DETAILED ACTION
Notice of Pre-AIA or AIA Status
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. The Preliminary Amendments filed on October 26, 2025 and April 2, 2024, have been received and entered.
3. Applicant’s election without traverse of Group I (with species) on October 24, 2025, is acknowledged.
Claim Disposition
4. Claims 1-76 have been cancelled. Claims 77-94 have been added and are pending. Claims 77-94 are under examination.
Information Disclosure Statement
5. The Information Disclosure Statements filed on January 29, 2024, has been received and entered. The references cited on the PTO-1449 Form have been considered by the examiner and a copy is attached to the instant Office action.
Drawing
6. The drawings filed on January 29, 2024, have been accepted by the examiner.
Specification Objection
7. The specification is objected to for the following informalities:
The specification is objected to because the organism names are not all italicized, see page 8 (see Drosophila).
Appropriate correction is required.
Claim objection
8. Claims 77-94 are objected to for the following informalities:
For clarity and precision of claim language it is suggested that claim 77 is amended to recite “….R-spondin (RSPO)”. Claim 77 is also objected to because there are acronyms that are not spelled out. The dependent claims hereto are also included.
For clarity it is suggested that claims 87-88 should be amended to read, “RSPO1 (R-spondin 1)….” and “RSPO1 (R-spondin 2)….”
Claim 90 is objected to because the acronyms like ‘AEB, DMI’ etc., are not spelled out.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph 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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
9. Claims 74-94 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AlA), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or
a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claimed invention is directed to “a cell targeted cytotoxic construct comprising products such as a ligand, linking polypeptides, for example, however, no structural limitations are recited. In addition, the claimed invention has no functional limitations. No structure function correlation is made, and the claims encompass a large variable genus (i.e. ligands, linking polypeptides, spacer, cytotoxic moiety, see claim 77 for example) that is not adequately described.
The claimed invention as directed to a cell-targeted cytotoxic construct encompasses a large variable genus of cells, sortase recognition site, spacer, auristatin, toxin or chemotherapeutic, and composition. For example, the term “auristatin” does not clearly provide the following means (i) only auristatin E, auristatin F, AEB, AEVB, AEFP, MMAE, MMAF, eleuthorobin, netropsin, podophyllotoxins, and maytansiods including maytansine and DMI, and combretestatins or (ii) any auristatin analog (for example, see Maderna et al, 2015. In addition, the structural and functional properties of auristatin E, auristatin F, AEB, AEVB, AEFP, MMAE, MMAF, eleuthorobin, netropsin, podophyllotoxins, and maytansiods including maytansine and DMI, and combretestatins are not disclosed by the specification. Therefore the invention as claimed is not adequately described. The dependent claims hereto are also included.
The claimed invention is not commensurate in scope with the disclosure and no correlation is made between structure and function. A large variable genus of products, expression products and organism are encompassed in the claims as well as modifications that are not described. The specification fails to provide a representative number of species for the claimed genus to show that applicant was in possession of the claimed genus. A representative number of species means that the species, which are adequately described, are representative of the entire genus.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, structure or other physical and/or chemical properties, by
functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), states that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed" (See page 1117). The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed" (See Vas-Cath at page 1116). The skilled artisan cannot envision the detailed chemical structure of the encompassed genus, and therefore, conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993).
Therefore, for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that the applicant had possession of the claimed invention at the time the instant application was filed.
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.
10. Claims 74-94 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.
For claims 77, 87 and 88, the terms “R-spondin”, “RSPO1” and “RSPO2” render the claim indefinite. The specification states the following.
[00117]…RSPO1 and RSPO2 have been identified as the ligands for both LGR5 and LGR6 receptors to which they bind with high affinity.
This statement provides no structural information for the terms “RSPO1” and “RSPO2” which are both types of R-spondin. The skilled artisan would not know the metes and bounds of the recited invention. It is assumed that the term “R-spondin” means any polypeptide comprising an N-terminal secretory signal peptide, 2 tandem furin-like cysteine-rich (Fu-CRD) domains, a thrombospondin type 1 repeat (TSP) domain, and a C-terminal basic amino acid-rich (BR) domain that binds to any marker for stem cells in the gut (LGR5) or any polypeptide that binds to skin and Fallopian tube epithelium (LGR6). Based on said assumption and the specification stating RSPO1 and RSPO2 are ligands for both LGR5 and LGR6 receptors, for purposes of examination the following is assumed. Taking the broadest reasonable interpretation, it is assumed that the terms “RSPO1” and “RSPO2” mean any polypeptide comprising an N-terminal secretory signal peptide, 2 tandem furin-like cysteine-rich (Fu-CRD) domains, a thrombospondin type 1 repeat (TSP) domain, and a C-terminal basic amino acid-rich (BR) domain that binds to both any marker for stem cells in the gut (LGR5) and binds to skin and Fallopian tube epithelium (LGR6).
Basis For NonStatutory Double Patenting
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. See 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);and, 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) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent is shown to be commonly owned with this application. See 37 CFR 1.130(b).
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
12. Claims 77, 79-87 and 89-92 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11,193,117. An obvious-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim is not patentably distinct from the reference claim(s) because the examined claim is either anticipated by, or would have been obvious over, the reference claim(s). See In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); and In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985). Although the conflicting claims are not identical, they are not patentably distinct from each other.
The instant application claims are directed to a cell targeted cytotoxic construct. The patented claims are directed to a cell targeted cytotoxic construct. The two sets of claims differ because the instant claims recite more structures (see for example, claim 79). Although the scope of the two sets of claims differs, the two sets of claims are an obvious variation of each other, thus prima facie obvious. This is an obvious type double patenting rejection.
13. Claims 77-94 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11,913,043. An obvious-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim is not patentably distinct from the reference claim(s) because the examined claim is either anticipated by, or would have been obvious over, the reference claim(s). See In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); and In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985). Although the conflicting claims are not identical, they are not patentably distinct from each other.
The instant application claims are directed to a cell targeted cytotoxic construct. The patented claims are directed to a cell targeted cytotoxic construct. The two sets of claims differ because the instant claims recite more structures (see for example, claim 79). Although the scope of the two sets of claims differs, the two sets of claims are an obvious variation of each other, thus prima facie obvious. This is an obvious type double patenting rejection.
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.
14. 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.
15. Claims 77-78, and 80-87 are rejected under 35 U.S.C. 103(a) as being unpatentable over Beerli et al. (PLOS ONE, 10(7), 2015, pages 1-17, of record in the application) in view of Chen et al.(Genes and Development, volume 27, pages 1345-1350, 2013, of record in the application).
Beerli teaches drug conjugates using S. aureus sortase, a sortase recognition motif LPETG, MMAE with addition of peptides, a recombinant fusion polypeptide comprising the MMAE (from Concortis; San Diego, USA) and an antibody, cell targeting polypeptide and the two spacers valine - citrulline and p- aminobenzylcarbamate (Table 1, and Abstract), wherein prior to the peptide conjugation the sortase linker was LPETG (p5/17, 2) the final fusion protein retains the LPET motif between MMAE and the antibody, and prior to peptide conjugation the spacer was Gly5 (p5/17 42). Beerli et al. teaches cancer therapies and cell directed targeting via a construct to deliver a toxic payload to cancer cells (see page 2). Beerli does not reduce to practice their recombinant MMAE -containing fusion polypeptide wherein the spacer GGGS is used for peptide conjugation. However, Beerli teaches that use of said spacer improves conjugation (p8/17 41).
In addition, Beerli does not teach use of RSPO1 as a targeting moiety. Chen teaches an RSPO1 moiety (0Q318235; supplementary information) that targets the LGR5, G — protein coupled receptor, and is a marker for stem cells. It would have been obvious to a person of ordinary skill in the art to modify the MMAE — comprising recombinant fusion polypeptide of Beerli by using the RSPO1 moiety of Chen. Motivation to do so is provided by the desire to target stem cells. The expectation of success is high, as the making of fusion proteins was well known in the art and Chen teaches an RSPO1 moiety (DQ318235; supplementary information) is a
marker for stem cells.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at the claimed invention as a whole because Beerli et al, 2015 in view of Chen et al., 2013, renders the claimed invention as obvious. It is noted that the instant rejection is supported, at least, by rationales (a)-(d), (f), and (g) derived from KSR International vs Teleflex Inc (MPEP 2141 (III). It would have been obvious to a person of ordinary skill in the art to use the GGGS spacer to promote conjugation in order to make the MMAE — containing fusion polypeptide/construct. Motivation to do so is provided by the desire to enhance protein conjugation. The expectation of success is high, as Beerli teaches that said spacer improves conjugation.
Moreover, the Supreme Court pointed out in KSR, “a patent composed of several elements is not proved obvious merely by demonstrating that each of its elements was, independently, known in the prior art.” KSR, 127 S. Ct. at 1741. The Court thus reasoned that the analysis under 35 U.S.C. 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the “inferences and creative steps that a person of ordinary skill in the art would employ.” Id. at 1741. The Court further advised that “[a] person of ordinary skill is…a person of ordinary creativity, not an automation.” Id. at 1742. Therefore, the claimed invention was obvious to make and use at the time the invention was made and was prima facie obvious.
Conclusion
16. No claims are presently allowable.
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/HOPE A ROBINSON/Primary Examiner, Art Unit 1652