DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Election/Restrictions
Applicant’s election of species (i) SDF-1 of SEQ ID NO: 10, (ii) IL-2 of SEQ ID NO: 30, and (iii) avian infection bronchitis (IB) in the reply filed on 6/23/2026 is acknowledged. Applicants argue that upon allowance of claims to the elected species, the examination must be expanded to other species. This found to be persuasive if applicants provide the evidence that the other recited sequences for SDF1 (SEQ ID Nos: 12,14,16 or 18) and for IL-2 (SEQ ID NO: 32, 34, 36 or 38) are at least 95% identical and have the same functionality.
The requirement is still deemed proper and is therefore made FINAL.
Status of Application, Amendments, And/Or Claims
Claims 1-8 are pending and under examination to the extent they read on elected species.
Priority
The instant application is a DIV of US Application No. 16/415,143 filed on 5/17/2019 which was a DIV of US Application No. 15/658,929 filed on 7/25/2017, now US Pat. No. 10,336,801.
Information Disclosure Statement
The Information Disclosure Statement filed on 3/17/2023 has been considered.
Title
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. The title recites “A FUSION
PROTEON……….”. The following title, for example, is suggested: A method of ……...
Specification
Sequence Non-Compliance
The disclosure is objected to because of the following informalities: the disclosure is objected for reciting nucleotide and/or amino acid sequences which are not in the sequence compliance as per 37 CFR 1.821-1.825. The sequence rules embrace all unbranched nucleotide sequences with ten or more bases and all unbranched, non-D amino acid sequences with four or more amino acids, provided that there are at least 4 “specifically defined” nucleotides or amino acids. The rules apply to all sequences in a given application, whether claimed or not (see MPEP 2421.02). It should be noted, though, that when a sequence is presented in the disclosure (see page 7, 2nd paragraph), regardless of the format or the manner of presentation of that sequence in the claim, the sequence must still be included in the Sequence Listing and the sequence identifier (“SEQ ID NO:X”) must be used to refer the sequence.
Appropriate correction is required.
Sequence Non-Compliance
Claim Objections
Claims 1 and 5 are objected to because of the following informalities: Claims 1 and 5 recite nucleotide and/or amino acid sequences which are not in the sequence compliance as per 37 CFR 1.821-1.825. The sequence rules embrace all unbranched nucleotide sequences with ten or more bases and all unbranched, non-D amino acid sequences with four or more amino acids, provided that there are at least 4 “specifically defined” nucleotides or amino acids. The rules apply to all sequences in a given application, whether claimed or not (see MPEP 2421.02). It should be noted, though, that when a sequence is presented in claims 1 and 5, regardless of the format or the manner of presentation of that sequence in the claim, the sequence must still be included in the Sequence Listing and the sequence identifier (“SEQ ID NO:X”) must be used to refer the sequence.
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.
Claims 1-3, and 5 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 written description in this case only sets forth a method for promoting lymphocyte proliferation in a subject in need thereof comprising administering to the subject avian infectious bronchitis vaccine in combination with a fusion protein of stromal cell-derived factor-1 (SDF-1) and interleukin-2 (IL-2) as an adjuvant, or fusion protein comprising amino acid sequence of SEQ ID NO: 44, and therefore the written description is not commensurate in scope with “a method of promoting lymphocyte proliferation in a subject in need thereof comprising administering to the subject any vaccine in combination with a fusion protein of stromal cell-derived factor-1 (SDF-1) and interleukin-2 (IL-2) as an adjuvant, wherein the SDF-1 comprising amino acid sequence of SEQ ID NO: 10,12, 14,16 or 18, and the IL-2 comprises amino acid sequence of SEQ ID NO: 30, 32, 34, 36 or 38”.
The claims broadly encompass a method of promoting lymphocyte proliferation in a subject in need thereof comprising administering any vaccine in combination of a fusion protein comprising any SDF-1 having amino acid sequence of SEQ ID NO 12, 14, 16 or 18 and any IL-2 having amino acid sequence of SEQ ID NO: 32, 34, 36, or 38. The claims do not require that a the amino acid sequence of SEQ ID NO: 14, 16, or 18; or SEQ ID NO:32, 34, 36 or 38 possess any sequence homology with SEQ ID NO: 12 or SEQ ID NO: 30, respectively; or possess any particular feature or structure that may promote lymphocyte proliferation.
Galipeau et al. (IDS, 2005/0053579) teach an immune-therapy conjugate which comprises a formula A-c-B, wherein A and B are different and selected from the group consisting of cytokines, chemokines, interferons, their receptors, or a functional fragment thereof; c can be a linker (abstract, [0012-0015], for example). They teach that cytokine can be IL-2 and chemokine CXCL12 (SDF-1) (pg. 2, [0016-0017]). Therefore, the teach to make a fusion protein of IL-2 and SDF-1. They do not teach making a fusion of SDF-1 of SEQ ID NO: 10 and IL-2 of SEQ ID NO: 30. The specification at pg. 7 discloses to select chemokine sequence of SEQ ID NO: 2,4,6,….14, 16 or a homologue thereof and an analog thereof; and to select a cytokine from SEQ ID NO: 20, 22, 24, 226, 28, ….36 or 38, and a homolog and an analog thereof. However, the specification does not disclose amino acid sequence or a fragment thereof IL-2 and SDF-1 sequences necessary for the promotion of lymphocyte proliferation. The specification does not disclose any analog or derivative of amino acid sequence of SEQ ID NO: 10 or SEQ ID NO: 30. The general knowledge and level of skill in the art do not supplement the omitted description because specific, not general, guidance is what is needed.
Applications Under the 35 U.S.C. 112, 1 "Written Description" Requirement, Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001.
Vas-Cath Inc. V. Mahurka, 19 USPQ2d 1111, states that applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention, for purposes of the written description inquiry, is whatever is now claimed (see page 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (see Vas-Cath at page 1116).
Applications Under the 35 U.S.C. 112, 1 "Written Description" Requirement, Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001.
Vas-Cath Inc. V. Mahurka, 19 USPQ2d 1111, states that applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention, for purposes of the written description inquiry, is whatever is now claimed (see page 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (see Vas-Cath at page 1116). The conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of making a mutation. The compound itself is required. See Fiers v.Revel, 25USPQ2d 1601 at 1606 (CAFC 1993) and Amgen v.Baird, 30 Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 148 at 1483. In Fiddes, claims directed to mammalian FGF's were found to be unpatentable due to lack of written description for that broad class.
Therefore, only the method of promoting lymphocyte proliferation using a hybrid sequence of SEQ ID NO: 44 or a combination of amino acid sequence of SEQ ID NO:L 10 for SDF-1 and amino acid sequence of SEQ ID NO: 30 of IL-2 polypeptide, but not the full breadth of the claim meets the written description provision of 35 U.S.C. §112, first paragraph.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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 1-8 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Galipeau et al. (US 2005/0053579), Tan et al. (US 2003/0103938), Stebler et al. (IDS, Dev Biol. 2004, 272: 351-361) and Tsao et al (IDS, Q5US38_Chick, 12/7/2004, provided by applicants).
Galipeau et al. (IDS, 2005/0053579) teach an immune-therapy conjugate which comprises a formula A-c-B, wherein A and B are different and selected from the group consisting of cytokines, chemokines, interferons, their receptors, or a functional fragment thereof; c can be a linker (abstract, [0012-0015], for example). They teach that cytokine can be IL-2 and chemokine CXCL12 (SDF-1) (pg. 2, [0016-0017]). They do not teach that the linker comprises a peptide of sequence of (EAAAK)n, wherein n can be less than (1, for example).
Arai teaches design of the linkers for a bifunctional fusion protein, wherein the flexibility and hydrophilicity of the linker were important not to disturb the functions of the domains; and that simple linking of the two moieties by a flexible linker is not sufficient sometimes in retaining the functional activity (binding activity, as an example) of the fused protein, and the loss of the functional (binding) activity of could be envisaged due to some sort of interaction and interference between the two moieties (page 529, the paragraph bridging the two columns). Further, Arai teaches the linkers comprising a monomeric hydrophilic α-helix, such as A(EAAAK)nA (n=2-5) (for example, AEAAAKEAAAKEAAAKA (abstract, and page 529, 2ⁿᵈ column, 2ⁿᵈ paragraph), and the results indicating that the helical linkers can effectively separate the domains of fusion proteins and the distance between the domains can be controlled by changing the repetitions of the EAAAK motif, suggesting the potential of the helical linkers as
first candidates for its building block, especially for a multi-functional fusion protein (page 531, 2ⁿᵈ column, last paragraph).
Tan teaches a pharmaceutical composition comprising IL-2 and SDF-1α, which can be used for treating a Th2 cell-related disease (page 2, [0020] and [0022], for example).
Stebler teaches a chicken SDF-1 (accession number Q6T7C0_CHICK), which amino acid sequence is 100% identical to the present SEQ ID NO:10, wherein amino acids 1-21 represent the signal peptide of the SDF-1 (page 353, Fig. 1).
Tsai teaches a chicken IL-2 with the accession number Q5UB38, which amino acid sequence is 100% identical to the present SEQ ID NO:30, wherein amino acids 1-22 represent the signal peptide.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use an amino acid sequence of SDF-1 of SEQ ID NO: 10 as taught by Stebler, IL-2 of amino acid sequence of SEQ ID NO: 30 as taught by Tsai in a fusion protein as taught by Galipeau et al. Further, it would have been obvious to one skill in the art to use a linker having amino acid sequence (EAAAK)N as taught by Arai for promoting lymphocyte proliferation in a subject have T-cell related diseases as taught by Tan et al. Additionally, one would have been motivated to do so because Tan et al teach a pharmaceutical composition comprising IL-2 and SDF-1 for treating a disease in a subject in need thereof. Further, one would have a reasonable expectation of success in using SDF-1 (SEQ ID NO:10) and IL-2 (SEQ ID NO: 30) using a linker for promoting lymphocyte proliferation because it is routine to make a fusion protein from proteins or peptides of similar functionality. Therefore, the invention as whole would have been obvious to one ordinary skill in the art over the combined teachings of prior art.
Expected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof." See In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1967) (resultant decrease of dental enamel solubility accomplished by adding an acidic buffering agent to a fluoride containing dentifrice was expected based on the teaching of the prior art); Ex parte Blanc, 13 USPQ2d 1383 (Bd. Pat. App. & Inter. 1989); see also MPEP §716.02(c). Additionally, “[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.” See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) and MPEP § 2144.06.
Conclusion
No claim is allowed.
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/GYAN CHANDRA/Primary Examiner, Art Unit 1674
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