The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 April 17, 2026 has been entered.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.
Claims 5-7, 17-20 are canceled. Claims 1-4, 8-16, 21-29 are under consideration.
Priority: This application claims benefit of provisional applications 63/678664, filed August 2, 2024, and 63/764721, filed February 28, 2025.
Objections and Rejections
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.
Claims 1-4, 8, 13-16, 21-25 are rejected under 35 U.S.C. 103 as being unpatentable over Greenfield et al. (2023 Foot and Ankle Orthopaedics 8(4): 1-5; previously cited). Greenfield et al. disclose a method of treating plantar fibromatosis in a patient in need thereof, comprising administering or injecting a 0.45 mg collagenase formulation into the lesion to treat the plantar fibromatosis (at least p. 1-3). Greenfield et al. disclose the patient presenting with a painful, palpable, oval-shaped, golf ball-sized mass on the medial side of the plantar arch of the left foot and that physical examination demonstrated a visibly protruding, firm, well-defined mass in the subcutaneous tissues of the left plantar arch (p. 1). Greenfield et al. disclose a mass measured at 4.1 cm at maximal length, 2.2 cm in width, and 1.0 cm in thickness (p. 2). Greenfield et al. disclose that four weeks after the procedure, the patient reported greater than 50% reduction in pain compared to pretreatment, mass reduced to less than 50% of pretreatment size, noticeable size improvement 9 days after the procedure with continued gradual decrease of size of the plantar mass and reduction of foot pain over 3 months (at least p. 2). Greenfield et al. disclose that at 3 months, a residual but less bulky lesion of plantar fibromatosis, measuring 2.5 cm in length, 1.1 cm in width, 0.4 cm in thickness, indicating partial response to prior injection therapy (p. 2-3). Greenfield et al. disclose a repeat injection therapy with collagenase into the fibroma with a 0.6 mg dose (p. 3), where 4 weeks after the second injection the patient reported near complete resolution of local pain and significant reduction of palpable mass with clinically essentially normal contour of the plantar surface of the left foot (p. 3-4). Therefore, Greenfield et al. can be deemed to disclose administering a collagenase formulation as recited in the instant claims in the same amounts for treating the same disease in a subject in need thereof. Greenfield et al. differ from the claimed method by not explicitly reciting the patient’s pain intensity level based on a NRS score.
The instant specification discloses that the pain intensity based on the NRS is reported by the subject and range from 0 (no pain) to 10 (worst pain imaginable) (instant specification paragraphs 0481-0482).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at the claimed method of treating moderate to severe plantar fibromatosis in a subject in need thereof, comprising intralesionally injecting a pharmaceutical formulation comprising about 0.45 mg collagenase into one or more plantar fibromatosis nodules in the subject’s feet to thereby treat the plantar fibromatosis, wherein the subject has a pain intensity NRS score of 5-10 and the plantar fibromatosis nodule is firm throughout, and wherein the administered collagen treats and reduces a foot pain because Greenfield et al. disclose administering a collagenase formulation as recited in the instant claims in the same amounts for treating the same disease in a subject in need thereof, where the subject has similar, if not the same, pain conditions and nodule firmness recited (instant claims 1, 13). One of ordinary skill would have a reasonable expectation of success that a collagenase formulation as suggested in Greenfield et al. can be administered to successfully treat a subject having moderate to severe plantar fibromatosis, having a pain intensity NRS score of 5-10 and a plantar fibromatosis nodule that is firm throughout as recited in the instant claims, because Greenfield et al. disclose successfully treating the same disease in a patient having similar conditions, where the patient having plantar fibromatosis has a painful, palpable, oval-shaped, golf ball-sized mass that is a visibly protruding, firm, well-defined mass in the subcutaneous tissues of the left plantar arch (p. 1). Further, since Greenfield et al. disclose administering a collagenase formulation as recited in the instant claims and in the same amounts for treating the same disease in a patient in need thereof, Greenfield et al. can be deemed to disclose the same treatment properties, characteristics, and/or activities of the collagenase formulation (instant claims 1-4, 13-16).
Regarding instant claims 8, 25, Greenfield et al. also disclose a dose of 0.6 mg collagenase (p. 3).
Regarding instant claim 21, Greenfield et al. disclose the plantar fibromatosis mass measured at 4.1 cm at maximal length, 2.2 cm in width, and 1.0 cm in thickness (p. 2).
Regarding instant claim 22, Greenfield et al. disclose at least an injection of 0.6 mg collagenase formulation into a plantar fibromatosis mass measuring 2.5 cm in length, 1.1 cm in width, 0.4 cm in thickness (at least p. 3). It is known that 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). MPEP 2144.05. Therefore, it would have been obvious to one of ordinary skill to arrive at administering an injection of a collagenase formulation to a plantar fibromatosis nodule that is less than 2 cm in size by routine optimization because Greenfield et al. disclose administering a therapeutic amount of collagenase to a plantar fibromatosis nodule that is similar in size.
Regarding instant claims 23-24, as noted above, Greenfield et al. disclose the plantar fibromatosis mass measured at 4.1 cm at maximal length, 2.2 cm in width, and 1.0 cm in thickness before treatment (p. 2). Greenfield et al. disclose injecting a 0.45 mg collagenase formulation into the lesion to treat the plantar fibromatosis (at least p. 1-3) and then a second injection of 0.6 mg collagenase into the lesion (p. 3-4). Therefore, it would have been obvious to arrive at the recited two injections comprising 0.3 mg collagenase for administering to plantar fibromatosis nodules 2-4 cm in size by routine optimization because Greenfield et al. disclose repeat injections of similar therapeutic amounts of collagenase to a plantar fibromatosis nodule that is similar in size.
Reply: Applicants’ amendments/remarks have been considered but they are not persuasive. The reasons for maintaining the 103 rejection over Greenfield et al. are the same as previously noted and are incorporated herein.
Applicants assert that the office improperly mischaracterizes the claims. Applicants assert that the claims are not directed to a subject having a NRS score of 5-10 or similar level of pain. Applicants assert that rather, the claims are directed to treating a specific subset of subjects – those having moderate to severe plantar fibromatosis with a NRS score of > 5 and < 10 or having an ADP score on the pain intensity NRS score of 5-9 during the 7 days prior to treatment (claim 13), and one or more plantar fibromatosis nodules assessed at baseline palpitation to be hard or firm throughout.
Applicants’ remarks are not persuasive. The instant claims are drawn to a method for treating moderate to severe plantar fibromatosis in subject, comprising intralesionally injecting a collagenase formulation into one or more plantar fibromatosis nodules in the subject’s feet to treat the plantar fibromatosis. The instant claims further recite that the subject has a pain intensity NRS score essentially between 5-10 or 5-9 before treatment with the collagenase and that the plantar fibromatosis nodule(s) is firm throughout.
Therefore, the subjects being treated in the claims reasonably comprise subjects having a pain intensity NRS score of 5-10 and having a nodule that is firm throughout. Therefore, the interpretation of the instant claims in the 103 rejection is reasonable.
Applicants assert that Greenfield et al. do not disclose either the NRS score or the consistency of the nodule. Applicants assert that they found that the specific subset of subjects specified by the pending claims responded unexpectedly better to treatment.
Applicants’ remarks are not persuasive. As noted in the 103 rejection, Greenfield et al. disclose administering a collagenase formulation as recited in the instant claims in the same amounts for treating the same disease in a subject in need thereof, where the subject has similar, if not the same, pain conditions and nodule firmness recited.
Greenfield et al. disclose that the patient having plantar fibromatosis presents with having a painful, palpable, oval-shaped, golf ball-sized mass on the medial side of the plantar arch of the left foot and that physical examination demonstrates a visibly protruding, firm, well-defined mass in the subcutaneous tissues of the left plantar arch (p. 1). Greenfield et al. disclose significant reduction in mass size and foot pain after treatment with collagenase injected into the nodule (p. 2-4).
Therefore, Greenfield et al. can be deemed to disclose administering a collagenase formulation as recited in the instant claims in the same amounts for treating the same disease in a subject in need thereof. Greenfield et al. differ from the claimed method by not explicitly reciting the patient’s pain intensity level based on a NRS score.
As previously noted, the instant specification discloses that the pain intensity based on the NRS is reported by the subject and range from 0 (no pain) to 10 (worst pain imaginable) (instant specification paragraphs 0481-0482).
“[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). MPEP 2144.05.
In this instance, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at the claimed method of treating moderate to severe plantar fibromatosis in a subject in need thereof, comprising intralesionally injecting a pharmaceutical formulation comprising about 0.45 mg collagenase into one or more plantar fibromatosis nodules in the subject’s feet to thereby treat the plantar fibromatosis, wherein the subject has a pain intensity NRS score of 5-10 and the plantar fibromatosis nodule is firm throughout, and wherein the administered collagen treats and reduces a foot pain because Greenfield et al. disclose administering a collagenase formulation as recited in the instant claims in the same amounts for treating the same disease in a subject in need thereof, where the subject has similar, if not the same, pain conditions and nodule firmness recited.
One of ordinary skill would have a reasonable expectation of success that a collagenase formulation as suggested in Greenfield et al. can be administered to successfully treat a subject having moderate to severe plantar fibromatosis, having a pain intensity NRS score of 5-10 and a plantar fibromatosis nodule that is firm throughout as recited in the instant claims, because Greenfield et al. disclose successfully treating the same disease in a patient having similar conditions, where the patient having plantar fibromatosis has a painful, palpable, oval-shaped, golf ball-sized mass that is a visibly protruding, firm, well-defined mass in the subcutaneous tissues of the left plantar arch (p. 1). Further, since Greenfield et al. disclose administering a collagenase formulation as recited in the instant claims and in the same amounts for treating the same disease in a patient in need thereof, Greenfield et al. can be deemed to disclose the same treatment properties, characteristics, and/or activities of the collagenase formulation (instant claims 1-4, 13-16).
Applicants assert that to establish inherency, the office must establish that the patients in Greenfield et al. necessarily had moderate to severe plantar fibromatosis having the recited NRS score or ADP score on the NRS score during the 7 days prior to treatment and one or more plantar fibromatosis nodules assessed at baseline by palpitation to be hard or firm throughout. Applicants assert that simply because Greenfield et al.’s subject experienced a reduction in pain does not mean the subject necessarily had the requisite NRS score and/or nodule hardness of the subject treated in accordance with the claimed methods.
Applicants’ remarks are not persuasive. Greenfield et al. do not just disclose that the subject experiences a reduction in pain. Greenfield et al. expressly disclose a significant reduction in pain and size of the nodule following collagenase injection therapy in the subject having plantar fibromatosis. As noted above, Greenfield et al. disclose that four weeks after the procedure, the patient reported greater than 50% reduction in pain compared to pretreatment, mass reduced to less than 50% of pretreatment size, noticeable size improvement 9 days after the procedure with continued gradual decrease of size of the plantar mass and reduction of foot pain over 3 months (at least p. 2). Greenfield et al. further disclose a repeat injection therapy with collagenase into the fibroma with a 0.6 mg dose (p. 3), where 4 weeks after the second injection the patient reported near complete resolution of local pain and significant reduction of palpable mass with clinically essentially normal contour of the plantar surface of the left foot (p. 3-4).
Applicants have asserted that the specific subset of subjects recited in the instant claims responded unexpectedly better to treatment, which would reasonably include significant results in pain reduction and nodule size. Since Greenfield et al. has also disclosed the same significant results in pain reduction and nodule size in the patient having plantar fibromatosis, it would follow that the patient in Greenfield et al. is a patient having the same or similar levels of pain as recited in the instant claims.
Again, regarding Applicants’ remarks that the specific subset of subjects recited in the instant claims responded unexpectedly better to treatment (Applicants point to data and results in the instant specification), the remarks are not persuasive because Greenfield et al. also disclose significant pain reduction in the plantar fibromatosis patient treated with collagenase. Greenfield et al. disclose that four weeks after the procedure (collagenase injection 0.45 mg), the patient reported greater than 50% reduction in pain compared to pretreatment, mass reduced to less than 50% of pretreatment size, noticeable size improvement 9 days after the procedure with continued gradual decrease of size of the plantar mass and reduction of foot pain over 3 months (at least p. 2). Therefore, Applicants’ remarks that the specific subset of subjects recited in the instant claims responded unexpectedly better to treatment are not persuasive because Greenfield et al. has already disclosed the same significant results in pain reduction and nodule size are achieved by collagenase injection therapy to a patient having plantar fibromatosis experiencing pain and having a painful, firm, and well-defined nodule, which are the same disease and the same or similar levels of pain experienced by the subjects of the instant claims.
MPEP 716.02(b) notes that Applicant has the burden to establish that the results are unexpected and significant. Evidence of unexpected properties may be in the form of a direct or indirect comparison of the claimed invention with the closest prior art which is commensurate in scope with the claims. See also MPEP 716.02(e) noting that the claimed subject matter has to be compared with the closest prior art to be effective to rebut a prima facie case of obviousness.
MPEP 716.01(c) notes that objective evidence which must be factually supported by an appropriate affidavit or declaration to be of probative value includes evidence of unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor.
In this instance, Applicants have not shown or established that the results are unexpected and significant over the closest prior art Greenfield et al., which disclose administering a collagenase formulation as recited in the instant claims in the same amounts for treating the same disease in a subject in need thereof, where the subject has similar, if not the same, pain conditions and nodule firmness recited.
See also the reasons noted on at least p. 6-9 of the previous final office action of December 29, 2025.
Claims 1-4, 8, 13-16, 21-25 are rejected under 35 U.S.C. 103 as being unpatentable over Lehrman et al. (2019 The Journal of Foot and Ankle Surgery 58: 1281-1284; previously cited). Lehrman et al. disclose a method of treating plantar fibromatosis in a patient in need thereof, comprising administering or injecting 0.58 mg of collagenase into the plantar fibroma (at least p. 1282-1283). Lehrman et al. disclose the patient has pain in her left foot on weightbearing and a palpable mass along the plantar medial aspect of her left heel (p. 1282). Lehrman et al. disclose one-third of the dose of collagenase is injected into the center of the fibroma; the needle is repositioned several millimeters proximal to the initially injected dose and an additional one-third dose of the collagenase is injected into the fibroma; the needle is repositioned again and the remaining one-third dose is injected into the fibroma (at least p. 1282). Lehrman et al. disclose that at the 30-day follow-up appointment, the patient related that she had resumed all normal activities and no longer had pain in her left foot; at both the 60- and 90-day follow-up appointments, the patient reported continuing to enjoy pain-free activity and there were no findings to suggest recurrence of the plantar fibroma (at least p. 1282-1283). Therefore, Lehrman et al. can be deemed to disclose administering a collagenase formulation as recited in the instant claims in the same amounts for treating the same conditions in a subject in need thereof. Lehrman et al. differ from the claimed method by not explicitly reciting the patient’s pain intensity level based on a NRS score.
The instant specification discloses that the pain intensity based on the NRS is reported by the subject and range from 0 (no pain) to 10 (worst pain imaginable) (instant specification paragraphs 0481-0482).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at the claimed method of treating moderate to severe plantar fibromatosis in a subject in need thereof, comprising intralesionally injecting a pharmaceutical formulation comprising about 0.58 mg collagenase into one or more plantar fibromatosis nodules in the subject’s feet to thereby treat the plantar fibromatosis, wherein the subject has a pain intensity NRS score of 5-10 and the plantar fibromatosis nodule is firm throughout, and wherein the administered collagen treats and reduces a foot pain because Lehrman et al. disclose administering a collagenase formulation as recited in the instant claims in the same amounts for treating the same disease in a subject in need thereof, where the subject has similar, if not the same, pain conditions and nodule firmness recited (instant claims 1, 13). One of ordinary skill would have a reasonable expectation of success that a collagenase formulation as suggested in Lehrman et al. can be administered to successfully treat a subject having moderate to severe plantar fibromatosis, having a pain intensity NRS score of 5-10 and a plantar fibromatosis nodule that is firm throughout as recited in the instant claims, because Lehrman et al. disclose successfully treating the same disease in a patient having similar conditions, where the patient having plantar fibromatosis has pain in the left foot upon bearing weight and a plantar fibroma that is a palpable lump and pain on weightbearing (p. 1282-1283). Further, since Lehrman et al. disclose administering a collagenase formulation as recited in the instant claims and in the same amounts for treating the same disease in a patient in need thereof, Lehrman et al. can be deemed to disclose the same treatment properties, characteristics, and/or activities of the collagenase formulation (instant claims 1-4, 13-16).
Regarding instant claims 8, 25, Lehrman et al. also disclose a dose of 0.58 mg collagenase, which is about the recited 0.6 mg/mL (p. 3).
Regarding instant claims 21-22, Lehrman et al. disclose injecting 0.58 mg collagenase into a plantar fibroma (p. 1282-1283), which successfully treated the plantar fibroma. It is known that 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). MPEP 2144.05. Therefore, it would have been obvious to one of ordinary skill to arrive at administering an injection of a collagenase formulation to a plantar fibromatosis fibroma that is a suitable size, including less than 4 cm or 2 cm in size, by routine optimization because Lehrman et al. disclose administering a therapeutic amount of collagenase to a plantar fibroma that is visible having a definite mass and is successfully treated.
Regarding instant claims 23-24, Lehrman et al. Lehrman et al. disclose administering 0.58 mg of collagenase into the plantar fibroma in one-third injections (at least p. 1282-1283). Therefore, it would have been obvious to arrive at the recited two injections comprising 0.3 mg collagenase for administering to plantar fibromatosis nodules 2-4 cm in size by routine optimization because Lehrman et al. disclose repeat injections of similar therapeutic amounts of collagenase to plantar fibromatosis nodules that are visible having a definite mass.
Reply: Applicants’ amendments/remarks have been considered but they are not persuasive. The reasons for maintaining the 103 rejection over Lehrman et al. are the same as previously noted and are incorporated herein. Lehrman et al. is maintained for the reasons similarly noted above for Greenfield et al.
Applicants assert that the office improperly mischaracterizes the claims. Applicants assert that the claims are not directed to a subject having a NRS score of 5-10 or similar level of pain. Applicants assert that rather, the claims are directed to treating a specific subset of subjects – those having moderate to severe plantar fibromatosis with a NRS score of > 5 and < 10 or having an ADP score on the pain intensity NRS score of 5-9 during the 7 days prior to treatment (claim 13), and one or more plantar fibromatosis nodules assessed at baseline palpitation to be hard or firm throughout.
Applicants’ remarks are not persuasive. The instant claims are drawn to a method for treating moderate to severe plantar fibromatosis in subject, comprising intralesionally injecting a collagenase formulation into one or more plantar fibromatosis nodules in the subject’s feet to treat the plantar fibromatosis. The instant claims further recite that the subject has a pain intensity NRS score essentially between 5-10 or 5-9 before treatment with the collagenase and that the plantar fibromatosis nodule(s) is firm throughout.
Therefore, the subjects being treated in the claims reasonably comprise subjects having a pain intensity NRS score of 5-10 and having a nodule that is firm throughout. Therefore, the interpretation of the instant claims in the 103 rejection is reasonable.
Applicants assert that Lehrman et al. do not disclose either the NRS score or the consistency of the nodule. Applicants assert that they found that the specific subset of subjects specified by the pending claims responded unexpectedly better to treatment.
Applicants’ remarks are not persuasive. As noted in the 103 rejection, Lehrman et al. disclose administering a collagenase formulation as recited in the instant claims in the same amounts for treating the same disease in a subject in need thereof, where the subject has similar, if not the same, pain conditions and nodule firmness recited.
Lehrman et al. disclose that the patient having plantar fibromatosis presents with having pain in her left foot on weightbearing and a palpable mass along the plantar medial aspect of her left heel (p. 1282). As previously noted, it would be obvious that the plantar fibromatosis nodule in the subject in Lehrman et al. is firm throughout because Lehrman et al. disclose a plantar fibroma that is a palpable lump and pain on weightbearing (p. 1282). This is further evidenced in the prior art, which disclose that the characteristic sign of a plantar fibroma is a noticeable lump in the arch that feels firm to the touch (American College of Foot and Ankle Surgeons on Plantar Fibroma, 2010, p. 1). Lehrman et al. disclose that after the collagenase injection therapy, at the 30-day follow-up appointment, the patient related that she had resumed all normal activities and no longer had pain in her left foot; at both the 60- and 90-day follow-up appointments, the patient reported continuing to enjoy pain-free activity and there were no findings to suggest recurrence of the plantar fibroma (at least p. 1282-1283).
Therefore, Lehrman et al. can be deemed to disclose administering a collagenase formulation as recited in the instant claims in the same amounts for treating the same disease in a subject in need thereof. Lehrman et al. differ from the claimed method by not explicitly reciting the patient’s pain intensity level based on a NRS score.
As previously noted, the instant specification discloses that the pain intensity based on the NRS is reported by the subject and range from 0 (no pain) to 10 (worst pain imaginable) (instant specification paragraphs 0481-0482).
“[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). MPEP 2144.05.
In this instance, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at the claimed method of treating moderate to severe plantar fibromatosis in a subject in need thereof, comprising intralesionally injecting a pharmaceutical formulation comprising about 0.58 mg collagenase into one or more plantar fibromatosis nodules in the subject’s feet to thereby treat the plantar fibromatosis, wherein the subject has a pain intensity NRS score of 5-10 and the plantar fibromatosis nodule is firm throughout, and wherein the administered collagen treats and reduces a foot pain because Lehrman et al. disclose administering a collagenase formulation as recited in the instant claims in the same amounts for treating the same disease in a subject in need thereof, where the subject has similar, if not the same, pain conditions and nodule firmness recited.
One of ordinary skill would have a reasonable expectation of success that a collagenase formulation as suggested in Lehrman et al. can be administered to successfully treat a subject having moderate to severe plantar fibromatosis, having a pain intensity NRS score of 5-10 and a plantar fibromatosis nodule that is firm throughout as recited in the instant claims, because Lehrman et al. disclose successfully treating the same disease in a patient having similar conditions, where the patient having plantar fibromatosis has pain in the left foot upon bearing weight and a plantar fibroma that is a palpable lump and pain on weightbearing (p. 1282-1283). Further, since Lehrman et al. disclose administering a collagenase formulation as recited in the instant claims and in the same amounts for treating the same disease in a patient in need thereof, Lehrman et al. can be deemed to disclose the same treatment properties, characteristics, and/or activities of the collagenase formulation (instant claims 1-4, 13-16).
Applicants assert that to establish inherency, the office must establish that the patients in Lehrman et al. necessarily had moderate to severe plantar fibromatosis having the recited NRS score or ADP score on the NRS score during the 7 days prior to treatment and one or more plantar fibromatosis nodules assessed at baseline by palpitation to be hard or firm throughout. Applicants assert that simply because Lehrman et al.’s subject experienced a reduction in pain does not mean the subject necessarily had the requisite NRS score and/or nodule hardness of the subject treated in accordance with the claimed methods.
Applicants’ remarks are not persuasive. Lehrman et al. do not just disclose that the subject experiences a reduction in pain. Lehrman et al. also disclose significant pain reduction in the plantar fibromatosis patient treated with collagenase. As noted above, Lehrman et al. disclose that at the 30-day follow-up appointment, the patient related that she had resumed all normal activities and no longer had pain in her left foot; at both the 60- and 90-day follow-up appointments, the patient reported continuing to enjoy pain-free activity and there were no findings to suggest recurrence of the plantar fibroma (at least p. 1282-1283).
Applicants have asserted that the specific subset of subjects recited in the instant claims responded unexpectedly better to treatment, which would reasonably include significant results in pain reduction and nodule size. Since Lehrman et al. has also disclosed the same significant results in pain reduction and nodule size in the patient having plantar fibromatosis, it would follow that the patient in Lehrman et al. is a patient having the same or similar levels of pain as recited in the instant claims.
Again, regarding Applicants’ remarks that the specific subset of subjects recited in the instant claims responded unexpectedly better to treatment (Applicants point to data and results in the instant specification), the remarks are not persuasive because Lehrman et al. also disclose significant pain reduction in the plantar fibromatosis patient treated with collagenase. Lehrman et al. disclose that at the 30-day follow-up appointment (after collagenase injection therapy), the patient related that she had resumed all normal activities and no longer had pain in her left foot; at both the 60- and 90-day follow-up appointments, the patient reported continuing to enjoy pain-free activity and there were no findings to suggest recurrence of the plantar fibroma (at least p. 1282-1283). Therefore, Applicants’ remarks that the specific subset of subjects recited in the instant claims responded unexpectedly better to treatment are not persuasive because Lehrman et al. has already disclosed the same significant results in pain reduction and nodule size are achieved by collagenase injection therapy to a patient having plantar fibromatosis experiencing pain and having a painful, firm, and well-defined nodule, which are the same disease and the same or similar levels of pain experienced by the subjects of the instant claims.
MPEP 716.02(b) notes that Applicant has the burden to establish that the results are unexpected and significant. Evidence of unexpected properties may be in the form of a direct or indirect comparison of the claimed invention with the closest prior art which is commensurate in scope with the claims. See also MPEP 716.02(e) noting that the claimed subject matter has to be compared with the closest prior art to be effective to rebut a prima facie case of obviousness.
MPEP 716.01(c) notes that objective evidence which must be factually supported by an appropriate affidavit or declaration to be of probative value includes evidence of unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor.
In this instance, Applicants have not shown or established that the results are unexpected and significant over the closest prior art Lehrman et al., which disclose administering a collagenase formulation as recited in the instant claims in the same amounts for treating the same disease in a subject in need thereof, where the subject has similar, if not the same, pain conditions and nodule firmness recited.
See also the reasons noted on at least p. 12-16 of the previous final office action of December 29, 2025.
Claims 1-4, 8, 9-12, 13-16, 21-25, 26-29 are rejected under 35 U.S.C. 103 as being unpatentable over Greenfield et al. (2023 Foot and Ankle Orthopaedics 8(4): 1-5; previously cited) or Lehrman et al. (2019 The Journal of Foot and Ankle Surgery 58: 1281-1284; previously cited) in view of Mclane et al. (WO 2020058755; IDS 08.22.25, previously cited). The teachings of Greenfield et al. or Lehrman et al. over at least instant claims 1-4, 8, 13-16, 21-25 are noted above.
Both Greenfield et al. and Lehrman et al. disclose a method of treating plantar fibromatosis in a patient in need thereof, comprising injecting a dose of about 0.45 mg or about 0.6 mg collagenase formulation into a plantar fibroma of the patient (see above).
Mclane et al. disclose collagenase formulations for injection are in about 0.01 mg to about 20 mg single doses or divided doses and have characteristic including 500 to 30,000 SRC units/mg and potencies 100,000 to 400,000 GPA units/mg and/or 175,000 to 500,000 f-GPA units/mg (at least p. 6-7).
It is known that 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). MPEP 2144.05.
Regarding instant claims 9-12, 26-29, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate known dosages and/or potencies of collagenase formulations available in the prior art and as disclosed in Mclane et al. for the collagenase formulations disclosed in the method for treating plantar fibromatosis of Greenfield et al. or Lehrman et al. and arrive at the recited potencies by routine optimization because collagenase formulations for injection at the doses and potencies were available in the prior art and it was further known collagenase formulations for injection are effective for treating plantar fibromatosis in subjects having pain and a firm nodule.
Reply: Applicants’ amendments/remarks have been considered but they are not persuasive. The reasons for maintaining Greenfield et al. and Lehrman et al. are the same as noted above.
Regarding Applicants’ remarks on Mclane et al., the remarks are not persuasive. The deficiency of Mclane et al. to not teach patients with plantar fibromatosis and plantar fibromas and having pain are remedied by the teachings of Greenfield et al. or Lehrman et al. noted above.
No claim is allowed.
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/Marsha Tsay/Primary Examiner, Art Unit 1656
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