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 .
Priority
This application was filed on and is a U.S. national Stage application under 35 U.S.C. 371 of International Patent Application No. PCT/US2020/051438 filed 09/18/2020, which claims the benefit of the priority of US Provisional application 62/903,376 filed 09/20/2019.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Status
Claims 1-13 are canceled. Claims 14-16, 18-19 are amended. Claims 22-26 are new. Claims 14-26 are being examined on the merits in this office action.
Claim Rejections - Withdrawn
The rejection of claims 14-19, and 21-22 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in view of the claim amendments.
Claim Rejections - 35 USC § 103 – Maintained and Modified
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.
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.
Claims 14-17, and 20-26 remain rejected under 35 U.S.C. 103 as being unpatentable over Anzali et al. (US 2011/0027209A1 – hereinafter “Anzali”- cited and enclosed in the previous office action) as evidenced by Prignano et al. (Clin. Cosmet. Investig. Dermatol. 2009 Feb 19;2: 9–13- cited and enclosed in the previous office action), in view of Monleon et al. (Biochem. J. (2005) 387, 57–66- cited and enclosed in the previous office action) and Choi et al. (Proteomics 2010, 10, 72–80- cited and enclosed in the previous office action) as evidenced by MCE (Medchem express (https://www.medchemexpress.com/hsdvhk-nh2-tfa.html?srsltid=AfmBOoonapQKvQHSECmPs73rdOql1aLYN90gnqKWs_iriVlJOiVK6ZiV).
Anzali teaches a composition comprising an RGD cylic peptide (claims 4-6) and that the composition for treatment of psoriasis [0029, 0164, 0470, 0616, 0622] and as evidenced by Prignano, pruritus is an important symptom of psoriasis. Thus a treatment that is treating psoriasis is in turn also treating pruritus. Anzali teaches the peptide Cyclo-(Arg-Gly-Asp-DPhe-Aib) having an IC50 α2β3 integrins of 20nm (see [0589]). Anzali teaches that the cyclic peptides have integrin modulating properties, more preferably either integrin antagonistic activity, more preferably, the cyclic peptide use according to the invention ligands of integrins, selected from the group consisting of αvbeta3, αvβ5, αvβ1, αvβ6, αvβ8 and α2β3 integrins [0009].
Anzali does not teach the antagonists of integrin is disintegrin and that the antagonist comprises the RGD and SDV sequence as recited in claims 14 and 16.
Monleon teaches that Echistatin is a potent antagonist of the integrins αvβ3, α5β1 and αIIbβ3 and that its full inhibitory activity depends on an RGD (Arg-Gly-Asp) motif expressed at the tip of the integrin-binding loop and on its C-terminal tail (Abstract). Monleon further teaches RGD-containing disintegrins that show different binding affinity and selectivity towards integrins such as α2β3 integrins (Page 57, right col., 1st paragraph, line 12-16).
Choi teaches the hexapeptide P11 (HSDVHK) is a novel antagonistic peptide of integrin α2β3 and that P11 showed a strong antagonism against α2β3-GRGDSP interaction with an IC50 value of 25.72+/-73.34 nM (Abstract; Page 73, left col., 2nd paragraph, line 1-4). Examiner notes that as evidenced by MCE, the P11 peptide taught by Choi, P11 peptide has the sequence HSDVHK-NH2 (P11) (Page 2) which reads on the peptide of claim 17.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Anzali with the teachings of Monleon and Choi and use other integrin antagonists such as Echistatin, disintegrin and SDV peptides as taught by Monleon and Choi since both references teach that the antagonists showed a strong antagonism against α2β3 integrin (Page 57, right col., 1st paragraph, line 12-16). One of ordinary skill in the art would be motivated and would have had a reasonable expectation of success in using other antagonists of integrin α2β3 such as those taught by Monleon and Choi to treat conditions such as atopic dermatitis that have pruritus as a major symptom since Monleon teaches that Echistatin is a potent antagonist of the integrins αvβ3. The disclosures render obvious claims 14.
Regarding claim 15, Monleon teaches that Echistatin is a potent antagonist of the integrins αvβ3, α5β1 and αIIbβ3 and that its full inhibitory activity depends on an RGD (Arg-Gly-Asp) motif expressed at the tip of the integrin-binding loop and on its C-terminal tail (Abstract). Moleon further teaches RGD-containing disintegrins that show different binding affinity and selectivity towards integrins such as α2β3 integrins (Page 57, right col., 1st paragraph, line 12-16).
Regarding claims 16, Choi teaches the hexapeptide P11 (HSDVHK) is a novel antagonistic peptide of integrin α2β3 and that P11 showed a strong antagonism against α2β3-GRGDSP interaction with an IC50 value of 25.72+/-73.34 nM (Abstract; Page 73, left col., 2nd paragraph, line 1-4). It would have been obvious to one of ordinary skill in the art to use other antagonistic peptide of integrin α2β3 such as the one taught by Choi to treat pruritus associated with atopic dermatitis and psoriasis.
Regarding claim 17, Choi teaches the hexapeptide P11 (HSDVHK) is a novel antagonistic peptide of integrin α2β3 and that P11 showed a strong antagonism against α2β3-GRGDSP interaction with an IC50 value of 25.72+/-73.34 nM (Abstract; Page 73, left col., 2nd paragraph, line 1-4). It would have been obvious to one of ordinary skill in the art to use other antagonistic peptide of integrin α2β3 such as the one taught by Choi to treat pruritus associated with atopic dermatitis and psoriasis. Further, as evidenced by MCE, the P11 peptide taught by Choi, the P11 peptie has the sequence HSDVHK-NH2 (P11) (Page 2) which reads on the peptide of claim 17.
Regarding claim 20, Anzali teaches inhibitors of integrin αvβ3 known from clinical studies include the cyclic pentapeptide Cilengitide [0038]. Anzali teaches a composition comprising an RGD cyclic peptide (claims 4-6) and that the composition for treatment of psoriasis [0029, 0164, 0470, 0616, 0622] and as evidenced by Prignano, pruritus is an important symptom of psoriasis. Thus a treatment that is treating psoriasis is in turn also treating pruritus.
Regarding claim 21, Anzali teaches a composition comprising an RGD cyclic peptide (claims 4-6) and that the composition for treatment of psoriasis [0029, 0164, 0470, 0616, 0622] and as evidenced by Prignano, pruritus is an important symptom of psoriasis.
Regarding claim 22, claim 22 recites a result-oriented limitation. In this case, administering the same antagonist in claim 14 to the same subject would results in the same effect, as the one recited in claim 22.
Regarding claims 23-26, Anzali teaches inhibitors of integrin αvβ3 known from clinical studies include the cyclic pentapeptide Cilengitide [0038]. Anzali teaches a composition comprising an RGD cyclic peptide (claims 4-6) and that the composition for treatment of psoriasis [0029, 0164, 0470, 0616, 0622] and as evidenced by Prignano, pruritus is an important symptom of psoriasis. Prignano teaches that the treatment options for psoriasis and atopic dermatitis treat mild to severe itch (Page 9, last paragraph). Prignano teaches that the pruritus includes the severity of pruritus and frequency of pruritus such always which reads on chronic pruritus. It would have been obvious to use the peptide of Anzali to treat psoriasis and atopic dermatitis which is also known to alleviate chronic pruritus.
Claims 18-20 remain rejected under 35 U.S.C. 103 as being unpatentable over Anzali et al. (US 2011/0027209A1 – hereinafter “Anzali”- - cited and enclosed in the previous office action) as evidenced by Prignano et al. (Clin. Cosmet. Investig. Dermatol. 2009 Feb 19;2: 9–13-- cited and enclosed in the previous office action), in view of Celik et al. (WO 2017/088974A2 – hereinafter “Celik” - cited and enclosed in the previous office action), Goodman et al. (J. Med. Chem. 2002, 45, 1045-1051- cited and enclosed in the previous office action) and Morshed et al. (Molecules 2019, 24(8), 1537).
Anzali teaches a composition comprising an RGD cyclic peptide (claims 4-6) and that the composition for treatment of psoriasis [0029, 0164, 0470, 0616, 0622] and as evidenced by Prignano, pruritus is an important symptom of psoriasis. Thus a treatment that is treating psoriasis is in turn also treating pruritus. Anzali teaches the peptide Cyclo-(Arg-Gly-Asp-DPhe-Aib) having an IC50 α2β3 integrins of 20nm (see [0589]). Anzali teaches that the cyclic peptides have integrin modulating properties, more preferably either integrin antagonistic activity, more preferably, the cyclic peptide use according to the invention ligands of integrins, selected from the group consisting of αvbeta3, αvβ5, αvβ1, αvβ6, αvβ8 and α2β3 integrins [0009].
Anzali does not teach the antagonists of integrin α2β3 are peptidomimetics as recited in claim 18, and does not teach the antagonists are small molecules as recited in claims 19.
Celik teaches a method of treatment of fibrosis and/or fibrotic diseases comprising administering an anti-alpha-v integrin (receptor) antibody to patients for treating conditions including skin conditions (Abstract; claim 1-3), that the antibody includes DI17E6 (claims 1-3; Page 25, line 3-4 and line 10-11) and that the antibody has antagonistic activity on α2β3 integrins (Page 49, line 3-4; Page 50, line 15-16; page 55, line 18-29; page 57, line 15-17; page 61, line 27-28). Celik teaches a preferred antagonist of the invention is, however, cyclo-(Arg-Gly-Asp-DPhe-NMeVal) (Cilengitide) which is efficacious in blocking the integrin receptors αvβ5 and α2β3 (Page 56, line 1-5). Celik teaches that integrin (receptor) antagonists may be natural or synthetic peptides, non-peptides, peptidomimetics, immunoglobulins, such as antibodies or functional fragments thereof, or immunoconjugates (fusion proteins) and that preferred integrin inhibitors of the invention are directed to receptor of αvβ5 and α2β3 and that preferred integrin inhibitors are αv antagonists, and in particular α2β3 (Page 55, line 24-30).
Goodman teaches small molecules inhibitors of αvβ6, αvβ5, and αvβ3 integrins (Title; Abstract). Goodman teaches compounds such as compound 1 that comprises the RGD peptide (see 1047, top of page). Goodman teaches antagonist such as cyclic (-Arg-Gly-Asp- D -Phe-(NMe)Val-), EMD 121974 (compound 2), which is also known as Cilengitide and that the compound has an IC50 value of 3 nM on αvβ3 and 37nM on αvβ5 (Page 1046, right column, 2nd paragraph, line 1-20) and that the RGD sequences were in a form a peptidomimetics (Page 1046, left col. Last paragraph).
Further, Morshed teaches small molecule αvβ3 antagonist such cilengitide, and SB273005 (Page 14, 1st paragraph; Table 1). Examiner notes that the compound SB273005 is a small molecule compound. Further Morshed teaches SCH221153 is a RGD-based peptidomimetic αvβ3 and αvβ5 inhibitor (Page 8, 1st paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Anzali with the teachings of Celik and Goodman and use other integrin antagonists peptidomimetics as taught by Celik and Goodman and Morshed to treat pruritus in conditions such as atopic dermatitis since Celik teaches that antagonists such as Cilengitide is efficacious in blocking the integrin receptors αvβ5 and α2β3 (Page 56, line 1-5). One of ordinary skill in the art would be motivated and would have had a reasonable expectation of success in using other antagonists of integrin α2β3 such as those taught by Celik and Goodman to treat conditions such as atopic dermatitis that have pruritus as a major symptom since Goodman and Morshed teaches that such small molecules inhibitors of αvβ6, αvβ5, and αvβ3 integrins (Title; Abstract). The disclosures render obvious claim 18.
Regarding claim 19, Goodman teaches small molecules inhibitors of αvβ6, αvβ5, and αvβ3 integrins (Title; Abstract). Goodman teaches compounds such as compound 1 that comprises the RGD peptide (see 1047, top of page). Goodman teaches antagonist such as cyclic (-Arg-Gly-Asp- D -Phe-(NMe)Val-), EMD 121974 (compound 2), which is also known as Cilengitide and that the compound has an IC50 value of 3 nM on αvβ3 and 37nM on αvβ5 (Page, right column, 2nd paragraph, line 1-20) and that the RGD sequences were in a form a peptidomimetics (Page 1046, left col. Last paragraph). Further, Morshed teaches small molecule αvβ3 antagonist such cilengitide, SB273005 (Page 14, 1st paragraph; Table 1). Further Morshed teaches SCH221153 is a RGD-based peptidomimetic αvβ3 and αvβ5 inhibitor (Page 8, 1st paragraph). It would have been obvious to one of ordinary skill in the art to use other antagonists of integrins such as SB273005 as taught by Morshed to treat pruritus and would have achieved a reasonable expectation of success.
Regarding claim 20, Anzali teaches a composition comprising an RGD cylic peptide (claims 4-6) and that the composition for treatment of psoriasis [0029, 0164, 0470, 0616, 0622] and as evidenced by Prignano, pruritus is an important symptom of psoriasis. Thus a treatment that is treating psoriasis is in turn also treating pruritus. Anzali teaches the peptide Cyclo-(Arg-Gly-Asp-DPhe-Aib) having an IC50 α2β3 integrins of 20nm (see [0589]). Anzali teaches that the cyclic peptides have integrin modulating properties, more preferably either integrin antagonistic activity, more preferably, the cyclic peptide use according to the invention ligands of integrins, selected from the group consisting of αvbeta3, αvβ5, αvβ1, αvβ6, αvβ8 and α2β3 integrins [0009]. Anzali teaches inhibitors of integrin αvβ3 known from clinical studies include the cyclic pentapeptide Cilengitide [0038]. Further, Goodman teaches antagonist such as cyclic (-Arg-Gly-Asp- D -Phe-(NMe)Val-), EMD 121974 (compound 2), which is also known as Cilengitide and that the compound has an IC50 value of 3 nM on αvβ3 and 37nM on αvβ5 (Page, right column, 2nd paragraph, line 1-20) which indicates preference on αvβ3 integrin.
Response to Arguments
Applicant's arguments filed 03/17/2026 have been fully considered but they are not persuasive.
Applicant Arguments
Applicant argues that the teachings of the cited references at best pertain to the alleviation of inflammation, including in skin diseases, such as psoriasis and that the references are silent with regard to the alleviation of itch.
Applicant argues that the instant peptides target a neurogenic pathway rather than the immunological signaling driving inflammation and that blocking periostin-integrin neuronal signaling selectively targets the neurogenic pathway responsible for pruritus, but not inflammation.
Examiner’s Response
The arguments presented above have been fully considered but are unpersuasive.
Examiner notes that the primary reference teaches the instant compound for treating conditions such as psoriasis, skin atopy, eczema conditions that are characterized by severe pruritus or itchiness. Examiner notes that as evidenced by Prignano, pruritus is an important symptom of psoriasis. Thus a treatment that is treating psoriasis is in turn also treating pruritus. Further, Examiner cites Yarbrough et al. (Dermatol Ther. 2013 Mar-Apr;26(2):110–119) in an effort to rebut Applicant arguments. Yarbrough teaches several treatments of atopic dermatitis, eczema all of which are anti-inflammatory and treat severe itch or pruritus. Examiner notes that the instant invention recites a method of treating or alleviating pruritus, and the method of Anzali uses the instant peptide to treat conditions such as psoriasis, skin atopy, eczema, that are conditions that are characterized by severe pruritus or itchiness and the treatment of such conditions is known to alleviate itchiness or pruritus. Examiner notes that Applicant argument that the instant peptides target a neurogenic pathway rather than the immunological signaling driving inflammation is not persuasive because a simple discovery of another mechanism of action that leads to the same result (i.e. alleviating pruritus) is not new since the instant peptide is known to treat conditions which alleviate pruritus. Additionally, Examiner notes that Applicant has simply discovered an unappreciated property of a known method and "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. (See MPEP 2112 (I)).
Conclusion
No claims are allowed.
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 Mercy H. Sabila whose telephone number is (571)272-2562. The examiner can normally be reached Monday - Friday 5:00 am - 3:00 pm.
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/MERCY H SABILA/Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654
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