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 .
Receipt of amendment and response dated 08/19/25 is acknowledged.
Claims 1-18 and 20-21 have been previously canceled.
Claim 24 has been canceled by the amendment dated 0/18/25.
New claim 35 has been added.
Claims 19, 22 and 25-35 are pending.
In response to the amendment dated 8/19/25 all of the previous rejections of the record have been rewritten and applied for pending claims as follows:
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.
Claim(s) 19, 22-23, 25-27, 29 and 31-35 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2015/092740 to Bollbuck et al in view of WO2018107158 to Roinestad et al.
Instant claims have been amended to recite: A method of treating Hidradenitis suppurativa in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a LTA4H inhibitor, wherein said LTA4H inhibitor is ((S)-3-amino-4-(5-(4-(4-chlorophenoxy)-phenyl)-2H-tetrazol-2-yl)butanoic) acid or a pharmaceutically acceptable salt thereof, at a daily dose of about 10 mg to about 100 mg.
Bollbuck teaches heteroaryl butanoic acid derivatives as LTA4H inhibitors as drug candidates for treating various diseases and disorders (abstract), such as inflammatory disorders including IBD, neutrophilic dermatoses, allergy, IBD etc (page 1, 2nd paragraph).
Bollbuck teaches a compound of formula I (page 3), including embodiment 27 and further teaches the instant claimed compound, in particular (see last compound on page 10 and compound 4f on page 38) i.e., ((S)-3-amino-4-(5-(4-(4-chlorophenoxy)-phenyl)-2H-tetrazol-2-yl)butanoic) acid.
Bollbuck teaches that the compounds are used in a therapeutically effective amount and further combining one or more therapeutically active agents, for inhibiting LTA4H activity (page 11, paragraphs 1-3) for alleviating or inhibiting the disease or disorder or a condition mediated by LTA4H, or associated with LTA4H activity or characterized by activity (normal or abnormal), for reducing or inhibiting the activity of LTA4H or reducing or inhibiting the expression of LT4AH (p
Bollbuck teaches a pharmaceutically acceptable carrier including excipients such as disintegrants, binders etc (p 18, 1st full paragraph), the composition in the form of tablets, granules, capsules etc (p 21).
Bollbuck further teaches the compounds of the invention is administered in combination with other therapeutic agents, such as other anti-inflammatory agents or agents for treating autoimmune disorder, which can be administered simultaneously with or before or after administering the LTA4H inhibitors (p 71-72).
Bollbuck teaches the instant compound as a LTA4H inhibitor but fails to teach the instant claimed method of treating HS.
Roinestad teaches monoamine or monoamine derivatives as inhibitors of leukotriene A4 hydrolase (LTA4H) and in treating inflammatory disorders [0002]. Roinestad teaches that the use of LTA4H inhibitors in treating several inflammatory conditions including psoriasis, asthma, IBD, etc [0004]. In particular, Roinestad teaches that the compounds are useful for treating dermatological and mucus membrane conditions and diseases such as neutrophilic dermatoses, including Hidraenitis suppurativa (HS) [0116].
Roinestad teaches that the LTA4H inhibitor includes compounds of formula I {0009-[0024], administered in a therapeutically effective amount [0025-0026]. The composition comprising the inhibitor compound further includes pharmaceutically acceptable excipients or diluents, and administered in the form of tablets, capsules, powders, granules etc [0088]. The composition further includes binders, disintegrants, lubricants etc [0091].
Roinestad further teaches administered the LTA4H inhibitors in combination with other therapeutic agents, either concurrently or separately or for sequential administration [00103], and includes antimicrobials, analgesics etc [00104].
Therefore, it would have been obvious for one of an ordinary skill in the art before the effective filing date of the instant invention to modify the teachings of Bollbuck with that of Roinestad so as to arrive at the instant claimed method i.e., choose the LTA4H inhibitor compound 4f of Bollbuck, for effectively treating neutrophilic dermatoses including Hidraenitis suppurativa (HS), because Roinestad teaches LTA4H inhibitor compounds are effective in treating inflammatory neutrophilic dermatoses, including HS. Both Bollbuck and Roinestad constitute analogous art because both references teach treating inflammatory neutrophilic dermatoses with a therapeutically effective amount of LTA4H inhibitors. Accordingly, one of an ordinary skill in the art would have employed effective amount of the compound 4f of Bollbuck with an expectation of not only generally treating neutrophilic dermatoses but also particularly treating HS.
For claim 22-23, as explained above, both references teach the claimed pharmaceutically acceptable carriers and the claimed tablet and capsule forms.
For claim 25, as explained above, both references teach the claimed combination of additional or second therapeutic agents and in particular teaches antimicrobial agents. Therefore, one of an ordinary skill in the art would have been motivated to employ a suitable second or additional therapeutic agent, including an antiseptic agent, in the treatment of HS with the compound 4f of Bollbuck, modified by Roinestad.
Moreover, neither reference teach a prior treatment, and therefore meets claims 27.
With respect to claimed amounts of claims 19, 24 and 34-35, Bollbuck and Roinestad do not teach the claimed dose of compound 4f. However, both references teach the use of LTA4H inhibitor compounds for treating neutrophil dermatoses and Roinestad further teaches administering the compound in a range of 0.001 mg/kg – to 100mg/kg based on a 70 kg mammal [00102]. Accordingly, it would have been obvious for one of an ordinary skill in the art before the effective filing date of the instant invention to optimize the dose of compound 4f in the teachings of Bollbuck because Roinestad provides a guidance on employing a suitable range of the amounts of LTA4H inhibitor for providing an effective treatment. Therefore, choosing an optimum amount of the compound 4f for effectively treating HS for an extended period of time, would have been obvious for one of an ordinary skill in the art before the effective filing date of the instant invention. One of an ordinary skill in the art would have expected to provide at least one of the conditions a)-e) of claim 29, as well as achieve a sustained response of claim 31-33 because the combination of references suggest the claimed method and claim 19 only require administering the claimed compound to a subject in need thereof without any specific controlled or sustained release composition for providing a sustained release or the severity of HS in the subjects in need of the treatment.
Claim(s) 19, 22-23, 25-35 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2015/092740 to Bollbuck et al in view of WO2018107158 to Roinestad et al as applied to claims 19, 22-23, 25-27, 29 and 31-35 above, and further in view of Zouboulis et al (Zouboulis).
The teachings of Roinestad and Bollbuck have been discussed above, and incorporated herewith. Roinestad and Bollbuck do not teach the limitations of claims 28 and 30.
Zouboulis teaches HS is a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle that usually presents after puberty with painful, deep-seated, inflamed lesions in the apocrine gland-bearing areas of the body (introduction). The clinical presentation of HS includes recurrent inflammation, painful or suppurating lesions, bacterial infection etc (p 620). Pain in HS patients is rated using a Visual Analog scale (VAS), Numeric Rating Scale (NRS), and the influence of HS on patients’ quality of life (Qol) was evaluated with DLQI (p 621 & table 1). Zouboulis teaches that though inflammation in HS is caused by apocrine effect (p 623), that pro-inflammatory cytokines are abundantly expressed by macrophages that infiltrate papillary and reticular dermis of HS skin, and overexpression of other cytokines such as IL-1beta, CYCL9 (MIG), IL-10, IL-11 and BLC in the lesions of HS. Zouboulis further teaches the presence of bacteria such as coagulase negative staphylococci (CNS) and anerobic bacteria are the main bacteria recovered from HS lesions (p 625). With respect to treating HS, Zouboulis teaches non-antibiotics (resorcinol); antibiotic (clindamycin); antibiotic-systemic antibiotic (tetracycline, rifampicin-moxofloxacin-metronidazole); anti-inflammatory therapy with intralesional corticosteroid, systemic corticosteroids, biologics such as adalimumab; biologicals such as TNF-alpha inhibitors; retinoids, analgesics etc. (p 627-637).
Thus, it would have been obvious for one of an ordinary skill in the art before the effective filing the date of the instant invention to use the optimum amount of LTA4 inhibitor compound 4f Bollbuck for treating HS (as suggested by Roinestad) and further be able to select a subject based on the selection criteria of claims 28 and 30 i.e., experiencing moderate or severe HS, number of inflammatory lesions prior to treatment, scarring level etc., as in claim 28 because Zouboulis teaches clinical presentation of HS includes recurrent inflammation, painful or suppurating lesions, bacterial infection etc (p 620), and the pain is rated using a Visual Analog scale (VAS), Numeric Rating Scale (NRS), and the influence of HS on patients’ quality of life (Qol) was evaluated with DLQI(p 621 & table 1). Hence, one of an ordinary skill in the art would have expected that the treatment of HS with compound 4f of Bollbuck (in view of Roinestad), would have achieved any or all of the results of claim 30 i.e., at least 40% patients achieve a simplified HiSCR, at least 25% patients achieve an NRS30 response or less than 15% of said patients experience an HS flare because one of an ordinary skill in the art would have been able to select the patient having HS and further provide effective treatment with the compound of Bollbuck (in view of Roinestad).
Double Patenting
Claims 19, 22-27, 29 and 31-35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11932630 in view of WO 2015/092740 to Bollbuck et al in view of WO2018107158 to Roinestad et al and Zouboulis et al (Zouboulis).
The above patented claims are directed to a compound and a pharmaceutical composition comprising the said compound. Claim 5 of the patent recites a tetrazole compound. Claim 18 of the patent is directed to a method of treatment, including the instant claims HS, all of the patented compounds to be effective LTA4H inhibitors.
Patented claims do not recite the specific compound of instant claims 19 and the limitations of claims 22-27, 29 and 31-35.
The teachings of Bollbuck, Roinestad and Zouboulis have been discussed above and incorporated herewith.
Thus, it would have been obvious for one of an ordinary skill in the art before the effective filing the date of the instant invention to select compound 4f, which falls within the genus of claim 5 of the patented claims, which are recognized as LTA4 inhibitors, to treat subjects suffering from inflammatory conditions HS because Bollbuck teaches compound 4f on page 38) i.e., ((S)-3-amino-4-(5-(4-(4-chlorophenoxy)-phenyl)-2H-tetrazol-2-yl)butanoic) acid, for treating neutrophil dermatoses. Bollbuck recognizes the above compounds with LTA4H inhibition activity. Roinestad teaches LTA4H inhibitors for treating neutrophil dermatose, including HS. Both Bollbuck and Roinestad teach pharmaceutical compositions comprising oral dosage forms, excipients, carriers in the composition, and further Roinestad suggests doses or ranges of doses for LTA4H inhibitors in the compositions.
Accordingly, it would have been obvious for one of an ordinary skill in the art would further prepare pharmaceutical compositions comprising optimum amounts of compound 4f and additional carriers/excipients so as to prepare the compositions in the form of capsules, tablets, granules etc., with an expectation to provide an effective treatment for HS. One of an ordinary skill in the art would have expected to provide at least one of the conditions a)-e) of claim 29, as well as achieve a sustained response of claims 31-33 because the combination of references suggest the claimed method and claim 19 only require administering the claimed compound to a subject in need thereof without any specific controlled or sustained release composition for providing a sustained release or the severity of HS in the subjects in need of the treatment.
Further, Zouboulis teaches HS is a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle that usually presents after puberty with painful, deep-seated, inflamed lesions in the apocrine gland-bearing areas of the body (introduction). The clinical presentation of HS includes recurrent inflammation, painful or suppurating lesions, bacterial infection etc (p 620). Pain is in HS patients is rated using a Visual Analog scale (VAS), Numeric Rating Scale (NRS), and the influence of HS on patients’ quality of life (Qol) was evaluated with DLQI(p 621 & table 1). Zouboulis teaches that though inflammation in HS is caused by apocrine effect (p 623), that pro-inflammatory cytokines are abundantly expressed by macrophages that infiltrate papillary and reticular dermis of HS skin, and overexpression of other cytokines such as IL-1beta, CYCL9 (MIG), IL-10, IL-11 and BLC in the lesions of HS. Zouboulis further teaches the presence of bacteria such as coagulase negative staphylococci (CNS) and anerobic bacteria are the main bacteria recovered from HS lesions (p 625). With respect to treating HS, Zouboulis teaches non-antibiotics (resorcinol); antibiotic (clindamycin); antibiotic-systemic antibiotic (tetracycline, rifampicin-moxofloxacin-metronidazole); anti-inflammatory therapy with intralesional corticosteroid, systemic corticosteroids, biologics such as adalimumab; biologicals such as TNF-alpha inhibitors; retinoids, analgesics etc. (p 627-637).
Thus, it would have been obvious for one of an ordinary skill in the art before the effective filing the date of the instant invention to use the LTA4 inhibitor compound 4f Bollbuck, in the patented claims, for treating HS (as suggested by Roinestad) and further be able to select a subject based on the selection criteria of claims 28 and 30 i.e., experiencing moderate or severe HS, number of inflammatory lesions prior to treatment, scarring level etc., as in claim 28 because Zouboulis teaches clinical presentation of HS includes recurrent inflammation, painful or suppurating lesions, bacterial infection etc (p 620), and the pain is rated using a Visual Analog scale (VAS), Numeric Rating Scale (NRS), and the influence of HS on patients’ quality of life (Qol) was evaluated with DLQI(p 621 & table 1). Hence, one of an ordinary skill in the art would have expected that the treatment of HS with compound 4f (modified by Bollbuck and Roinestad), would have achieved any or all of the results of claim 31 i.e., at least 40% patients achieve a simplified HiSCR, at least 25% patients achieve an NRS30 response or less than 15% of said patients experience an HS flare because one of an ordinary skill in the art would have been able to select the patient having HS and further provide effective treatment with the compound of Bollbuck (in view of Roinestad).
Response to Arguments
Applicant's arguments filed 08/19/25 have been fully considered but they are not persuasive.
Claim Rejections — 35 USC §103
Applicants argue that the examiner has not met the threshold of a prima facie case of obviousness. It is argued that instant claim 19 now requires the amounts of claim 24, whereas the examiner made conclusory statements regarding choosing the claimed amounts of compound 4f for effectively treating HS without explaining how based on Roinestad’ s range of 0.001 mg/kg to 100 mg/kg for a general LTA4H inhibitor, one of ordinary skill in the art could have arrived at a daily dose of about 10 mg to about 100 mg of the claimed compound. It is argued that for the same reasons, the claims are nonobvious over Bollbuck in view of Roinestad. Even though they are under no obligation to submit evidence or arguments to show nonobviousness, Applicant submits that the claimed dosing regimen is the result of a phase 1 study that established safety and target engagement of LTB4. Even if a skilled artisan was motivated to combine Bollbuck and Roinestad, the artisan would not have been able to arrive at the claimed dosing regimen.
Applicants’ arguments are not found persuasive because the rejection does not make mere conclusory statements because Roinestad suggests the claimed ranges of LTA4H inhibitors for treating the claimed HS. Roinestad further suggests a range of the amount of the said inhibitor with respect to the body weight of the subject. Accordingly, the suggestion of the amounts by Roinestad provides motivation to one of an ordinary skill in the art to optimize the amount of the LTA4H inhibitors, including compound 4f of Bollbuck, based on the body weight of the subject being treated, with an expectation to provide a desired and effective HS treatment. With respect to the argument regarding the phase I trial results that results in the claimed dose, it is unclear which phase 1 results applicants are referring to. Applicants have not provided any details of the said phase I study or any comparative studies, in order to compare and evaluate the efficacy of the claimed dose. On the other hand, instant claims recite “about” 10-“about” 100 mg (claim 19) which allows for optimization of the amount of the claimed LTA4H inhibitor. Further, claims 34 and 35 also recite the term “about”, allowing optimization. Moreover, Applicants neither explain nor claim the said dose provides the claimed treatment for any body weight of the subject being treated whereas the combination of references provide motivation to optimize the dose based on the weight of the subject being treated.
Applicants’ argument that Zouboulis does not cure the deficiencies of Bollbuck or Roinestad and hence the claims are nonobvious and patentable. However, the arguments regarding Bollbuck or Roinestad have been addressed and Applicants have not provided any separate arguments regarding Zouboulis.
Applicants’ argument that the claims of US Patent 11932630 do not teach the amounts of the compound of claim 19, and as discussed above Bullock, Roinestad and Zouboulis alone or in combination fail to teach the said limitations. However, the arguments regarding Bollbuck or Roinestad have been addressed and Applicants have not provided any separate arguments regarding Zouboulis. Therefore, the Double patenting rejection has been maintained.
THIS ACTION IS MADE FINAL. 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 LAKSHMI SARADA CHANNAVAJJALA whose telephone number is (571)272-0591. The examiner can normally be reached Generally M- F 9 AM to 6 PM.
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/LAKSHMI S CHANNAVAJJALA/Primary Examiner, Art Unit 1611