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 .
Claim Status
Claims 1-6 are pending.
Claims 1-6 have been examined.
Priority
This application is a 371 of PCT/KR2022/004434 filed on 03/29/2022, which claims foreign priority of KOREA, REPUBLIC OF 10-2021-0078174 filed on 06/16/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/12/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Claim Objections
Claims 2-3 are objected to because of the following informalities:
Claim 2 contains the acronyms of CCL17, CCL22, KDM6B, GMCSF, TSLP, and IL-31, and an acronym in the first instance of claims should be expanded upon/spelled out as “C-C motif chemokine ligand 17”, “C-C motif chemokine ligand 22”, “lysine-specific demethylase 6B”, “granulocyte-macrophage colony-stimulating factor”, “thymic stromal lymphopoietin”, and “Interleukin-31” with the acronym indicated in parentheses as (CCL17), (CCL22), (KDM6B), (GMCSF), (TSLP), and (IL-31) respectively. The abbreviations can be used thereafter.
Similarly, the acronyms of JAK2 and STAT1 in claim 3 should be expanded upon/spelled out as “Janus kinase 2 (JAK2)” and “signal transducer and activator of transcription 1 (STAT1)”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Written Description Rejection
Claims 1-6 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The specification failed to provide a representative number of a polypeptide comprising the tetrapeptide of KTFR.
The specification disclosed hydrolyzing a synthetic unknown polypeptide sequence with 6N-HCl [52] and a tetrapeptide sequence KTFR (SEQ ID NO: 1) is determined based on molecular weight [53-54]. Th limited disclosure of SEQ ID NO: 1 within an unknown polypeptide sequence is insufficient to represent the entire genus of any polypeptide comprising SEQ ID NO: 1 as claimed. However, the specification lacked written description to explain how the specific tetrapeptide sequence of KTFR was determined by molecular weight to rule out other tetrapeptide sequences with the same molecular weight such as TFRK, FRKT, RFTK, etc (the same 4 amino acid residues in any order).
The specification failed to correlation of structure and function of the peptides.
The specification disclosed hydrolyzing a synthetic unknown polypeptide sequence with 6N-HCl [52] and a tetrapeptide sequence KTFR (SEQ ID NO: 1) is determined based on molecular weight [53-54]. Since applicant failed to provide the synthesized polypeptide sequence before hydrolysis in the specification, the molecular weight of a tetrapeptide KTFR is the same for any tetrapeptide comprising the same 4 amino acid residues in any order such as TFRK, FRKT, RFTK, etc. The tetrapeptides with the same molecular weight do not share a structural similarity with the claimed KTFR. In particular, the specification lacks written description how the tetrapeptide sequence of KTFR was determined by molecular weight to rule out other tetrapeptide sequences with the same molecular weight.
Furthermore, a prior art reference of Krampert et al. (J Biol. 2005 Jun 24;280(25):23844-52, cited in IDS) teaches metalloproteinase ADAMTS1 (GeneBank: AAF 15317.1 as follows) as a potent inhibitor of angiogenesis (p23844, col 2, line 17-18) comprising the tetrapeptide KTFR with a distinct protein folding structure compared to applicant’s unknown polypeptide sequence
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or the tetrapeptide of KTFR.
Thus, the specification failed to establish a correlation of structure and function for the entire genus of a polypeptide comprising KTFR as claimed.
Claims 2-6 are further rejected as depending on claim 1.
The rejection may be overcome by explicitly claim the peptide sequence consisting of SEQ ID NO: 1.
Lack of full-scope Enablement Rejection
Claims 1-6 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating or alleviating inflammatory skin diseases, does not reasonably provide enablement for preventing inflammatory skin diseases. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims. Wands factors analysis is in the following.
(A) The breadth of the claims is much broader than support of the enabled examples.
(B) The nature of the invention is a peptide consisting of KTFR made from an unknown polypeptide sequence hydrolyzed in 6N HCl [52-54].
(C) The state of the prior art of Krampert et al. (J Biol. 2005 Jun 24;280(25):23844-52, cited in IDS) teaches a protein comprising KTFR as an inhibitor of angiogenesis (p23844, col 2, line 17-18).
(D) The level of one of ordinary skill is low because one of ordinary skill does not at once envisage to know which polypeptides comprising KTFR are able to treat inflammatory skin diseases and which polypeptides are not.
(E) The level of predictability in the art is low. Even though a polypeptide comprises KTFR, the polypeptide may or may not be able to treat inflammatory skin diseases.
(F) The amount of direction provided by the inventor is limited. The specification disclosed a peptide consisting of KTFR made from an unknown polypeptide sequence hydrolyzed in 6N HCl [52-54]. The specification disclosed a peptide consisting of KTFR used as a transcription inhibitor [25].
(G) The existence of working examples are insufficient to support the full scope of enablement. The specification disclosed a peptide consisting of KTFR used as a transcription inhibitor [25]. However, there is no actual example to show administration of a polypeptide comprising KTFR able to treat contact dermatitis, allergic dermatitis, systemic lupus erythematosus, seborrheic dermatitis, psoriasis, and atopic dermatitis to support the claim scope.
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure is unknown because The specification merely disclosed a peptide consisting of KTFR made from an unknown polypeptide sequence hydrolyzed in 6N HCl [52-54]. Thus, The quantity of experimentation needed to identify all polypeptides comprising KTFR to support the entire genus of polypeptides able to treat inflammatory skin diseases is unknown.
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.
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.
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.
1. Claims 1 and 4-6 are rejected under 35 U.S.C. 103 as being unpatentable over Krampert et al. (J Biol. 2005 Jun 24;280(25):23844-52, cited in IDS) in view of GeneBank: AAF 15317.1 (https://www.ncbi.nlm.nih.gov/protein/AAF15317.1, 06-DEC-1999) and Richarz et al. (Actas Dermosifiliogr. 2017;108(6):515-523).
Claim 1 is drawn to a method of treating inflammatory skin diseases comprising administering a composition comprising the tetrapeptide of KTFR (SEQ ID NO: 1).
Krampert et al. teach metalloproteinase SADAMT1 is a potent inhibitor of angiogenesis (p23844, col 2, line 17-18). GeneBank: AAF 15317.1 is cited to show SADAMT1 comprising the tetrapeptide of KTFR (see protein sequence at page 4 above).
Krampert et al. teach administration of SADAMT1 to treat wounded skin (Title), but do not specify administration of an angiogenesis inhibitor to treat an inflammatory skin disease.
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Richarz et al. teach most inflammatory and neoplastic diseases in dermatology are characterized by excessive angiogenesis, such as psoriasis, atopic dermatitis (Abstract). Because (a) Krampert et al. teach metalloproteinase SADAMT1 is a potent inhibitor of angiogenesis (p23844, col 2, line 17-18) and (b) Richarz et al. teach most inflammatory and neoplastic diseases in dermatology are characterized by excessive angiogenesis, such as psoriasis, atopic dermatitis (Abstract), one of ordinary skill in the art would have found it obvious to administer Krampert’s angiogenesis inhibitor of SADAMT1 comprising the tetrapeptide of KTFR (SEQ ID NO: 1) to treat an inflammatory skin disease of psoriasis and/or atopic dermatitis shown in the mechanism as follows (p517, Fig. 1), reading on claims 1 and 4-5.
One or ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine (i) Krampert et al. in view of GeneBank: AAF 15317.1 and (ii) Richarz et al. because (a) Krampert et al. teach metalloproteinase SADAMT1 is a potent inhibitor of angiogenesis (p23844, col 2, line 17-18) and (b) Richarz et al. teach most inflammatory and neoplastic diseases in dermatology are characterized by excessive angiogenesis, such as psoriasis, atopic dermatitis (Abstract). The combination would have reasonable expectation of success because both Krampert et al. and Richarz et al. teach angiogenesis inhibitors. GeneBank: AAF 15317.1 is cited to show Krampert’s metalloproteinase SADAMT1 comprising the tetrapeptide KTFR.
With respect to claim 6, Krampert et al. show SADAMT1 formulated in a solution at various concentrations for cell-based assays (p23850, Fig 7A).
2. Claims 1, 2-3, and 4-6 are rejected under 35 U.S.C. 103 as being unpatentable over Krampert et al. in view of GeneBank: AAF 15317.1 and Richarz et al. as applied to claims 1, 4-6, and further in view of Valdembri et al. (FASEB J. 2002 Feb;16(2):225-7).
Claim 2 is drawn to the peptide suppresses CCLI 7, CCL22, KDM6B, GMCSF, TSLP, and IL-31. Claim 3 is drawn to the peptide inhibits phosphorylation of JAK2 or STAT1.
Krampert et al. in view of GeneBank: AAF 15317.1 and Richarz et al. teach administration of a polypeptide comprising KTFR (SEQ ID NO: 1) to treat angiogenesis-mediated pathogenesis of psoriasis (p517, Fig 1).
Krampert et al. in view of GeneBank: AAF 15317.1 and Richarz et al. do not specify the angiogenesis inhibitor polypeptide further suppresses CCLI 7, CCL22, KDM6B, GMCSF, TSLP, and IL-31.
Valdembri et al. teach “In vivo activation of JAK2/STAT-3 pathway during angiogenesis induced by GM-CSF” (Title). Valdembri et al. teach GM-CSF induces the JAK-2-dependent tyrosine phosphorylation of STAT-1 (p2, para 1). Valdembri et al. teach subnanomolar concentrations of GM-CSF elicit JAK-2 tyrosine phosphorylation in cultured human endothelial cell (EC), as well as activation of its catalytic activity (p2, para 3). Because (a) Krampert et al. in view of GeneBank: AAF 15317.1 and Richarz et al. teach administration of an angiogenesis inhibitor to inhibit pathogenesis of psoriasis and endothelial cell proliferation (Richarz et al. p517, Fig 1), (b) Valdembri et al. teach GM-CSF inducing angiogenesis of endothelial cells (Abstract), and (c) Valdembri et al. teach GM-CSF induces the JAK-2-dependent tyrosine phosphorylation of STAT-1 (p2, para 1), one of ordinary skill in the art would have found it obvious to administer a polypeptide comprising KTFR (SEQ ID NO: 1) to treat GMCSF-mediated angiogenesis of an inflammatory skin disease (e.g., psoriasis) and one or ordinary skill in the art would expect inhibition of GMCSF-mediated angiogenesis would be able to inhibit (a) angiogenesis-mediated pathogenesis of psoriasis as well as (b) to inhibit GMCSF induction of the JAK-2-dependent tyrosine phosphorylation of STAT-1, reading on claims 2-3.
One of ordinary skill in the art before the effective filing sate of this invention would have found it obvious to combine (i) Krampert et al. in view of GeneBank: AAF 15317.1 and Richarz et al. and (ii) Valdembri et al. because (a) Krampert et al. in view of GeneBank: AAF 15317.1 and Richarz et al. teach administration of an angiogenesis inhibitor to inhibit pathogenesis of psoriasis and endothelial cell proliferation (Richarz et al. p517, Fig 1) and (b) Valdembri et al. teach GM-CSF inducing angiogenesis of endothelial cells (Abstract) and GM-CSF induces the JAK-2-dependent tyrosine phosphorylation of STAT-1 (p2, para 1). The combination would have reasonable expectation of success because both Richarz et al. and Valdembri et al. teach angiogenesis and endothelial cells.
Conclusion
No claim is allowed.
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/J.L/Examiner, Art Unit 1658
25-July-2026
/Melissa L Fisher/ Supervisory Patent Examiner, Art Unit 1658
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