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 .
Restriction/Election
Applicant’s election without traverse of Group I, claims 29, 30, 33, and 94-103 in the reply filed on 05/13/25 is acknowledged.
Claims 104-110 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/13/25. Claims 33 and 94-101 were previously searched. However, upon amendment, independent claims 29 now requires that the positions recited correspond to the native human TFF2 polypeptide, which is either SEQ ID NO: 1 (unprocessed human TFF2) or SEQ ID NO: 6 (mature human TFF2), as defined in the specification. This will be addressed in a new grounds of rejection below.
Additionally, amended claims 33 and 94 were reviewed, and art was found that reads on both, as they are taught as separate binding domain fragments. Because of the art rejection over claims 33 and 94, which could have been made over previous dependent claims 33 and 94, this is a second Non-final rejection.
For the purpose of compact prosecution, please note that the rejection over claims 33 and 94 includes the only art found that reads on these claims. The rejection over claim 29 does not represent the full scope of the art found, as the new grounds of rejection over 112(B) will address the clarity of the claimed sequence positions.
New claims 111-119 were added. Claims 29, 30, 33, 94-97 and 99-119 are pending. Claims 104-110 remain withdrawn. Claims 29, 30, 33, 94-97, 99-103 and 111-119 are under examination. An Office action on the merits that follows.
Allowable Subject Matter
Claims 97, 113, 116, and 119 were searched and found to be free of the art. As such, the claims are in condition for allowance because claim 97 was amended to an independent claim.
Objections
Claims 95, 96 and 99-101 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Rejections 35 USC 112 (B)
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.
Claims 29, 30, 102 and 103 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. The claims recite “A TFF2 polypeptide,” and designates it as “native human,” with specified positions of which at least one must be substituted. However, it is not clear from the claims which positions of which sequences the claims correspond to. The recited positions are Phe21, Thr25, Asp27, Gln28, Asn32, Tyr70, Ser74, Glu77 and Arg81, but the claims do not state whether the native human TFF2 should refer to SEQ ID NO: 1 (unprocessed human TFF2) or SEQ ID NO: 6 (mature human TFF2). Clarification regarding the corresponding sequence is required.
Claim Rejections 35 USC 102(A)
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 29, 30, 102 and 103 are rejected under 35 U.S.C. 102(A) as being anticipated by Lobie (US 2009/022708).
Lobie teaches a chimera/ fusion protein of a whole or fragment or mutant of the TFF of fused with another protein of interest, such as human serum albumin [0010-0014 and FIG. 13]. This reference further teaches TFF2 variants, in which the residues located at corresponding residues in the structure of TFF2 are substituted with a non-identical amino acids, relative to the wild type sequence [0010]. This reference specifically teaches TFF2a mutants comprising a non-identical amino acid at positions 21, 22, 43, and/or 44 of SEQ ID NO: 37 (TFF2a) and TFF2 mutants, comprising a non-identical amino acid at positions 70, 71, 92, 93, and/or 103 of SEQ ID NO: 37 (TFF2b) [0014]. Lobie teaches that these mutant TFF polypeptides are the same length or shorter than the corresponding wild type full length molecule, and are optionally linked, (i.e., conjugated to), or recombinantly produced as a chimeric or heterologous polypeptides with other proteins, such as human serum albumin (HSA) [0014, 0168].
This meets the limitations of claims 29 and 30 by teaching HSA fused to TFF2 polypeptides. Because the positions of the peptide are not specified with a claimed sequence, this claim can be interpreted broadly to include the polypeptide of the prior art, SEQ ID NO: 37, which is shifted by the deletion of Glutamic acid at position 1 of SEQ ID NO: 6 in the instant sequence listing. As such, the prior art teaches a TFF2 polypeptide that is substituted at each of the claimed positions, absent further clarification in the claims. Claim 102 is met because Lobie teaches that these fusion proteins may be conjugated to PEG to increase half-life [0143, 0168]. Claim 103 is met because this reference teaches the TFF2-HSA proteins in pharmaceutical compositions with a carrier [0016].
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.
Claim(s) 29, 30, 33, 94, 102, 103, 111, 112, 114, 115, 117 and 118 is/are rejected under 35 U.S.C. 103 as being unpatentable over Podolsky (US7,538,082) in view of Lobie (US2009/022708).
Podolsky teaches that human trefoil peptides are any polypeptide having at least a “trefoil domain,” and retaining a biological activity characteristic of the trefoil domain and comprises a polypeptide having a sequence substantially identical to any one of SEQ ID NOs: 7-10 (Col. 2, lines 25-60). This reference further teaches that such peptides correspond to the trefoil domains of hSP130-71 (TFF-2, domain I), corresponding to SEQ ID NO: 8 of Podolsky and instantly claimed SEQ ID NO: 24. This reference also teaches hSP280-120 (TFF2 binding domain II), corresponding to SEQ ID NO: 9 of Podolsky and instantly claimed SEQ ID NO: 25.
This reference also teaches that TFF2 polypeptides are sequences of four identified human trefoil domains, as follows:
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206
842
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(Col. 2, lines 45-60; Fig. 4).
Although this reference does not specifically teach that each domain is a separate pharmaceutical formulation, and used as functional fragments, Podolsky teaches that it is recognized in the art that the six conserved cysteine residues of these sequences impart the characteristic three-loop (trefoil) structure to the protein, and that the loop structure conforms to the general intrachain disulfide configuration of Cys1-5, (corresponding to amino acid residues 25 and 51 of hITF; SEQ ID NO.:1 of Podolsky), Cys2-4 (corresponding to amino acid residues 35 and 50 of hITF; SEQ ID NO: 1) and Cys3-6 (corresponding to amino acid residues 45 and 62 of hITF, SEQ ID NO.:1).
Additionally, Podolsky teaches Pharmaceutically acceptable carriers (spanning Col. 1-2).
The difference between the prior art teachings and the instant claims is that the prior art does not teach conjugating these binding domain fragments to an albumin fusion protein.
However, as discussed above, Lobie teaches a chimera/fusion protein of a whole or fragment or mutant of the TFF2, fused with another protein of interest, such as human serum albumin [0010-0014 and FIG. 13]. This reference further teaches TFF2 variants, in which the residues located at corresponding residues in the structure of TFF2 are substituted with a non-identical amino acid relative to the wild type sequence [0010]. Lobie teaches that these mutant TFF polypeptides are the same length or shorter than the corresponding wild type full length molecule and are optionally linked (e.g., conjugated to or produced as a recombinant chimeric protein) to a heterologous polypeptide such as HSA [0014, 0168].
Lobie also teaches that peptide antagonists include fragments of the native TFF2 protein fused to a heterologous peptide, such as HSA, which serve to increase serum half-life (i.e., decrease protein degradation), decrease rapid excretion of the construct by the kidneys and impair action with TFF and it receptor activation [0135].
As such, it would have been obvious to one of ordinary skill in the art at the filing date of the invention to have taken the TFF2 peptide fragments of Podolsky and conjugated them to the HSA of Lobie because Podolsky teaches that these fragments have the necessary binding functions of TFF2, which require the cysteine configuration present in human TFF2 binding domains I and II. One would be motivated to conjugate HSA of Lobie to the TFF2 fragments of Podolsky because Lobie teaches that HSA increases half-life, decreases rapid kidney excretion and decreases receptor activation. Therefore, there is a reasonable expectation of success that the peptides of Podolsky will be effective when conjugated to the HSA of Lobie to improve these properties.
This meets the limitations of claims 33, 94, 111 and 112 because Podolsky teaches functional TFF2 fragments, comprising binding domain I or binding domain II, and Lobie provides motivation to conjugate them to HSA. Claims 114 and 115 are met because Lobie teaches that these fusion proteins may be conjugated to PEG to increase half-life [0143, 0168].Claims 117 and 118 are met because both references teach pharmaceutical carriers. Claims 29, 30, 102 and 103 are met by Lobie for the reasons discussed above in the 102 rejection.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANETTE M LIEB whose telephone number is (571)270-3490. The examiner can normally be reached M-F 10-7.
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/JEANETTE M LIEB/Primary Examiner, Art Unit 1654