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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 19 December 2025 has been entered.
Response to Amendment
Claims 12, 28 and 37 have been amended, claims 1-11, 13-17, 19-21, 25, 30, 33 have been canceled and claim 38 has been newly added. Claims 12, 18, 22-24, 26-29, 31-32 and 34-38 are currently pending.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Any objection or rejection of record which is not expressly repeated in this action has been overcome by Applicant’s response and withdrawn.
Applicant’s arguments filed 19 December 2025 have been fully considered but are not deemed to be persuasive.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 12, 18, 22-24, 26-29, 31-32, 34-38 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 12, 27 and 28 recite “WOMAC pain score of from 40 to 90 points”. This recitation is indefinite because WOMAC is an art recognized index for evaluating hip and knee osteoarthritis composed of 24 items divided into 3 subgroups (pain, stiffness, physical function) and the pain component is scored as 0-20 points (total score is from 0-100). The claim limitation that the pain score is from 40-90 points is not consistent with how the WOMAC score is calculated in the art.
The specification at page 9 states:
The term "WOMAC Total score" or "WOMAC scores" herein refers to the sum of the scores obtained by a specific patient in response to the WOMAC Index questionnaire ("WOMAC" for "Western Ontario and McMaster Universities Osteoarthritis Index") which measures pain (WOMAC pain score) based on 5 items, function (WOMAC function score) based on 2 items and stiffness (WOMAC stiffness score) based on 17 items: Each item is rated based on the response (none = 0 point, mild = 1 point, moderate = 2 points, severe = 3 points, extreme = 4 points); The total WOMAC score corresponds to the sum of the rates obtained for the 24 items; The WOMAC pain score corresponds to the sum of the rates obtained for the 5 items related to pain, optionally then normalized to a 0-100 points scale (that is to say the WOMAC pain score multiplied by 5). Preferably, in the context of the invention the WOMAC pain score indicated corresponds to the WOMAC pain score normalized to a 0-100 points scale.
While claims may be read in light of the specification, limitations from the specification are not read into the claims. Furthermore, the specification is not limiting on what “WOMAC pain score” means as the specification indicates that alteration of the score is “preferably” corresponding to a normalized score. Therefore, claims 12, 27 and 28 are indefinite. Claims 18, 22-24, 26, 29, 31-32 and 34-38 are indefinite for depending on indefinite claims without correction of the issue noted in the claims from which they depend.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 12, 22-23, 26-28, 31 and 34-38 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lohmander et al. (Arthritis & Rheumatology, 66(7): 1820-1831, 2014).
Lohmander et al. teach intraarticular administration of Sprifermin (truncated FGF-18 corresponding to SEQ ID NO:2 of the instant application) to subjects with osteoarthritis. Sprifermin was administered at a dose of 100 µg in 3 doses for two cycles (see Figure 1). The subjects being treated were selected based on KL grade (2-3) as well as WOMAC scores of 24-72 (see page 1821 under “Patient enrollment”). Table 1 indicates that the mean joint space width (JSW) for the multi-dose subjects receiving the 100µg dosage was 3.51mm ± 1.25mm. While the mean was reported as being slightly greater than 3.5mm, the standard deviation indicates that some of the 63 patients who were in the 100µg multi-dose cohort had JSW less than 3.5mm.
Table 1 also provides the mean WOMAC score for the 100µg multi-dose subjects which is 53.7. The claim recites “WOMAC pain score of from 40 to 90 points”, but the WOMAC score is broken into 3 components and the pain element of the score is only scored from 0-20 (see WO 2014/023704 at page 9, cited by Applicant on IDS filed 21 November 2023). In so far as “WOMAC pain score” is interpreted as being the total WOMAC score, Lohmander et al. teach this limitation. The specification at page 9 states:
The term "WOMAC Total score" or "WOMAC scores" herein refers to the sum of the scores obtained by a specific patient in response to the WOMAC Index questionnaire ("WOMAC" for "Western Ontario and McMaster Universities Osteoarthritis Index") which measures pain (WOMAC pain score) based on 5 items, function (WOMAC function score) based on 2 items and stiffness (WOMAC stiffness score) based on 17 items: Each item is rated based on the response (none = 0 point, mild = 1 point, moderate = 2 points, severe = 3 points, extreme = 4 points); The total WOMAC score corresponds to the sum of the rates obtained for the 24 items; The WOMAC pain score corresponds to the sum of the rates obtained for the 5 items related to pain, optionally then normalized to a 0-100 points scale (that is to say the WOMAC pain score multiplied by 5). Preferably, in the context of the invention the WOMAC pain score indicated corresponds to the WOMAC pain score normalized to a 0-100 points scale.
In view of the specification, “WOMAC pain score” of the claim may be referring to the actual WOMAC pain score (on the scale of 0-20) multiplied by 5, in which case Lohmander et al. teach a mean score of 10.4 ± 2.8 for the 100µg multi-dose cohort which would be multiplied by 5 resulting in a mean score of 52, which indicates that some of the 63 patients who were in the 100µg multi-dose cohort had a WOMAC pain score between 40 and 90 points.
The subjects were evaluated for symptom efficacy including pain scores (WOMAC and VAS) as well as for cartilage thickness and volume (see page 1822, column 2, paragraphs 4-5). Lohmander et al. also teach that treatment limited cartilage thinning in the joint (see Figure 3) as well as an improvement from baseline in the WOMAC pain index score (see page 1827, first sentence of 3rd full paragraph).
With respect to claims 31-32, Lohmander et al. do not specifically indicate the JSW for each individual subject receiving treatment, however, the subjects who were selected had KL grades of 2-3. KL grades have characteristics known to those of ordinary skill in the art with regard to joint space width (as evidenced by The MARS Group, J. Bone Joint Surg. Am. 96: 1145-1151, 2014; see Table 2). In order to obtain a grade of KL3, the subject would need to have definite joint space narrowing which is defined as less than 2mm. A KL grade 2 compares with the IKDC scale which indicates that the joint space width would be 2-4 mm. In the 100µg multi-dose group, 49.2% of the subjects had a KL grade of 3 (see Table 1).
Therefore, Lohmander et al. anticipate the instant claims.
Response to Arguments
Applicant’s discussion of the invention at pages 6-12 are noted and acknowledged. Applicant references MPEP 2141.02 at page 11 with regard to this discussion. Applicant should note that MPEP 2141.02 is relevant to rejections made under 35 U.S.C. 103.
Applicant argues at page 11 with regard to the 102 rejection that Lohmander et al. does not anticipate the instant claims because Lohmander does not describe treating the claimed population of patients who have both a joint space width that is less than 3.5 mm and a WOMAC pain score that is from 40-90 points.
Applicant’s argument has been fully considered, but is not found persuasive. The claims are not directed to treating a population of patients. The claim recites “treating a human subject” and Lohmander et al. clearly treat human subjects with JSW of 3.5 or less (see Table 1) and with WOMAC pain scores between 40-90 points (see Table 1). As explained above, while the mean JSW is 3.51mm, the standard deviation is 1.25mm and the n for this group is 63 patients, indicating that there were necessarily patients with JSW<3.5mm as claimed. To the extent that the WOMAC pain score as recited in the claims means actual WOMAC pain score multiplied by 5, as described at page 9 of the specification, the mean WOMAC pain score from Lohmander was 52, i.e. between 40-90.
Applicant argues at page 12 of the response that the claimed subgroup represents a critically selected subgroup within the broader treated population of Lohmander, citing MPEP 2131.03. Applicant’s argument has been fully considered, but is not found persuasive. Lohmander et al. clearly treated patients with a JSW of less than 3.5mm as evidenced by Table 1. "If the prior art discloses a point within the claimed range, the prior art anticipates the claim." UCB, Inc. v. Actavis Labs. UT, Inc., 65 F.4th 679, 687, 2023 USPQ2d 448 (Fed. Cir. 2023).[AltContent: rect]
Applicant asserts that Lohmander’s enrollment group does not include joint space width in the cited criteria and therefore the present rejection fails to satisfy the requirements laid out under MPEP 2131. Applicant’s argument has been fully considered, but is not found persuasive. The criteria of Lohmander et al. included a KL grade of 2-3, which is explained in the rejection as corresponding to well-known JSW characteristics of 2-4mm for KL2 and less than 2mm for KL3.
Applicant argues at the bottom of page 12 that the Examiner’s reliance on the JSW data in Table 1 does not support the concept “of selecting patients having a joint space width of less than 3.5 mm” and that “a skilled worker would have no idea that patients having a joint space width of less than 3.5 mm could selectively be treated based on this disclosure”. Applicant’s argument has been fully considered, but is not found persuasive. The rejection is not based on selection of a patient with a particular JSW but rather, the fact that at least one patient with a JSW of 3.5mm or less was treated as claimed. The patient population recited in the instant claims are disclosed in Lohmander as is the treatment method and therefore, the claims are anticipated by Lohmander.
Applicant asserts at pages 12-13 that Lohmander does not report treating patients having a JSW of less than 3.5mm coupled with a WOMAC score that is from 40 to 90 points. Applicant’s argument has been fully considered, but is not found persuasive as such patients are clearly described in Table 1 as pointed out in the rejection of the claims.
Applicant argues that Lohmander did not demonstrate an improvement in WOMAC pain in the treated population and asserts that Lohmander reported that treatment with sprifermin was comparable to placebo. Applicant’s argument has been fully considered but is not found persuasive. Lohmander et al. clearly state that there “was an improvement from baseline in the WOMAC pain index score in all groups” (see page 1827, column 1, first sentence of third full paragraph).
Applicant argues at page 14 of the response that one of skill in the art would necessarily need to read Lohmander and at once envisage selecting a patient population having both a joint space width of 3.5 mm or less and a WOMAC pain score that is from 40-90 points for the treatment of osteoarthritis. Applicant argues that this criteria is not recited in Lohmander.
Applicant’s argument has been fully considered, but is not found persuasive. The rejection is not based on selecting a patient population with a given set of criteria. The rejection is based on the fact that Lohmander et al. treated patients who meet the recited limitations of the instant claims with the same recited treatment of the instant claims. The method of Lohmander et al. practiced on the patients described in the cited reference of Lohmander et al. anticipate the instant claims.
Applicant argues again at page 15 of the response that JSW is not mentioned in Lohmander et al. for enrollment. This point has been addressed in the rejection as well as in the above response to arguments. KL grade has well-known characteristics which include JSW. The rejection under anticipation is not based on selection of a patient with particular characteristics but rather, patients having the recited characteristics of the claims were treated as claimed by Lohmander et al., thereby anticipating the instant claims.
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.
Claim(s) 12, 18, 22-24, 26-29, 31-32 and 34-38 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2008/023063 (Gimona et al.) in view of WO 2015/124731 (Ladel et al.) and further in view of Moore et al. (OsteoArthritis and Cartilage 13: 623-631, 2005), Illinois Bone & Joint Institute (Arthritis in Knee: 4 Stages of Osteoarthritis)(online). Blog. Jan. 28, 2016 [retrieved 2024-02-24], Retrieved from the Internet. <URL: https://www.ibji.com/blog/orthopedic-care/arthritis-in-knee-4-stages-of-osteoartheritis/>, Kohn et al. (Clin. Orthop. Relat. Res. 474: 1886-1893, 2016) and Singh et al. J Med Ultrasound 29: 39-45, 2021.
Gimona et al. teach the treatment of cartilage disorders and osteoarthritis in particular by the administration of FGF-18 (see abstract). Gimona et al. teach that the FGF-18 compound is administered at least two times and that the administrations are separated by about 4-10 days (see page 2, last paragraph and claim 1). Gimona et al. teach that the FGF-18 compound includes wild type FGF-18 (207 amino acids) as well as FGF-18 fragment of 170 amino acids (deletion of the first 27 amino acids and truncation of the last 11 amino acids) (see page 7 and claim 17). Gimona et al. teach administration of the FGF-18 compound intraarticularly (see claim 8). Gimona et al. teach that administration of the FGF-18 compound increases cartilage deposition, which would encompass treating a symptom of a cartilage disorder because a symptom of such includes loss of cartilage (see page 8). Gimona et al. do not teach minimal joint space width or KL grades of the subjects to be treated or assess joint pain of the subjects to be treated. Additionally, Gimona et al. does not teach a dosing regimen wherein the treatment cycles are separated by about 4 to 8 months.
The Illinois Bone & Joint Institute teach that osteoarthritis can be classified into 4 stages (Stage 0 is “Normal”) and that orthopedic physicians typically do not recommend any special treatment for Stage 1 as this stage shows only very minor wear and tear and bone spur growths. In Stage 2, subjects are not demonstrating noticeable joint space width alterations but subjects begin experiencing symptoms of joint pain. The subjects do not have noticeable loss of cartilage, but proteolytic breakdown of the cartilage matrix begins. In Stage 3, subjects experience obvious erosion of the cartilage surface between bones and fibrillation narrows the gap between the bones (joint space width narrows). At this stage, there is obvious joint inflammation which causes frequent pain which may require pain-relief therapies such as over the counter NSAIDS or prescription medication such as codeine and oxycodone. Stage 4 is considered severe and presents with considerably reduced joint space, causing loss of cartilage, decreased synovial fluid and greater pain and discomfort.
Kohn et al. teach the correspondence of particular grades used for classification of osteoarthritis stages with various structural parameters of the disorder, including joint space width. Kohn et al. teach that Grade 2 corresponds to a joint space with of 2-4mm and Grade 3 corresponds to a joint space width of less than 2 mm. These grades correspond to the various stages of osteoarthritis which are well known in the art as evidenced by The Illinois Bone & Joint Institute teaching.
Singh et al. teaches that KL grades correlate to pain scores in subjects with osteoarthritis. In Table 1 at page 41, subjects with KL Grade 2 have an average pain score of 5.57 (VAS methodology) and 57.94 (WOMAC methodology). Subjects with a KL Grade 3 have an average pain score of 5.89 (VAS methodology) and 59.38 (WOMAC methodology). Subjects with a KL Grade 4 have an average pain score of 6.21 (VAS methodology) and 62.93 (WOMAC methodology).
Moore et al. (OsteoArthritis and Cartilage 13: 623-631, 2005) teach that treatment of normal rat knee joints with FGF18 did not increase chondrocyte proliferation or matrix accumulation and such treatment did not provide any significant increase in the thickness of the articular cartilage (see page 629, column 2, second paragraph). Moore et al. demonstrates that intraarticular administration of FGF18 can stimulate repair of damaged cartilage in a setting of rapidly progressive osteoarthritis. Moore et al. speculates that the difference in FGF18 effects may be related to FGF18 exerting anabolic activities specifically following injuries or may be a specific response to tissue injury. Therefore, Moore et al. teaches that FGF18 stimulates repair of damaged cartilage when there is the condition of rapidly progressive osteoarthritis and not in normal joints.
Ladel et al. teach an FGF-18 compound dosing regimen for the treatment of a cartilage disorder wherein the disorder is osteoarthritis (see claim 10) wherein the FGF-18 compound is administered at a dose of about 100 µg (see claim 8 ) and wherein the treatment cycles are repeated after 2, 3, 4, 5 or 6 months (see claim 4). Ladel et al. teach that an advantage of less frequent dosing schedules is reduced inflammation due to the injection (see page 6).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to practice the method of Gimona et al. and select subjects to be treated who are experiencing a cartilage disorder with symptoms that indicate damage to the cartilage and joint. One would be motivated to select such patients because it was well known that cartilage disorders such as osteoarthritis do not normally require treatment until they reach stage 2 and above, as evidenced by the Illinois Bone & Joint Institute teaching. One of ordinary skill in the art would be motivated to select subjects with a KL grade of 2-4 because these subjects present with reduced joint width space of 2-4mm to less than 2mm as taught by Kohn et al. as well as pain scores of more than 5 (VAS scale) or more than 57 (WOMAC scale) as taught by Singh et al. and because the prior art teaches that subjects in this stage of osteoarthritis require treatment. Furthermore, Moore et al. teaches that FGF18 stimulates repair of damaged cartilage when there is the condition of rapidly progressive osteoarthritis and not in normal joints, so one of ordinary skill in the art would necessarily select subjects who are experiencing deterioration in the joint such as subjects in stages 2-4, KL grade 2-4 which corresponds to pain scores greater than 4 or 40 (VAS and WOMAC scales, respectively).
Further it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to practice the method of Gimona et al. and apply the dosing regimen of Ladel et al. in which treatment cycles are repeated after 2-6 months to the method of Gimona et al. for the treatment of cartilage disorders in order to obtain the benefit of reduced inflammation due to the injections. One would be motivated to modify the dosing regimen because reduced inflammation would increase patient compliance. One would have had a reasonable expectation of success because based on the teachings of the combined references, various dosages and dosing regimens are successful and therefore, modification of the dosing regimen of Gimona et al. by Ladel et al. and selecting for subjects with reduced joint space width, KL grade of 2 or greater and pain of 4 or greater (VAS) or 40 or greater (WOMAC) would be expected to be successful, absent evidence to the contrary.
Response to Arguments
Applicant argues at page 16 of the response that the Examiner uses 6 references in the rejection and asserts that this fact alone would suggest the Examiner is relying on hindsight analysis in order to justify the position.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
With regard to Applicant’s assertion that the Examiner has not explained why a person of skill in the art would seek out these 6 references in order to provide the methods now claimed. Applicant’s argument has been considered but is not found persuasive. Three of the references were cited for merely pointing out the various criteria which is known in the art regarding osteoarthritis and staging of the disease (KL grades and different characteristics/criteria which is associated with the condition). While one of skill in the art would be well apprised of such characteristics/criteria, if the rejection had been written without citing such evidence the rejection would have been challenged for relying on evidence which was not in the record.
Applicant asserts at page 16 of the response that none of the cited references teach or suggest the use of sprifermin to treat osteoarthritis in subjects having a minimal joint space width of 3.5 mm or less and a WOMAC pain score of from 40 to 90 points. Applicant’s arguments have been fully considered, but are not found persuasive. The prior art clearly identifies subjects in need of treatment for osteoarthritis, as pointed out in The Illinois Bone & Joint Institute reference, Kohn et al. and Singh et al. The 4 stages of osteoarthritis are known and treatment is recommended beginning at stage 2 when the proteolytic breakdown of the cartilage matrix begins and when subjects begin experiencing joint pain. These stages correlate to joint space widths of less than 4mm (Kohn et al.) and pain scores of more than 40 points (WOMAC; see Singh et al.). One of ordinary skill in the art would be motivated to treat patients presenting with a KL grade of 2 or more with the method of Gimona et al. because these patients are experiencing rapidly progressing osteoarthritis and Moore et al. teach that FGF-18 administration during this time is therapeutic. The prior art suggests a joint space width which is less than 4mm and one can clearly envisage all widths which are in this range. Treatment of subjects with a KL grade of 3 are clearly within the scope of the claims and treatment of such subjects are clearly obvious over the references which are cited.
Claim(s) 12, 18, 28-29 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lohmander et al. in view of Ladel et al.
The teaching of Lohmander et al. is as provided above. Lohmander et al. teach intraarticular administration of Sprifermin (truncated FGF-18 corresponding to SEQ ID NO:2 of the instant application) to subjects with osteoarthritis. Sprifermin was administered at a dose of 100 µg in 3 doses for two cycles (see Figure 1). The subjects being treated were selected based on KL grade (2-3) as well as WOMAC scores of 24-72 (see page 1821 under “Patient enrollment”). The subjects were evaluated for symptom efficacy including pain scores (WOMAC and VAS) as well as for cartilage thickness and volume (see page 1822, column 2, paragraphs 4-5). Lohmander et al. do not teach a dosing regimen wherein the treatment cycles are separated by about 4 to 8 months.
Ladel et al. teach an FGF-18 compound dosing regimen for the treatment of a cartilage disorder wherein the disorder is osteoarthritis (see claim 10) wherein the FGF-18 compound is administered at a dose of about 100 µg (see claim 8 ) and wherein the treatment cycles are repeated after 2, 3, 4, 5 or 6 months (see claim 4). Ladel et al. teach that an advantage of less frequent dosing schedules is reduced inflammation due to the injection (see page 6).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to apply the dosing regimen of Ladel et al. in which treatment cycles are repeated after 2-6 months to the method of Lohmander et al. for the treatment of cartilage disorders in order to obtain the benefit of reduced inflammation due to the injections. One would be motivated to modify the dosing regimen because reduced inflammation would increase patient compliance. One would have had a reasonable expectation of success because based on the teachings of the combined references, various dosages and dosing regimens are successful and therefore, modification of the dosing regimen of Lohmander et al. by Ladel et al. would be expected to be successful., absent evidence to the contrary.
Response to Arguments
Applicant argues that the prior art does not teach selecting subjects with the recited criteria of JSW and WOMAC pain score. Applicant’s arguments have been fully considered, but are not found persuasive. The claims are directed to treating a cartilage disorder in a joint by limiting cartilage thinning in the joint. The claims recite a particular patient population, which is taught in the art as well as the ability of FGF18 to reduce/slow cartilage thinning in the joint. Applicant’s assertion that the art does not teach these two features in combination is not persuasive because the two features are characteristics which occur in combination. One of ordinary skill in the art would recognize that as JSW decreases, the WOMAC score increases in subjects with osteoarthritis. Treatment of osteoarthritis in subjects with higher WOMAC scores and lower JSW scores is well-known in the art (see references cited in the instant Office action with regard to KL grade). One of ordinary skill in the art would necessarily treat such subjects with the method of Lohmander et al. because these subjects are in need of treatment for osteoarthritis. It was known in the art that intraarticular administration of FGF18 stimulates repair of damaged cartilage in a setting of rapidly progressive osteoarthritis and not in normal joints (as evidenced by Moore et al., cited previously). Therefore, one of ordinary skill in the art would expect FGF18 to be more effective in patients with a greater loss of JSW.
Claim(s) 12, 24, 28 and 32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lohmander et al. in view of Illinois Bone & Joint Institute (cited above).
The teaching of Lohmander et al. is as provided above. Lohmander et al. teach intraarticular administration of Sprifermin (truncated FGF-18 corresponding to SEQ ID NO:2 of the instant application) to subjects with osteoarthritis. Sprifermin was administered at a dose of 100 µg in 3 doses for two cycles (see Figure 1). The subjects being treated were selected based on KL grade (2-3) as well as WOMAC scores of 24-72 (see page 1821 under “Patient enrollment”). The subjects were evaluated for symptom efficacy including pain scores (WOMAC and VAS) as well as for cartilage thickness and volume (see page 1822, column 2, paragraphs 4-5). Lohmander et al. do not teach treating a subject with a KL grade of 4.
The Illinois Bone & Joint Institute teach that osteoarthritis can be classified into 4 stages (Stage 0 is “Normal”) and that orthopedic physicians typically do not recommend any special treatment for Stage 1 as this stage shows only very minor wear and tear and bone spur growths. In Stage 2, subjects are not demonstrating noticeable joint space width alterations but subjects begin experiencing symptoms of joint pain. The subjects do not have noticeable loss of cartilage, but proteolytic breakdown of the cartilage matrix begins. In Stage 3, subjects experience obvious erosion of the cartilage surface between bones and fibrillation narrows the gap between the bones (joint space width narrows). At this stage, there is obvious joint inflammation which causes frequent pain which may require pain-relief therapies such as over the counter NSAIDS or prescription medication such as codeine and oxycodone. Stage 4 is considered severe and presents with considerably reduced joint space, causing loss of cartilage, decreased synovial fluid and greater pain and discomfort.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to practice the method of Lohmander et al. in subjects who are KL grade 4 because stage 4 is considered severe and such subjects would be considered to be in the most need of treatment. One would be motivated to select such patients because of the severity of the damage and associated pain and discomfort and such patients require treatment. One would have a reasonable expectation of success in treating these subjects because Lohmander et al. teach that the method reduces the loss of cartilage in the treated joint.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Christine J Saoud whose telephone number is (571)272-0891. The examiner can normally be reached M-F, 8am-4pm.
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/Christine J Saoud/Primary Examiner, Art Unit 1645