DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant's amendment and remarks filed on 07/15/2026 are acknowledged.
Claims 1, 10-12 and 14-23 are pending.
3. Applicant’s election of the invention of Group I in the reply filed on 07/15/2026 is acknowledged. Applicant further elected the species of PTPEO and IGF-1.
Because Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
All presently pending claims read on the elected invention.
4. Claim 17 is objected to as failing to comply with 37 CFR 1.831(c), because it recites a sequence containing 4 or more specifically defined amino acids which is not identified by a sequence identifier (i.e., “SEQ ID NO:X” or the like). Applicant is required to amend the claim to comply with the requirements of the sequence rules (37 CFR 1.831 - 1.835) in response to this Office Action. See MPEP 2412.
5. 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.
6. Claims 11-12 and 16-17 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
(i) Claim 11 is indefinite in the recitation of “variant” or “fragment” of the recited proteins, because neither the nature or degree of “variation” nor the minimal size or properties of a “fragment” required for it to be within the scope of the claim is defined.
(ii) Claim 12 is indefinite, because the recitation of “the peptide linker between the targeting domain and the half-life modulator” lacks proper antecedent basis in the preceding part of the claim. It is noted that subclause (b) contains duplicative recitations of “a peptide linker between the activator domain and half-life modulator.”
(iii) Claims 15 and 16 are indefinite, because the scope of HSA variants encompassed by the claims is not defined. The claims specify that HSA variant comprises one or more mutations which “comprise” a substitution at one or more of C58 and N527. The open language “comprise” encompasses any number of mutations, in addition to substitutions at the specified positions; therefore, the range of HAS variants within the scope of the claims is unclear.
(iv) Claim 17 is indefinite, because it encompasses the indefinite limitations of the claim on which it depends.
In view of the above, a person of ordinary skill in the art cannot unequivocally interpret the metes and bounds of the claims so as to understand how to avoid infringement. Applicant is reminded that any amendment must point to a basis in the specification so as not to add New Matter. See MPEP 714.02 and 2163.06.
7. The following is a quotation 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.
8. Claims 19-22 are rejected under 35 U.S.C. 112(a) as failing to comply with the enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The specification does not provide a sufficient enabling description of a method for treating kidney disease comprising administering a chimeric protein comprising IGF-1, or comprising a generically recited growth factor.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized in In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, limited working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to make and use the claimed invention.
Claim 19 is directed to a method for treating any kidney disease comprising administering a chimeric protein comprising any growth factor. Claim 20 subdivides kidney disease into several broad generic categories, each including conditions of various etiologies and pathogenetic mechanisms. Claim 1, on which claim 19 depends, recites a chimeric protein comprising any growth factor and a domain that targets the protein to any kidney tissue. Claim 1 encompasses an embodiment wherein the growth factor is IGF-1.
The specification describes a working example of chimeric proteins localizing to the kidney upon administration to laboratory animals (Example 4), and a prophetic example of safety and efficacy study of chimeric proteins of the invention (Example 5).
The state of the art recognizes that “growth factor” is a generic term applied to factors with positive effect on cell proliferation, among other functions, and includes numerous factors which vary widely in their tissue specificity, mechanisms of action and effects on different cell population. A person of skill in the art would also be aware that kidney diseases include a multitude of distinct pathologies, some of which have unrelated or mutually exclusive etiologies, molecular mechanisms, pathogeneses, prognoses, and treatment modalities. Based on this, a skilled artisan would understand that even if a specific growth factor is demonstrated to treat a specific kidney disease, most of other growth factors will not, and the same growth would not be expected to be therapeutic for many other kidney diseases.
Multiple studies addressed possible roles of IGF-1 in a variety of kidney pathologies, pointing to the complexity of context-dependent pathways and interactions with both positive and negative effects on pathogenesis. For example, Vasilkova et al. (2021) found that in diabetic patients, higher levels of IGF-1 are associated with chronic kidney disease (e.g. the Abstract and Implications at p. 1, and Conclusions at p. 5).
In a post-filing date review, Diaz Tocados et al. (2025) highlight multiple IGF-1 pathways thought to be involved in certain renal pathologies, including possible IGF-1 roles in promoting renal inflammation, tubular damage and fibrosis in a mouse model of diabetic kidney disease (p. 6), and exacerbation of ischemic renal damage through stimulation of neutrophil infiltration and inflammation (p. 4). Renal anabolic effects of IGF-1 can be detrimental in the context of polycystic kidney disease, as it promotes renal cell proliferation and kidney enlargement (p. 6), and can be particularly negative in the context of renal cell carcinoma (p. 4).
Enablement of a method of treating a disease requires that positive clinical outcomes be achieved with sufficient predictability. Based on the knowledge in the art, it is at best unpredictable whether delivery of IDF-1 to kidney tissue would have a positive effect in kidney disease, including the broad disease categories recited in claim 20. In view of the unpredictability of the art and the lack of sufficient guidance, direction or working examples in the specification, it would take undue trials and errors to develop therapeutic methods as recited in the claims.
9. 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.
10. Claims 1, 10-12, 14-16 and 18-23 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Antipov et al. (US 20170096469, IDS).
Antipov teaches chimeric proteins comprising a targeting domain such as an scFv (e.g. [0319], [0323]) having binding specificity to PTPRO (e.g. [0028], [0030], [0263], [0325]) and an IGF-1 variant (e.g. [0026], [0028]), thereby anticipating claims 1 and 10-11.
IGF-1 variant comprises substitutions at positions E3, Y24, Y31, and/or Y60 (e.g. [0279]), thereby anticipating claim 14.
The chimeric protein further comprises a half-life modulator such as HSA variant comprising substitutions at positions C58 and/or N527 (e.g. [0363]), thereby anticipating claims 15-16.
Claim 12 is included in the rejection, because it reads on an embodiment wherein the chimeric protein of claim 1 further comprises (a) a half-life modulator between the targeting domain and the activator domain, and (b) a peptide linker between the activator domain and half-life modulator which is glycine, serine or glycine and serine rich. Location of half-life modulator between the targeting domain and the activator domain is taught e.g. at [0249], and glycine/serine rich peptide linkers between the activator domain and half-life modulator are taught e.g. at [0378].
Pharmaceutical compositions comprising the chimeric protein are taught e.g. in the Abstract, and nucleic acids encoding the chimeric protein are taught e.g. at [0008], thereby anticipating claims 18 and 23.
Antipov envisions using the chimeric protein for treating kidney disease, thereby anticipating claims 19-22.
11. 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 of this title, 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.
12. Claims 1, 12, 14 and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Antipov et al. (US 20170096469) in view of Klein et al. (2014).
As addressed in section 10 above, Antipov teaches chimeric proteins within the scope of claims 1, 10-12 and 14-16, which comprise various peptide linkers between the targeting domain and the half-life modulator and/or between the activator domain and half-life modulator. In particular, Antipov exemplifies a linker of SEQ ID NO: 60 (e.g. [0378]), which is GSGGGSG, i.e. the same as recited in instant claim 17.
Antipov further teaches peptide linkers of 30 or more to 100 or more amino acids in length, which are preferably structured, e.g., alpha-helix rich (e.g. [0378]). While Antipov does not specifically exemplify linkers comprising tetratricopeptide repeat (TPR) domains, the advantages of using these structured, alpha-helix rich domains as linkers in chimeric proteins were appreciated by those skilled in the art before the effective filing date of the claimed invention.
For example, Klein (2014) notes that peptide linkers containing one TPR domain or tandem arrays of TPR domain repeats have properties useful in constructing fusion proteins or antibodies with enhanced binding properties (e.g. the Abstract, and p. 330). TPR domains are naturally present in a variety of human proteins, and as such may have reduced immunogenicity. These domains are optimal for use as structured linkers because of their rigid structure, and because the length of a set of tandem TPR domains corresponds predictably with the number of repeats, so that seven to eight TPRs form a complete superhelical turn with a pitch of ∼72 A (p. 326-327).
Klein’s teachings would have provided both the motivation and the expectation of success to those of ordinary skill in the art before the effective filing date of the claimed invention to utilize TPR domain-containing linkers as structured alpha-helix rich peptide linkers taught by Antipov.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
13. 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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
14. Claims 1, 10-12 and 18-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patents No. 10040840 (IDS), 11879002, and 11814443.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the claims of each of the above patents.
The claims of the patents recite a bispecific protein comprising (a) a targeting domain having a binding specificity to a target molecule associated with the surface of a cell of a tissue, and (b) an activator domain comprising a variant of human IGF-1 (claim 1 of each patent), wherein the tissue is kidney tissue (claim 18 of US ‘840, claim 3 of US ‘002, claim 1 of US ‘443).
While the claims of the patents do not exemplify scFv as a targeting domain having a binding specificity to a cell surface protein of kidney tissue, one would be at once envisaged by a person skilled in the art, being the most common type of a targeting domain used in bispecific chimeric proteins. The skilled artisan would understand that to target a protein to kidney tissue, the targeting domain would need to have binding specificity to a cell surface marker of kidney tissue, and so would at once envisage the targets recited in instant claim 10, in particular e.g. proteins such as Podocin or Podocalyxin which are known to be exclusively kidney-specific.
The patents further recite therapeutic methods comprising administering the bispecific proteins to a patient (claim 20 of US ‘840, claims 17-19 of US ‘002, claims 1-20 of US ‘443).
Claim 12 is included in the rejection because, as addressed in section 10 above, it reads on a chimeric protein comprising a half-life modulator and a glycine/serine rich linker. Half-life modulators are recited in claims 3 and 17 of US ‘840, claims 5-10 of US ‘002, and claims 2-5 of US ‘443, and glycine/serine rich linkers were routinely used in constructing chimeric proteins.
15. The following US Patents and/or copending US applications share a coinventor and/or an assignee with the present application, and disclose and/or claim subject matter similar to that of the present claims, but do not contain patented or currently pending claims which would anticipate or make obvious the presently claimed invention, at least because they do not recite targeting to kidney tissue:
US 10407512 (IDS)
US 10633425 (IDS)
US 10858450 (IDS)
US 10988547 (IDS)
US 11155593 (IDS)
US 11673970
US 12122819
US 12698347
US 12715937
USSN 18/417568 (US Pat Pub No. 20240245756)
USSN 18/836833 (US Pat Pub No. 20250144175)
USSN 18/887949 (US Pat Pub No. 20250145682)
USSN 19/152246 (US Pat Pub No. 20260226132)
USSN 19/321375 (US Pat Pub No. 20260041738)
16. Conclusion: no claim is allowed.
17. Any inquiry concerning this communication or earlier communications from the examiner should be directed to ILIA I OUSPENSKI whose telephone number is (571)272-2920. The examiner can normally be reached 9 AM - 5:30 PM.
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/ILIA I OUSPENSKI/ Primary Examiner, Art Unit 1644
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