discloses the contents of “US Patent 7811560 are expressly incorporated herein by reference herein” ([0024]). Examiner notes this patent is Sabatino et al. Regarding the bodily incorporation of US Patent 7811560 (Sabatino et al):
Sabatino teaches a drug consisting of collagenase I and collagenase II having the sequence of Clostridium histolyticum collagenase I and collagenase II, respectively, having a mass ratio of about 1 to 1 with a purity of greater than at least 95% by area (Abstract; see column 81, lines 45-49). Purity is determined by RP-HPLC (reverse phase high performance liquid chromatography (See Table A at Column 19). This meets the limitations of characteristic vii of instant claim 1. The composition comprises less than 1 cfu/ml bioburden and less than or equal to 1% by area of clostripain and gelatinase (see same section). This meets the limitations of characteristics xi and xii of instant claim 1. The composition comprises 13,000-23,000 fSRC units/mg AUX I collagenase (see same section). This reads on characteristic viii of instant claim 1. The composition comprises 230000-430000 fGPA units/mg AUX II collagenase (same cited section). This reads on characteristic ix of instant claim 1. Therefore the composition taught by Hart possesses the characteristics disclosed in the Sabatino reference.
The deficiencies of Hart are: The art does not teach the claimed change in Hexsel Depression Depth Score. The art does not teach injection at the angle recited in claim 1.
PR Newswire (Endo) teaches a method of using clostridium histolyticum (CCH) for the treatment of cellulite (page 1, first paragraph). The disclosure teaches CCH is known in its currently approved indications in the U.S. as XIAFLEX (same cited section). The disclosure teaches the following (see last paragraph of page 3 bridging first paragraph of page 4):
The Phase 2b trial enrolled 375 women with moderate or severe cellulite aged 18 years or older in the United States. Each subject received up to three treatment sessions of CCH (0.84 mg / session) or placebo with each treatment session occurring approximately 21 days apart. Twelve injections were administered into cellulite dimples during each session across an entire treatment quadrant – left or right buttock or left or right posteriolateral thigh. At both the outset and conclusion of the study period (28 days after the last treatment), cellulite severity was assessed by each patient and clinician using two photonumeric cellulite severity scales developed by Endo and third-party experts. The scales – the Photonumeric Cellulite Severity Scale (PCSS) – are 5-point scales ranging from 0 (no cellulite) to 4 (severe cellulite) that measure improvement in the appearance of cellulite.
The endpoint of the study is Day 71 (see page 4, second paragraph). Improvement is assessed using changes in the Hexsel cellulite severity scale (same cited section).
The disclosure teaches a highly significant proportion of CCH subjects were reported as "Improved" or "Very Improved" or "Very Much Improved" in global appearance of their cellulite area (see page 5, bullet point 4).
Plastic Surgery Practice (PSP) teaches mesotherapy is a treatment which injects low doses of drugs into the skin (see page 2). Drugs are administered into the most superficial skin layers (see last paragraph of page 2).The art teaches manual application of superficial injections, the needle is inserted at an angle of approximately 30 degrees, and the medicine is deposited at a dept of 3 mm (see page 5). The art teaches mesotherapy for cellulite treatment (see page 8).
It would have been obvious to use the Hexsel CSS to analyze dimple depth. One would have been motivated to do so since Hart uses a CSS to analyze dimple depth and PR Newswire uses the Hexsel CSS to analyze changes in cellulite dimples. One would perform analysis at day 71 since PR Newswire teaches doing so for CSS analysis following collagenase treatment. One would have had a reasonable expectation of success since PR Newswire teaches Hexsel CSS can be used to analyze a thigh treated with collagenase at day 71.
It would have been obvious to combine the teachings of the prior art by inserting the syringe at about a 30°angle. Hart teaches a method of treating thigh cellulite by injecting a low dose of therapeutic into the skin and Plastic Surgery Practice teaches mesotherapy injects low doses of drugs into the skin at an angle of about 30 degrees. One would have been motivated to use this angle for manual injection. The skilled artisan would treat without fully moving the needle from the skin to ensure the entire therapeutic dose is administered to the surface of the epidermis. One would have had had a reasonable expectation of success since Plastic Surgery Practice mesotherapy for cellulite treatment.
It would have been obvious to optimize the number of aliquots administered. One would do so to delivered the desired amount of therapeutic to the treatment site. One would have had a reasonable since Hart teaches the extent of collagen lysis is proportional to the dose volume injected. One would administer additional volumes (hence, aliquots) of the therapeutic to achieve the desired amount of collagen lysis. One would have had a reasonable expectation of success since both Hart and PR Newswire teach multiple doses (aliquots) can be administered. Because the claimed method is rendered obvious, it would be expected to result in the claimed changed in Hexsel Depression Depth Score at Day 71. Therefore claim 1 is rendered obvious.
Injecting 5 aliquots is rendered obvious on the grounds set forth in the rejection of claim 1 above. Therefore claim 2 is included in this rejection.
Because the composition taught by Hart comprises AUX-I and AUX-II, it would be expected to have the characteristics recited in claim 3. Therefore claim 3 is rejected.
As set forth above, the composition taught by Hart meets the limitations of characteristics i, vii, xi and xii. As evidenced by the Instant Specification at [0203]) Aux-I and AUX-II have characteristics i, ii, iv and v of claim 1. Therefore the composition taught by Hart has at least 5 of the characteristics recited in claim 1. Therefore claims 5-7 are rejected.
Sabatino, which is incorporated by Hart, identifies cellulite as a collagen mediated-disease that may be treated by the disclosed composition (column 21, line 7). The art disclose an exemplary formulation comprising a 0.9 mg drug substance dose (column 24, line 13). 0.9 mg of collagenase is interpreted to be about 1 mg. Therefore claim 8 is included in this rejection.
Hart teaches a collagenase composition for treating cellulite. As set forth above, Hart teaches a collagenase comprising collagenase I and II from Clostridium in a 1:1 ratio with a purity of at least 95%. Examiner notes the Instant Specification discloses a collagenase composition from Clostridium hystoliticum comprising collagenase I and II with the same purity ([00457]). The potency is between 5,000 to about 25,000 ABC units ([0471]). Absent evidence to the contrary, the collagenase taught by Hart is expected to have the potency recited in claim 11. Hart does not explicitly teach administering a dose of about 1 mg as recited in claims 11-12.
PR Newswire teaches subjected receive up to three treatment sessions of CCH at 0.84 g/session (see page 3, last paragraph). While the specification defines the term “about” (supra), it does not disclose the values encompassed by the term “about”. Therefore 0.84 mg is broadly interpreted to read on about 1 mg. It would have been obvious to administer about 1 mg of the claimed collagenase to treat cellulite. One would have been motivated to do so since Hart administers collagenase to treat cellulite and PR Newswire teaches about 1 mg collagenase can be administered to treat cellulite. One would have had a reasonable expectation of success since PR Newswire teaches this amount can be administered to treat cellulite. One would have expected similar results since both references are directed to a method of treating cellulite in a thigh using collagenase. Therefore claim 11 is rendered obvious.
The Hart reference incorporates the contents of the Sabatino Patent. The Sabatino Patent teaches a collagenase composition comprising 0.9 mg collagenase. This is interpreted to be about 1 mg. Sabatino teaches the composition comprises 13,000-23,000 fSRC units/mg AUX I collagenase (see same section). Because neither the instant claims nor specification disclose the values encompassed by the term “about”, Sabatino is broadly interpreted to read on about 20,000 to about 30,000 fSRC units/mg.
Sabatino teaches the composition comprises 230000-430000 fGPA units/mg AUX II collagenase. Because neither the instant claims nor specification disclose the values encompassed by the term “about”, Sabatino is broadly interpreted to read on about 175,000 to about 300,000 f-GPA units/mg. It would have been obvious to administer about 1 mg collagenase to treat cellulite for the reasons set forth in the rejection of claim 11. Therefore claim 12 is rendered obvious.
Therefore Applicant’s Invention is rendered obvious as claimed.
RESPONSE TO APPLICANT’S ARGUMENTS
The arguments made in the response filed on 26 May 2026 are acknowledged.
Argument 1: The Applicant argues the cited references do not teach the claimed injection angle.
Response to Argument 1: New grounds of rejection have been made to address the amended claim.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE MOSS whose telephone number is (571) 270-7439. The examiner can normally be reached on Monday-Friday, 8am-5pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached on (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is (571) 270-8439.
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/NATALIE M MOSS/ Examiner, Art Unit 1653
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