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 .
Response to Amendment
Applicant’s preliminary amendment, submitted May 1, 2024, has been reviewed by the examiner and entered of record in the file. Claims 1-10 and 12-28 are amended, and claims 29-31 are newly added.
It is noted that in both the originally filed claim set of September 18, 2023 and in the amended claim set of May 1, 2024, the claims are numbered incorrectly (i.e., claim 11 is missing). Therefore, claims 12-31 should be renumbered as claims 11-30.
Information Disclosure Statement
4. The information disclosure statements (IDS) submitted on December 12, 2023, May 1, 2024, and in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112
5. 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.
6. Claims 24 and 29 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.
7. Claim 24 is indefinite because in line 3, the parenthetical phrase "for example" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
8. Claim 29 depends from claim 14, and recites the limitation "wherein the hydrophilic matric former…" in lines 1-2. However, there is insufficient antecedent basis for this limitation in the claim, because there is no recitation of a hydrophilic matric former in claim 14.
In view of a broadest reasonable interpretation, for purposes of applying prior art, claims 29 and 30 are assumed to be dependent upon claim 15.
Claim Rejections - 35 USC § 103
9. 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.
10. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
11. This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
12. Claims 1-10, 12, 17, 19, and 21, are rejected under 35 U.S.C. 103 as being unpatentable over Vossen et al., J Am Acad Dermatol (2018) (cited on Applicant’s IDS of 12/12/23), and further in view of Union Therapeutics, (webpage printout of https://www.prnewswire.com/news-releases/union- therapeutics-as-receives-fda-approval-for-ind-of-oral-next-generation-pde4-inhibitor- orismilast-for-investigation-in-plaque-psoriasis-301202575.html (2021)), (cited on Applicant’s IDS of 12/12/23).
Claim 1 is drawn to a method of treating hidradenitis suppurativa (HS), comprising orally administering (claims 5 and 12) to a human subject (claim 19) in need thereof a therapeutically effective amount of a compound of formula (I):
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or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the treatment prevents progression in a subject with moderate HS (claims 2 and 21), and wherein the treatment reduces pain (claim 3) and inflammation (claim 4) caused by or associated with HS, and
wherein the compound is administered twice daily (claim 9) at a dose of 30 mg twice per day (claim 10) but no more than 120 mg/day (claim 8), for at least 4 weeks (claim 6), but no more than 20 weeks (claim 7), and
is formulated for oral administration (claim 17).
13. Vossen et al. discuss that apremilast, an orally administered PDE4 inhibitor previously showed efficacy for the treatment of hidradenitis suppurativa, i.e., “patients with moderate-to-severe HS treated with apremilast, 30 mg twice daily for 3 months, showed a promising response,” (page 81, left column, second full paragraph). In their study, Vossen et al. demonstrate that apremilast achieved a measurable improvement in patients with moderate HS:
“a clinically meaningful improvement of moderate HS after treatment with apremilast at a dose of 30 mg twice per day for 16 weeks. Apremilast significantly decreased disease activity as measured by the AN count, and 53.3% of patients receiving apremilast achieved the HiSCR in comparison with none of the patients receiving placebo,” [emphasis added] (page 85, right column, last paragraph- page 86, left column, first paragraph). A dose of 30 mg twice daily for 16 weeks meets the limitations of claims 6-9 and 11. And, by achieving a significant decrease in disease activity, apremilast treatment is necessarily preventing disease progression (required by claim 2).
14. Vossen et al. demonstrate an overall reduction in inflammation (as measured by a reduction in abscess and inflammatory nodule (AN) count from baseline to week 16) in Figure 4, and an overall reduction in pain levels from baseline to week 16 in Figure 5 and in Table II (see pages 84-85), which meets the limitations of claims 3 and 4.
15. Vossen et al. are silent to the administration of orismilast. However, Vossen et al. go on to teach adverse events of the administration of apremilast in Table III, wherein 47% of patients reported headache, 47% of patients reported diarrhea, 36% of patients reported nausea, 36% of patients reported the common cold, 13% of patients reported vomiting, 13% of patients reported a non-specific rash (see Table III at page 86).
16. Union Therapeutics teach the advantages of the next generation PDE4 inhibitor orismilast:
“Orismilast is a next generation PDE4-inhibitor with an improved therapeutic window compared to earlier oral PDE4 inhibitors, supporting the opportunity to achieve improved efficacy while maintaining good tolerability. It holds the potential to become a best-in-class treatment and a game changer for psoriasis patients… Further, PDE4-inhibition is a well-documented pharmacological target for a number of other inflammatory indications, and we look forward to advancing our clinical research to realize the full potential of orismilast for the benefit of the millions of patients living with inflammatory conditions globally,” adds Professor Sommer.” (Page 2, second and third full paragraphs).
17. As such, one of skill in the art before the effective filing date of the claimed invention would have been motivated to modify Vossen et al. and substitute the instantly recited PDE4 inhibitor orismilast for apremilast in the treatment of hidradenitis suppurativa, with a reasonable expectation of success. And, as noted by the court in In re Font, 675 F.2d 297 (CCPA 1982), an express suggestion to substitute one equivalent component (i.e., an equivalent PDE4 inhibitor) for another is not necessary to render such substitution obvious. In the instant case, (1) the prior art element of Vossen et al. performs the function specified in the claim with only insubstantial differences; (2) the claimed component (i.e. orismilast) and its function was known in the art; (3) a person of ordinary skill in the art would have recognized the interchangeability of the elements and could have substituted one known element for another; and (4) the results of the substitution would have been predictable, i.e. a reasonable expectation of success in the treatment of HS in a subject in need thereof. Thus, it would have been obvious to one skilled in the art, having awareness that apremilast administration results in adverse events and side effects, to substitute orismilast for apremilast in the treatment of HS in a subject in need thereof, knowing that orsimilast shows improved efficacy while maintaining good tolerability.
As such, claims 1-10, 12, 17, 19, and 21 are prima facie obvious.
18. Claims 13-16 and 29-31 are rejected under 35 U.S.C. 103 as being unpatentable over Vossen et al., J Am Acad Dermatol (2018), in view of Union Therapeutics (2021), as applied to claims 1-12, 17, 19, and 21, above, and further in view of Rasmussen et al., WO 2020/148271 A1 (cited on Applicant’s IDS of 12/12/23).
Claim 1 is addressed in detail, above.
Claim 13 is drawn to claim 1, and limits wherein the compound is formulated comprises a compound of formula (I) or a pharmaceutically acceptable salt, solvate or hydrate thereof and a hydrophilic matrix former (claim 15), (more specifically 15% w/w to 25% w/w hydroxypropyl methyl cellulose (claims 16, 29 and 30), and wherein the formulation is in the form of a tablet (claim 31).
In view of a broadest reasonable interpretation, for purposes of applying prior art, claims 29 and 30 are assumed to be dependent upon claim 15.
19. Vossen et al. in view of Union Therapeutics suggest the oral administration of orismilast for the treatment of moderate HS in a subject in need thereof, but do not teach that orismilast is formulated in a modified-release tablet.
20. Yet, Vossen et al. teach that each group of patients were administered tablets, (i.e., wherein the placebo tablets are identical to apremilast):
“Eligible patients were randomly assigned to treatment with apremilast at a dose of 30 mg twice daily (n = 15) or placebo tablets with an appearance, packaging, and labeling identical to that of apremilast (n = 5).” (Page 82, left column, first full paragraph).
21. And, Rasmussen et al. teach the PDE4 inhibitor orismilast, i.e., “Compound A” (see page 3, lines 11-20) formulated in modified-release tablet formulations, comprising 30 mg orismilast and hydroxypropyl methyl cellulose in an amount of 17.5% or 15% w/w (in the form of Methocel® E50 LV) and in an amount of 25% w/w (in the form of Methocel® K100 LV), (see Table 1 at page 10).
22. Rasmussen et al. go on to demonstrate the advantages of the modified-release tablet formulations comprising 30 mg orismilast (shown in Table 1) in Example 3:
“When comparing the results shown in Figure 4 (presence of gastrointestinal related adverse events in subjects when dosed with Modified Release tablets containing the PDE4 inhibitor of formula (I)) with the results shown in Figure 5 (presence of gastrointestinal related adverse events in subjects when dosed with Immediate Release tablets containing the PDE4 inhibitor of formula (I)), the Modified Release tablet formulation study shows that the total number of gastrointestinal adverse events was clinically significantly lower when compared to the immediate release tablets.” (Page 12, last paragraph- page 13, lines 1-2).
23. As such, one skilled in the art before the effective filing date of the claimed invention would have been motivated to administer orismilast in the form of a modified- release tablet comprising hydroxypropyl methyl cellulose, in order to minimize potential gastrointestinal side effects that are associated with administration of immediate release orismilast tablets. It would have been obvious to one of skill in the art before the effective filing date of the claimed invention to administer said modified-release tablet comprising orismilast to a patient suffering from moderate HS, and one would have had reasonable expectation of success.
As such, claims 13, 15, 16 and 29-31 are prima facie obvious.
Claim 14 is drawn to claim 13, wherein the modified-release formulation releases a mean amount of from about 11 % to about 65 % of the compound of formula (I) after 45 minutes and more than 80% of the compound of formula (I) after 180 minutes when placed in a dissolution medium of 900 ml 0.5% sodium dodecyl sulfate in 0.1N HCl using Ph. Eur. 2.9.3 Apparatus II and a paddle speed of 75 rpm.
24. Claim 14 is drafted in terms of the intended outcome of the administration of the modified-release formulation of claim 13: “...wherein the modified-release formulation releases a mean amount of from about 11 % to about 65 % of the compound of formula (I) after 45 minutes and more than 80% of the compound of formula (I) after 180 minutes....” However, a claimed composition maybe obvious because it was suggested by, or structurally similar to, a prior art composition even though a particular benefit of the claimed composition asserted by patentee is not expressly disclosed in the prior art. It is the differences in fact in their respective properties which are determinative of nonobviousness. If the prior art composition does in fact possess a particular benefit, even though the benefit is not recognized in the prior art, Applicant's recognition of the benefit is not in itself sufficient to distinguish the claimed composition from the prior art, In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1991). In this case, the mean amount of compound released after 45 minutes or 180 minutes is considered a latent property of the composition disclosed by Rasmussen et al. and the alleged unexpected result of the administration, i.e., the release profile, does not confer patentability.
25. Thus, it would have been obvious to one of skill in the art before the effective filing date of the claimed invention to administer a modified-release formulation comprising orismilast to a patient suffering from moderate HS, wherein said modified-release formulation has the release profile described in claim 14, and one would have had reasonable expectation of success.
As such, claim 14 is prima facie obvious.
26. In the alternative, claim 5 and claim 18 are rejected under 35 U.S.C. 103 as being unpatentable over Vossen et al., J Am Acad Dermatol (2018), in view of Union Therapeutics (2021), as applied to claims 1-12, 17, 19, and 21, above, and further in view of ClinicalTrials.gov (webpage printout of https://www.clinicaltrials.gov/study/NCT02496546, last updated May 3, 2017), as evidenced by PubChem Compound Summary of Orismilast (webpage printout of https://pubchem.ncbi.nlm.nih.gov/compound/Orismilast, 2025), and as evidenced by Elevate: Topical Cream (Webpage printout of https://www.elevatedermrva.com/topical-cream, 2025).
Claim 1 is addressed in detail, above.
Claim 5 is drawn to claim 1, wherein treatment comprises topical administration.
Claim 18 is drawn to claim 1, and limits wherein the compound is formulated for topical administration.
27. Vossen et al. in view of Union Therapeutics suggest the administration of orismilast for the treatment of moderate HS (a chronic inflammatory skin disorder) in a subject in need thereof, but do not teach that orismilast is formulated for topical administration.
28. However, ClinicalTrials demonstrates the efficacy of topically administering LEO 32731, in the form of a topical cream comprising 20 mg/g LEO 32731, when applied daily for a duration of 3 weeks to adult subjects with atopic dermatitis (a chronic inflammatory condition of the skin), (page 1 under “Study Overview”). And, it is clear as evidenced by PubChem that LEO 32731 is also known as orismilast (page 1 under “Synonyms”).
29. ElevateDermRVA.com teaches the advantages of applying topical creams, i.e., that topical administration of formulations comprising active ingredients offers the advantage of targeted treatment, i.e., a high concentration of medication is delivered directed to the affected area of the skin with minimal systemic absorption, thereby reducing side effects. (Page 1, first paragraph).
30. As such, one of skill in the art before the effective filing date of the claimed invention would have been motivated to administer orismilast in the form of a topical cream to treat HS in a subject in need thereof, in order to deliver a higher concentration of orismilast directed to the affected area of the skin with minimal systemic absorption and reduced side effects. It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to topically administer orismilast in the form of a cream to the affected areas of the skin of a subject in need thereof, with a reasonable expectation of success.
Therefore claims 5 and 18 are prima facie obvious.
31. Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Vossen et al., J Am Acad Dermatol (2018), in view of Union Therapeutics (2021), as applied to claims 1-12, 17, 19, and 21, above, and further in view of Kerdel et al., Journal of Drugs in Dermatology (2019) (cited on Applicant’s IDS of 12/12/23).
Claim 1 is addressed in detail, above.
Claim 20 is drawn to claim 1, wherein the HS is mild HS.
32. Vossen et al. in view of Union Therapeutics suggest the oral administration of orismilast for the treatment of moderate HS in a subject in need thereof, but do not teach wherein the HS is mild.
33. Yet, Kerdel et al. teach the administration of oral apremilast to patients with mild-to-moderate HS, wherein said patients received apremilast 30mg twice daily. Kerdel et al. teach that a reduction in abscesses and nodules is shown at week 16, and suggest “that apremilast may have a role in the early treatment of less severe HS” (see abstract under “Background,” “Methods,” and “Conclusions”). Kerdel et al. teach adverse events that are consistent with those reported by Vossen et al., i.e., diarrhea (20%), nausea (15%), and depression (10%) were the most commonly reported AEs (see abstract under “Results”).
34. Therefore, one of skill in the art before the effective filing date of the claimed invention would have been motivated to modify Vossen et al. and substitute the instantly recited PDE4 inhibitor orismilast for apremilast in the treatment of mild hidradenitis suppurativa, with a reasonable expectation of success.
As such, claim 20 is prima facie obvious.
35. Claims 22, 23, 24 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Vossen et al., J Am Acad Dermatol (2018), in view of Union Therapeutics (2021), as applied to claims 1-12, 17, 19, and 21, above, and further in view of Garcovich et al., Medicine (2020) (cited on Applicant’s IDS of 12/12/23), as evidenced by Hameed et al., World J. Diabetes (2015).
Claim 1 is addressed in detail, above.
Claim 22 is drawn to claim 1, wherein the HS is severe HS.
Claim 23 is drawn to claim 1, wherein the subject is suffering from a comorbidity selected from obesity, metabolic syndrome, spondyloarthopathy, or any combination thereof.
36. Vossen et al. in view of Union Therapeutics suggest the oral administration of orismilast for the treatment of moderate HS in a subject in need thereof, but do not teach wherein the HS is severe or wherein the subject is suffering from a comorbidity.
37. Yet, Garcovich et al. report the use of ampremilast in two patients with severe HS associated with PsA and a complex comorbidity profile including type II diabetes (T2D), wherein both patients were successfully treated with apremilast (see Abstract, under “Patient Concerns”). And, it is clear as evidenced by Hameed et al. that “T2D is a metabolic disorder characterized by insulin resistance and pancreatic β-cell dysfunction as a consequence of unsettled hyperglycemia,” [emphasis added] (Page 599, left column, first paragraph under “Diabetes mellitus- not so sweet”).
38. Thus, it would have been obvious to one of skill in the art before the effective filing date of the claimed invention to modify Vossen et al. and substitute the instantly recited PDE4 inhibitor orismilast for apremilast in the treatment of severe hidradenitis suppurativa in a subject in need thereof, wherein the subject is suffering from a comorbidity that is a metabolic syndrome, with a reasonable expectation of success.
As such, claims 22 and 23 are prima facie obvious.
Claim 24 is drawn to claim 1, wherein the subject has not been previously treated with biological therapy for HS.
39. Garcovich et al. additionally describe Case 1:
“Clinical and patient-reported outcome measures included: the hidradenitis suppurativa-physician global assessment (HS-PGA = 4/severe)…. The patient had a BMI = 21.72 and was a cigarette smoker (60 pack-years). He also had numerous comorbidities including NHYA class-III congestive heart disease, type-2 diabetes, iron deficiency anemia related to chronic bleeding from fistulas, and chronic renal insufficiency. Previous treatments included systemic antibiotics (tetracyclines, rifampicin, and clindamycin) for HS, and systemic steroids and NSAIDs for PsA. Based on the clinical profile and contraindication to TNF-alpha antagonists (congestive heart disease), treatment with apremilast (30 mg twice daily) was chosen. After 16 weeks of treatment, clinical and ultrasound examinations showed reduced inflammation and HS disease activity,”
[emphasis added] (Page 2, left column, under “2.1. Case 1”). While the patient was previously treated with antibiotics, systemic steroids and NSAIDs, the patient was not treated with any biologics.
40. Therefore it would have been obvious to one of skill in the art before the effective filing date of the claimed invention to modify Vossen et al. and substitute the instantly recited PDE4 inhibitor orismilast for apremilast in the treatment of severe hidradenitis suppurativa in a subject in need thereof, wherein the subject is suffering from a comorbidity that is a metabolic syndrome, and has not been previously treated with any biological therapy, with a reasonable expectation of success.
As such, claim 24 is prima facie obvious.
Claim 25 is drawn to claim 1, wherein the subject is non-responsive or refractory to biological therapy for HS.
41. Garcovich et al. additionally describe Case 2:
“A 51-year-old man was examined for a 7-year duration, severe HS (Hurley III) involving the groins and axillae. Physical examination showed multiple sinus- tracts and nodules on the pubic, inguinal, perianal, and axillary regions (HS-PGA = 5/very severe, NRS pain score 8/10, DLQI = 25) (Fig. 2A and B). The patient was also affected by localized plaque psoriasis and peripheral PsA (DAPSA = 48.2), type-2 diabetes, hypertension, nonalcoholic steatohepatitis, and nephrolithiasis. He smoked 30 pack-years and had BMI = 24. Previous therapies with systemic antibiotics (carbapenems, cotrimaxozole, beta-lactams), cyclosporine, corticosteroids, methotrexate, retinoids, and multiple biologic agents (infliximab, etanercept, adalimumab, secukinumab) were ineffective for both PsA and HS. Extensive surgical treatment of inguinal disease was postponed due to symptomatic nephrolithiasis and high inflammatory load (CRP 6.2 mg/dl). Due to lack of efficacy of previous treatments (adalimumab) and multiple comorbidities, treatment with apremilast (30 mg twice daily) was thus initiated. Apremilast determined a clinically relevant reduction of inflammatory lesions count, effective control of skin-related pain (NRS-pain score 0/10), and QoL-improvement (DLQI = 9) after 16 weeks of treatment (Fig. 2C and D).”
(Page 2, right column, under “2.2 Case 2”). Therefore the patient was previously treated with and was non-responsive or refractory to biological therapy for HS.
42. Thus it would have been prima facie obvious to one of skill in the art before the effective filing date of the claimed invention to modify Vossen et al. and substitute the instantly recited PDE4 inhibitor orismilast for apremilast in the treatment of severe hidradenitis suppurativa in a subject in need thereof, wherein the subject is suffering from a comorbidity that is a metabolic syndrome, and is refractory to biological therapy for HS, with a reasonable expectation of success.
As such, claim 25 is prima facie obvious.
43. Claims 26 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Vossen et al., J Am Acad Dermatol (2018), in view of Union Therapeutics (2021), as applied to claims 1-12, 17, 19, and 21, above, and further in view of Goldburg et al., Journal of the American Academy of Dermatology (2020).
Claim 1 is addressed in detail, above.
Claim 26 is drawn to the method of claim 1 wherein the treatment is administered in combination with a further therapy for HS, (more specifically, wherein the further therapy for HS is selected from: from an anti-androgenic agent, a hormone, a retinoid, an anti-inflammatory agent, an analgesic, an immunosuppressive agent, an antibody, surgery, metformin, a nutritional supplement, a biological therapy for HS, a complement C5a inhibitor, a Janus Kinase (JAK) inhibitor, a leukotriene A4 hydrolase inhibitor, an IRAK4 degrader, an IRAK4 inhibitor, a tyrosine kinase 2 (TYK2) inhibitor, or a TYK2/JAK1 inhibitor or any combination thereof (claim 27)).
44. Vossen et al. in view of Union Therapeutics suggest the oral administration of orismilast for the treatment of moderate HS in a subject in need thereof, but do not teach wherein the orismilast is administered in combination with a further therapy for HS.
45. Yet, Goldburg et al. reports on known medical therapies for HS, including the immunosuppressive agents prednisone, cyclosporine, and dimethyl fumarate; hormones including spironolactone, OCP, cyproterone acetate and ethinyloestradiol, finasteride, dutasteride, and GnRH agonists; retinoids including isotretinoin, acitretin, oral alitretinoin, or etretinate; Metformin; Glp-1 agonists; and biologics including antibodies and JAK inhibitors such as etanercept, CJM-112, bimekizumab, Ustekinumab, MEDI8968, bermekimab, adalimumab, IFX, Anakinra, secukinumab, guselkumab, apremilast, and INCB054707 (see Table I at pages 4-11 and Table III at pages 16-18).
46. Thus, it would have been obvious to one of skill in the art before the effective filing date of the claimed invention to modify Vossen et al. and substitute the instantly recited PDE4 inhibitor orismilast for apremilast in the treatment of HS in a subject in need thereof, in combination with a further therapy for HS, with a reasonable expectation of success.
47. And, the rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law, please see In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings). Furthermore, MPEP 2144 teaches that the strongest rationale for combining references is a recognition, expressly or impliedly in the prior art or drawn from a convincing line of reasoning based on established scientific principles or legal precedent, that some advantage or expected beneficial result would have been produced by their combination.
48. In the instant case, two known compounds/ therapies which individually demonstrate activity against HS could be combined in order to achieve an additive effect in a method of treating HS in a subject in need thereof. Please refer to MPEP 2144.06 “I. COMBINING EQUIVALENTS KNOWN FOR THE SAME PURPOSE” wherein Kerkhoven is specifically referenced:
“It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious).
As stated by the Court in KSR International Co., v. Teleflex Inc., 127 US 1727 (2007), “when a patent ‘simply arranges old elements with each performing the same function it had been known to perform’ and yields no more than one would expect from such an arrangement, the combination is obvious” (quoting Sakraida v. AG Pro, Inc., 425 US 273 (1976); see also: Merck v. Biocraft (874 F.2d 804, 807 (Fed. Cir. 1989), indicating that it is a matter of obviousness for one of ordinary skill in the art to select a particular component from among many disclosed by the prior art as long as it is taught that the selection will result in the disclosed effect, even when the possible selections number 1200 or in the thousands; Sundance, Inc. v. DeMonte Fabricated, Ltd., 550 F.3d 1356 (Fed. Cir. 2008): a claimed invention is obvious is it is a combination of known prior art elements that would reasonably have been expected to maintain their respective properties or functions after they had been combined.
49. Thus, one skilled in the art before the effective filing date of the claimed invention would have been motivated to substitute orismilast for apremilast for treating HS in a subject in need thereof, combined with an additional therapy for HS, and would reasonably expect an additive effect in the treatment of HS in a subject in need thereof.
As such, claims 26 and 27 are prima facie obvious.
50. Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over Vossen et al., J Am Acad Dermatol (2018), in view of Union Therapeutics (2021), as applied to claims 1-12, 17, 19, and 21, above, and further in view of Schafer et al., Cellular Signaling (2014).
Claim 1 is addressed in detail, above.
Claim 28 is drawn to claim 1, wherein the treatment provides selective PDE4D or PDE4B inhibition.
51. Vossen et al. in view of Union Therapeutics suggest the oral administration of orismilast for the treatment of moderate HS in a subject in need thereof, but do not teach wherein the orismilast provides selective PDE4D or PDE4B inhibition.
52. Yet, Schafer et al. report on the pan-PDE4 inhibitory activity of apremilast, specifically naming the isoforms PDE4B and PDE4D:
“Apremilast (10 μM) displayed an average of approximately 95% (range:91%– 99%) inhibition of the PDE4 enzymes (A1A, B1, B2, C1, and D2) (Fig. 1). Apremilast did not significantly inhibit the other PDEs tested. Concentration dependent inhibition of these PDE4 isoforms was subsequently confirmed with apremilast IC50 values for PDE4A1A, PDE4B1, PDE4B2, PDE4C1, and PDE4D2 of 14, 43, 27, 118, and 33 nM. This inhibition pattern is consistent with the profile of a pan-PDE4 inhibitor,” [emphasis added] (page 2020, left column, first paragraph under “Results: 3.1 PDE Selectivity”).
53. As such, one of skill in the art would reasonably expect that orismilast, having shown an improved therapeutic window compared to earlier oral PDE4 inhibitors and having demonstrated improved efficacy for inhibiting PDE4, to possess inhibitory activity for PDE4 isoforms PDE4B and PDE4D.
54. Thus, one skilled in the art before the effective filing date of the claimed invention would have been motivated to substitute orismilast for apremilast for treating HS in a subject in need thereof, and would reasonably expect orismilast to have a selective inhibitory effect on PDE4B and PDE4D, and would have had a reasonable expectation of success in the treatment of HS in a subject in need thereof.
As such, claim 28 is prima facie obvious.
Claim Objections
55. It is noted that in both the originally filed claim set of September 18, 2023 and in the amended claim set of May 1, 2024, the claims are numbered incorrectly (i.e., claim 11 is missing). Therefore, claims 12-31 should be renumbered as claims 11-30.
Conclusion
56. In conclusion, claims 1-10 and 11-31 are pending in the instant application, and all claims are currently rejected. No claim is presently allowed.
57. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JANET L COPPINS whose telephone number is (571)272-0680. The examiner can normally be reached Monday-Friday 8:30AM-5PM EST.
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/JANET L COPPINS/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628