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 .
DETAILED ACTION
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 1-17 have an effective filing date of 17 MAY 2022.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 10/17/2023 & 09/07/2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Election/Restriction
In the response filed on 1/2/2026, Applicant elected, without traverse:
Group I, claims 1-12
Status of Claims
Claims 1-17 are currently pending and presented for examination on the merits.
Claims 13-17 are withdrawn from further consideration by Examiner under 37 CFR 1.142(b) as being drawn to a non-elected species.
Claim Rejections - 35 USC § 112
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 1-12 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.
Claim 1 is rejected. Claim 1, line 2, recites “one or more modifications”. The specifications states that modifications that may be present may vary, and include but are not limited to: amide bond substitutions, amino acid substitutions, including of cysteine residues/analogues, cyclization, pegylation, etc. [Page 17 of Specifications]. It is unclear what the metes-and-bounds of modification entails. Clarification is required.
Claim 4 is rejected. Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The term “Fe region” in claim 4 is used by the claim to mean “Fc region.” The term is indefinite because the specification does not clearly redefine the term.
Claim 5 is rejected. Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The term “Fe region” in claim 5 is used by the claim to mean “Fc region.” The term is indefinite because the specification does not clearly redefine the term.
Claim 5 is rejected. Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The term “h1gG4” in claim 5 is used by the claim to mean “hIgG4.” The term is indefinite because the specification does not clearly redefine the term.
Claim Rejections - 35 USC § 102
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
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.
Claim 1 is rejected under 35 U.S.C. 102(a)(2) as being anticipated by Wyss-Coray et al (US 20200254075 A1, IDS 10/17/2023).
In regard to claim 1, Wyss-Coray et al teaches TIMP-2 polypeptides that include one or more modifications [0036]. Wyss-Coray et al further teaches modifications include but are not limited to: amide bond substitutions, amino acid substitutions, including of cysteine residues/analogues, cyclization, pegylation, etc [0036].
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.
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 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 1-8, and 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Wyss-Coray et al (US 20200254075 A1, IDS 10/17/2023) as applied to claim 1 above, and further in view of Zhang et al (Alteration in the IL-2 signal peptide affects secretion of proteins in vitro and in vivo, J Gene Med 2005; 7: 354–365, IDS 10/17/2023).
The teachings of Wyss-Coray et al are discussed above.
Wyss-Coray et al does not specifically teach modifications to the signaling protein. However, this deficiency is made up in the teachings of Zhang et al.
In regards to claim 2, Zhang et al teaches the modification of the signal peptide [Abstract]. Zhang et al further teaches the modification are to increase therapeutic levels of secreted proteins [Abstract].
One of ordinary skill, before the effective filing date, would have been motivated to combine Wyss-Coray’s method of modifying TIMP-2 polypeptide, with Zhang’s method of modifying the signaling protein to one that is not present in the native protein. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine Wyss-Coray and Zhang’s methods for a recombinant TIMP-2 protein comprising a signal peptide not present in native human TIMP-2, because Zhang teaches the modification of the signal peptide to modify the production of protein products.
In regards to claim 3, Zhang et al further teaches a signal protein from IL-2 for cells MDA-MB-435 [Abstract]. Zhang further teaches both modified and wild-type signal peptide [Abstract].
In regard to claim 4, Wyss-Coray et al further teaches the addition of a Fc region [0056].
In regards to claim 5, Wyss-Coray et al further teaches attaching an Fc region to the polypeptide [0056]. Wyss-Coray et al further teaches an Fc attachment has been shown to increase the systemic half-life of bio-pharmaceuticals [0056]. Furthermore, one of ordinary skill in the art would have been motivated to modify the Fc region [0056], and one of ordinary skill in the art would appreciate that there are four IgG subclasses, IgG1-IgG4.
In regards to claim 6, Wyss-Coray et al further teaches the TIMP-2 polypeptide also includes fragments thereof which exhibits the desired TIMP-2 activity [0031].
In regards to claims 7-8, Wyss-Coray et al further teaches variations from the TIMP polypeptides, including amino acid insertions [0035].
In regards to claim 11, Wyss-Coray et al further teaches the use of nucleic acid encoding the protein to be produced in cells [0051].
In regards to claim 12, Wyss-Coray et al further teaches the use of nucleic acids in vectors [0063].
Claims 1-12 are rejected under 35 U.S.C. 103 as being unpatentable over Wyss-Coray et al (US 20200254075 A1, IDS 10/17/2023), Zhang et al (Alteration in the IL-2 signal peptide affects secretion of proteins in vitro and in vivo, J Gene Med 2005; 7: 354–365, IDS 10/17/2023) as applied to claims 1-8, and 11-12 above, and further in view of Higashi et al (US 20110195902 A1).
The teachings of Wyss-Coray et l and Zhang et al are discussed above.
Wyss-Coray et al and Zhang et al do not specifically teach the insertion of alanine before amino acid 27 of the native human TIMP-2 sequence. However, this deficiency is made up by Higashi et al.
In regard to claims 9-10, Higashi et al teaches coordination of the α-amino group of the N-terminal Cys 1 of TIMP-2 to the zinc ion at the activity center of MMP is important for the inhibitory activity of TIMP-2; when this α-amino group is chemically modified, or when one alanine residue is added to the N-terminus of TIMP-2 (see [0095]), the result is an MMP-2 inhibitor - “when APP-IP is added to the N-terminus of TIMP-2, TIMP-2's MMP inhibitory activity with low specificity is lost and, at the same time, interaction between APP-IP and the catalytic site of MMP-2 is enhanced, yielding an inhibitor with high affinity and specificity for MMP-2.”
One of ordinary skill, before the effective filing date, would have been motivated to combine Wyss-Coray’s method of modifying TIMP-2 polypeptide, with Zhang’s method of modifying the signaling protein to one that is not present in the native protein, with Higashi’s method of adding an alanine to the N-terminus of TIMP-2. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine Wyss-Coray, Zhang, and Higashi’s methods for a recombinant TIMP-2 protein comprising a signal peptide not present in native human TIMP-2 and inserting an alanine in to the N-terminus, because the result is an MMP-2 inhibitor. This would be an advantageous modification, because “[m]atrix metalloproteinases (MMPs) are proteolytic enzymes having high degradation activity against extracellular matrix proteins and are considered to support cell migration during cancer invasion and metastasis.” See [0002].
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DENNIS JOHN SULLIVAN whose telephone number is (571)272-0509. The examiner can normally be reached Mon - Fri: 7:30AM - 4:30PM.
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/DENNIS J SULLIVAN/Examiner, Art Unit 1642
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642