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 .
Election/Restrictions
Applicant’s election without traverse of Group I, drawn to a composition comprising a hydrogel and one or more proteins non-covalently bound to one or more affibodies in the reply filed on 01/07/2026 is acknowledged. Applicant further elects VEGF as the protein species and SEQ ID NO: 20 as the affibody species. The elected VEGF affibody appears to be free of the prior art and thus the search was expanded to include all VEGF affibodies recited in the claims particularly SEQ ID NOs: 21-41, which also appear to be free of the prior art.
Claims 5 and 12-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/07/2026.
Claims 1-4 and 6-11 are examined on the merits in the present Office Action.
Claim Interpretation
The independent claim recites a composition comprising a hydrogel; one or more proteins; and one or more affibodies, wherein the one or more affibodies are specific for the one or more proteins. In view of applicant’s election of a single protein species (i.e. VEGF -not two or three different targets), the claim is interpreted as encompassing one or more affibodies that specifically bind to the same elected target VEGF. The dependent claims are examined consistent with this interpretation. For example, claim 6 is interpreted as a hydrogel comprising two different affibodies that target VEGF. However, the limitation “one or more affibodies” in combination with “one or more proteins” is, on its face, indefinite as it is unclear if the affibodies present in the hydrogel bind to the same target or to different targets. The dependent claims raise a similar issue under 35 USC 112(b) (see below).
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 1-4 and 6-11 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 independent claim recites a composition comprising a hydrogel; one or more proteins; and one or more affibodies, wherein the one or more affibodies are specific for the one or more proteins. The scope of the claim is unclear because it is ambiguous how the affibodies in the hydrogel correspond to the proteins. Specifically, it is unclear whether the hydrogel comprises
one or more affibodies specific for a single protein; or
multiple affibodies each specific for a different protein.
The claim language does not specify whether all affibodies must bind the same protein or whether different affibodies may bind different proteins. As a result, the metes and bounds of the desired patent prosecution desired cannot be determined.
Similarly, dependent claims 2, 4, 6-9, and 11 do not resolve this ambiguity as it remains unclear whether recited affibodies are specific for a single protein or whether multiple affibodies are specific for different respective proteins. Claims 3 and 10 (both dependent on claim 1) are rejected because they also do not cure the deficiencies of claim 1.
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)(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.
Claims 1-4 and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bostock (Bostock, Chiara. Design of an Affibody-Modified Hydrogel for the Controlled Release of FGF2. MS thesis. University of Toronto (Canada), 2021).
Bostock discloses an affibody modified hyaluronan (HA)-based hydrogel as a delivery vehicle for a growth factor, specifically fibroblast growth factor 2 (FGF2), thus providing a versatile delivery platform amenable to any protein with the potential for distinct multi-species release profiles based on specific affinity interactions. In particular, a highly specific affibody binding partner with an intermediate affinity (3.8 x 10-8 M) for FGF2 using yeast surface display. Controlled release of FGF2 from the hydrogel vehicle by was achieved by modulating the affibody to protein ratio and showed a stabilizing effect of the affibody on FGF2 (Abstract). The hydrogel is prepared as a pre-gel solution and is designed for injectability (2.2.16.3 Injectability); as such, the hydrogel is necessarily prepared with a pharmaceutically acceptable carrier.
Thus, Bostock meets the limitations of instant claims 1-4 and 10.
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.
Claims 1-4, 6, 7, 10, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Cao et al (US20150283210A1), hereinafter Cao, in view of Pakulska et al (Pakulska, Malgosia M., Shane Miersch, and Molly S. Shoichet. "Designer protein delivery: From natural to engineered affinity-controlled release systems." Science 351.6279 (2016): aac4750).
Cao teaches a scaffold comprising a biocompatible polymer matrix in which one or more bioactive substances are incorporated (Abstract, Summary of Invention: Para. 0005, 0007-0008, 0012), wherein the matrix is a hydrogel (Para. 0109). The bioactive substances include those that influence growth, development, movement, and other cellular functions: for example, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF-2), granulocyte macrophage colony stimulating factor (GM-CSF), monocyte chemotactic protein (MCP), and bone morphogenetic protein (BMP-2) among others (Para. 0128-0130). Bioactive substances are non-covalently linked to the scaffold (Para. 0011). The scaffold is designed to temporally control the release of the bioactive substances, enabling sustained delivery over time (Para. 0020 and 0040). The release profiles of bioactive substances from scaffold devices are controlled by both factor diffusion and polymer degradation, the dose of the factor loaded in the system, and the composition of the polymer (Para. 0069). The hydrogel matrix can be formed from natural or synthetic polymers, including materials such as collagen, gelatin, and hyaluronic acid (Para. 0109-0110). In an example, injectable alginate hydrogels incorporating VEGF are injected into a hindlimb ischemia site created by femoral artery and vein ligation in a murine model (Example 4). The hydrogels are thus necessarily administered to a subject with a pharmaceutically acceptable carrier.
Cao does not teach that the hydrogel scaffold is modified with one or more affinity ligands such as affibodies having different dissociation constants for the target bioactive substances such as VEGF.
However, Pakulska teaches that affinity-controlled release systems rely on reversible, non-covalent interactions between a therapeutic protein and an immobilized binding partner within a polymer matrix to modulate release of said protein. In such systems, the rate of diffusive release is governed factors including the binding affinity (Kd), binding kinetics (kon and koff), and the concentration of the binding ligand rather than degradation of the polymer matrix (Abstract and Figure 2). By selecting binding ligands with different affinities and covalently linking them to a hydrogel matrix, the release profile of the therapeutic protein can be tuned and precisely controlled (see “Discovery of binding ligands for affinity-controlled release” figure caption on Page 1279). Affibodies which bind a specific target are contemplated as suitable for affinity-controlled release and can be obtained with in vitro selection combined with diversification steps (e.g. random mutagenesis) (see Figure 1). This affinity-based approach provides advantages over a polymer matrix alone, including avoidance of harsh processing conditions such as organic solvents and high shear force typically used for protein encapsulation in water-insoluble polymers but which can cause protein instability and loss of function. Thus, the affinity-based approach enables higher loading of active therapeutics (see Abstract on Page 4750-1 and first paragraph under “Future outlook on affinity-controlled release” on page aac4750-6).
It would have been obvious to one of ordinary skill in the art to modify the hydrogel scaffold of Cao to include affinity ligands, such as affibodies that bind to the bioactive substances (e.g. VEGF). One of ordinary skill in the art would have been motivated to do so to achieve affinity-controlled delivery of therapeutic proteins (in this case, growth factors such as VEGF). Hydrogel-based scaffolds can be used for delivery of pro-angiogenic factors such as VEGF but rely on the properties of the polymer matrix to control release as taught by Cao, such as polymer degradation. In contrast, incorporation of immobilized binding ligands with different binding affinities into a hydrogel provides an additional level of control over the release of therapeutic proteins while avoiding harsh processing conditions such as organic solvents and high shear force typically used for protein encapsulation in water-insoluble polymers as taught by Pakuluska. Further, "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); thus, it would have been prima facie obvious to one of ordinary skill in the art to determine by routine experimentation the optimum number of affibodies (one, two, three, or more) present in the hydrogel as well as dissociation constants of each affibody in order to improve controlled release of the bioactive substance such as VEGF. Therefore, one of ordinary skill in the art would have reasonably expected a hydrogel modified with affibodies that target one or more bioactive substances such as VEGF at different dissociation constants can be used to effectively control the delivery of said bioactive substances to a subject.
Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 1-4, 6, 10, and 11 are provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 1-4, 6, 9, and 10 of copending Application No. 19238192 (reference application), respectively. This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented. The co-pending claims are identical in wording and in scope to the instant claims 1-4, 6, 10, and 11.
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 7, 8 and 9 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of copending Application No. 19238192 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the co-pending claims either anticipate or are obvious variants over the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The co-pending claims recite a composition comprising a hydrogel; one or more proteins; and one or more affibodies specific for the one or more proteins. The one or more proteins comprise one or more of VEGF, BMP-2, FGF-2, PDGF, GM-CSF, IL-4, GDNF, or combinations thereof recited in instant claim 7 (co-pending claims 1 and 7). In other embodiments, the one or more affibodies comprise one or more of SEQ Id NO: 1-63, 65-74, and 77-90, and optionally an additional C-terminal Cys, Lys, Tyr (co-pending claim 8). The amino acid sequences of SEQ ID NOs: 1-63, 65-74, and 77-90 correspond to those having the same identifier recited in the instant claims.
Thus, the co-pending claims meet the limitations of instant claims 7, 8, and 9.
Conclusion
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/LIA E TAYLOR/ Examiner, Art Unit 1641
/MISOOK YU/ Supervisory Patent Examiner, Art Unit 1641
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