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 (Claims 1-14 and 16-20; drawn to a fusion protein, a nucleic acid encoding the fusion protein, a vector comprising a nucleic acid encoding the fusion protein, a cell comprising a nucleic acid encoding the fusion protein, an a kit comprising a nucleic acid encoding the fusion protein) in the reply filed on December 16, 2025, is acknowledged.
Claim 15 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention (Group II), there being no allowable generic or linking claim.
DETAILED ACTION
The amended claims filed on May 5, 2026, have been acknowledged. Claim 2 was cancelled. Claims 1 and 16 were amended. In light of the Applicant’s elected species, claim 15 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1, 3-14, and 16-20 are pending and examined on the merits.
Priority
The applicant claims foreign priority from EP20207716.0 filed on November 16, 2021. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55, received March 30, 2023. Claims 1, 3-14, and 16-20 find support in foreign application EP20207716.0 filed on November 16, 2021.
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, 3-14, and 16-20 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 contains the trademark/trade name anticalin. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a class of small, human-derived protein binders engineered from the lipocalin scaffolds and, accordingly, the identification/description is indefinite.
Claims 3-14 and 16-20 are also rejected because of their dependency on claim 1.
Claim Rejections - 35 USC § 102
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 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.
(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.
Claims 1, 3, 5, 8-10, 16-17, and 19 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by United States Patent Application No: 20050142539 (Herman), as evidenced by Chianelli et al. (Nuclear Medicine & Biology 24: 579-586. 1997). This is a new rejection substantially similar to a previous rejection of record made in response to Applicant’s amendments to claim 1. Applicant’s traversal has been considered but is moot in response to the new rejection of record.
As an initial matter, it is noted that the nucleic acid molecule encoding the fusion protein comprising the anticalin does not require that the anticalin is bound to an exogenous ligand as the exogenous ligand would not be part of the nucleic acid itself. Therefore, all that is required is that the anticalin is capable of binding to a ligand that can be linked to a radionuclide.
Regarding claims 1, 9-10, and 16, Herman teaches a fusion protein composition comprising a multispecific ligand containing at least a first ligand binding moiety and a second ligand binding moiety, nucleic acids encoding the multispecific ligand, and host cells comprising the nucleic acid.
Herman teaches that the polynucleotide sequence encoding the multispecific ligand can comprise a signal peptide for secretion of the ligand (i.e. a secretory signal peptide);
Herman teaches that the ligand binding moiety can comprise anticalins for binding to a target ligand (i.e. specific binding to an exogenous ligand);
Herman teaches that the multispecific ligand can comprise an ABC transporter protein (which comprises multiple transmembrane domains) or a complex comprising a transmembrane protein.
Herman teaches that the second binding moiety can bind to a natural ligand, such as a cytokine (abstract and paragraphs 0013-0014, 0093, 0119, 0158, 0198-0200, 0222-0223, 0227, and 0257).
As stated above, all that is required is that the anticalin is capable of binding to a ligand that can be linked to a radionuclide. Herman teaches that cytokines can be radiolabelled (paragraphs 0171, 0223, 0227, and 0298). Herman teaches examples of radionuclides including I131 (paragraph 0385). As such, the multispecific fusion protein of Herman can bind to a radiolabelled cytokine. As such, Herman teaches all of the required limitations of claims 1, 9-10, and 16.
Regarding claims 3 and 17, Herman teaches that the nucleic acid can include a tag for purification, such as a myc tag and a His tag (paragraphs 0014 and 0487).
Regarding claim 5, Chianelli evidences that a chelator can be used to attach technetium-99m to an IL-2 cytokine (Figure 1).
Regarding claim 8, Herman teaches that the invention is directed to DNA or to a vector or other vehicle suitable for gene therapy comprising DNA and that the use of AAV vectors to deliver DNA for gene therapy is a well known option (paragraphs 0014 and 0457).
Regarding claim 19, Herman teaches nucleic acids encoding their fusion protein that do not include a fluorescent protein. Herman teaches that fluorescent dyes can be conjugated to the antibody and, thus, would not be a part of the nucleic acid encoding the multispecific ligand itself (paragraph 0394).
Claims 1, 4, 7-14, and 18-19 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by United States Patent No: 10428141 (Orentas), as evidenced by Wei et al. (Molecular Cancer 23: 1-17. 2024) and Badar et al. (EJNMMI Research 4: 1-8. 2014). This is a new rejection substantially similar to a previous rejection of record made in response to Applicant’s amendments to claim 1. Applicant’s traversal has been considered but is moot in response to the new rejection of record.
As an initial matter, it is noted that the nucleic acid molecule encoding the fusion protein comprising the anticalin does not require that the anticalin is bound to an exogenous ligand as the exogenous ligand would not be part of the nucleic acid itself. Therefore, all that is required is that the anticalin is capable of binding to a ligand that can be linked to a radionuclide.
Regarding claims 1, 7-11, and 16, Orentas teaches a nucleic acid encoding a chimeric antigen receptor (a fusion protein) comprising:
A secretory signal peptide;
at least one anticalin that binds to ROR1 (an exogenous ligand); and
a CD28 or CD4 transmembrane domain.
Orentas teaches that the CAR can be contained in a vector, such as a retrovirus.
Orentas teaches host cells, including CD8+ T cells (a lymphocyte), comprising the nucleic acid encoding a chimeric antigen receptor and host cells comprising the CAR protein (column 5, line 29-column 10, line 13, column 23, lines 18-26).
Wei evidences that ROR1 can be His-tagged (page 3, column 1, paragraph 5) and Badar evidences that His-tagged proteins can be radiolabelled with Technetium-99m (whole document).
Regarding claims 4 and 18, Orentas teaches that CARs can be modified to express a detectable marker, such as GFP (column 8, lines 55-59, column 34, line 51-column 35, line 22, column 38, line 64-column 39, line 6, column 42, lines 26-35).
Regarding claim 12, Orentas teaches host cells, including CD8+ T cells (a lymphocyte), comprising the nucleic acid encoding a chimeric antigen receptor and host cells comprising the CAR protein (column 5, line 29-column 10, line 13, column 23, lines 18-26). As part of expressing the CAR in the host cell, the host cell would have CAR proteins and the nucleic acid encoding the CAR at the same time.
Regarding claim 13, Orentas teaches kits comprising the nucleic acid encoding the CAR and conjugated, such as ligands (column 31, lines 11-27 and column 47, lines 7-55).
Regarding claim 14, Orentas teaches that the cell comprising the nucleic acid encoding the CAR can be used to treat cancer (column 41, line 57-column 42, line 51).
Regarding claim 19, Orentas teaches that the nucleic acid encoding the CAR can be labeled with an enzyme instead of using fluorescence (column 42, lines 26-35). This nucleic acid would not include a fluorescent protein.
Claim Rejections - 35 USC § 103
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 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.
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 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over United States Patent Application No: 20050142539 (Herman) as applied to claim 1 above and further in view of United States Patent Application No: 20080196113 (Fitzgerald).
The teachings of Herman are as discussed above. Herman teaches that a polynucleotide sequence encoding a signal peptide can also be included to allow a ligand polypeptide to cross or lodge in cell membranes or be secreted from the cell (paragraph 0257).
Herman is silent regarding the secretory signal sequence.
However, Fitzgerald teaches a nucleic acid encoding a fusion protein comprising a nucleic acid sequencing encoding mature exons 1 and 2 of INSP153 and comprising:
Fitzgerald teaches that the sequence can include a secretory sequence for purifying the mature polypeptide sequence and that exon 1 of INSP153 includes a signal peptide sequence;
Fitzgerald teaches that INSP153 is a lipocalin protein;
Fitzgerald teaches that the fusion protein can be modified to include a GPI anchor.
Fitzgerald teaches that the invention provides a vector, such as retroviruses and adenoviruses, that contains the nucleic acid molecule encoding the fusion protein and a host cell transformed with the vector (paragraphs 0053-0061, 0103-0104, 0108-0113, 0172, 0285, claims 54-56, and Figure 9).
It would have been obvious that the INSP153 signal peptide sequence could have been used as the sequence for the secretory signal peptide as Herman and Fitzgerald both generate nucleic acids encoding fusion proteins comprising lipocalin-based binding molecules (anticalins and INSP153, respectively) and both highlight the usefulness of secretory signals for secretion of the mature polypeptide sequence which allows for easier purification of the fusion protein. As Fitzgerald uses a naturally occurring secretory signal found in exon 1 of INSP153, it would have been well understood that this secretory signal could also be used with other fusion proteins that comprise lipocalin-based binding molecules. Furthermore, the successful cloning and sequencing of a DNA encoding a known gene and making an amino acid sequence is obvious, and thus unpatentable, if (1) there was some suggestion or motivation in the prior art to clone the DNA, and (2) there was a “reasonable expectation of success,” based on "detailed enabling methodology" in the prior art. Ex parte Kubin, 83 U.S.P.Q.2d (BNA) 1410 (B.P.A.I. 2007), aff'd, 561 F.3d 1351 (Fed. Cir. 2009). Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Claims 1, 5, 9-10, 16, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Rauth et al. (Biochem. J. 473: 1563-1578. 2016) and further in view of Müller (J Bioproces Biotechniq 2: 1-21. 2012), as evidenced by Fani et al. (Eur J Nucl Med Mol Imaging 39 (Suppl 1):S11–S30. 2012). This is a new rejection substantially similar to a previous rejection of record made in response to Applicant’s amendments to claim 1. Applicant’s traversal has been considered but is moot in response to the new rejection of record.
As an initial matter, it is noted that the nucleic acid molecule encoding the fusion protein comprising the anticalin does not require that the anticalin is bound to an exogenous ligand as the exogenous ligand would not be part of the nucleic acid itself. Therefore, all that is required is that the anticalin is capable of binding to a ligand that can be linked to a radionuclide.
Regarding claims 1, 5, 9-10, and 16, Rauth teaches engineering three anticalins based on a human lipocalin scaffold that bind to the VFFAED epitope associated with Amyloid beta (abstract and Figure 4). As can be seen in Figure 4, the anticalins bind to hexamer and decamer peptides comprising the epitope. Rauth teaches that these Anticalins provide useful protein reagents to study the molecular pathology of Alzheimer’s disease.
Fani evidences that peptides can be radiolabelled with radionuclides, such as Technetium-99m, using a bifunctional chelator (whole document).
Rauth does not teach a nucleic acid encoding their anticalin nor wherein the anticalin includes a secretory signal peptide and a GPI anchored domain.
However, Muller teaches that protein chips are useful for understanding the pathophysiology of common multifactorial diseases, such as determining protein expression, profiling cell surface markers, identifying biomarkers, and measuring diagnostic factors. Muller teaches that protein chips have the issue of non-quantitative detection and immobilization, respectively, of the (indirectly and directly tagged) analytes in course of (partial) masking of the epitopes recognized by the immobilizing anticalin. The problem may be (partially) overcome by a novel type of protein chip that is based on glycosylphosphatidylinositol- (GPI-) anchored proteins (GPI-proteins). Muller teaches that recombinant nucleic acids encoding anticalins as part of a plasmid can be modified to include a signal sequence I (a secretory signal peptide) and signal sequence II (a GPI anchor domain) to generate a GPI-anchored protein in a transfected host cell for improved protein analysis (page 10, column 1, paragraph 3-pagte 12, column 2, paragraph 2 and Figure 8).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the anticalin of Rauth by including a secretory signal and a GPI anchored domain as part of a nucleic acid encoding the anticalin, as identified by Muller, to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to modify with a reasonable expectation of success because Rauth discusses using their anticalins to study the molecular pathology of Alzheimer’s disease and Muller teaches that protein chips are useful for understanding the pathophysiology of common multifactorial diseases, such as determining protein expression, profiling cell surface markers, identifying biomarkers, and measuring diagnostic factors. Therefore, it would have been obvious to consider using the anticalin of Rauth as part of a protein chip to study the pathophysiology of amyloid beta and, by extension, Alzheimer’s disease.
Furthermore, Muller teaches that protein chips have the issue of non-quantitative detection and immobilization, respectively, of the (indirectly and directly tagged) analytes in course of (partial) masking of the epitopes recognized by the immobilizing anticalin. The problem may be (partially) overcome by a novel type of protein chip that is based on glycosylphosphatidylinositol- (GPI-) anchored proteins (GPI-proteins). Muller teaches that recombinant nucleic acids encoding anticalins as part of a plasmid can be modified to include a signal sequence I (a secretory signal peptide) and signal sequence II (a GPI anchor domain) to generate a GPI-anchored protein in a transfected host cell for improved protein analysis. Therefore, it would have been obvious to modify the anticalin of Rauth as part of the protein chip to include signal sequences I and II as this will improve detection and immobilization.
As Muller uses their GPI anchored protein chips as part of a plasmid system to express the anticalin of interest, it would have been obvious to make this a nucleic acid and transfect a host cell with the nucleic acid encoding the anticalin fusion protein to express the anticalin fusion protein on the surface of the host cell. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Regarding claim 19, as can be seen in Figure 8 of Muller, there is no fluorescent protein encoded by the nucleic acid.
Regarding claim 20, as stated supra, Rauth teaches that their anticalins that bind amyloid beta bind hexamer and decamer epitopes (Figure 4).
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KEENAN A BATES whose telephone number is (571)270-0727. The examiner can normally be reached M-F 7:30-5:00.
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/KEENAN A BATES/Examiner, Art Unit 1631
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