DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s response and amendments received March 10, 2026 are acknowledged.
Claims 1-97 have been canceled.
Claims 98-116 are pending in the instant application.
Applicant’s election without traverse of the invention of group I, drawn to fusion proteins, and the fusion protein species of VP025 which is a heterodimer comprising the polypeptide chains VP019 (SEQ ID NO:90) and VP020 (SEQ ID NO:91) in the reply filed on March 10, 2026 is acknowledged.
Claims 113-116 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on March 10, 2026.
Claims 98-112 are under examination in this office action as they read upon fusion constructs comprising the polypeptides of SEQ ID NOs:90 and 91. It should be noted that SEQ ID NOs:90 and 91 are free of the prior art and thus the species search was extended and stopped upon finding art which reads upon the generic invention.
Information Disclosure Statement
The IDS forms received 2/17/2023, 5/16/2023, 10/30/24, 9/8/2025 are acknowledged and the references cited therein have been decided.
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.
Claims 98-112 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain 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 inventors, at the time the application was filed, had possession of the claimed invention.
Applicant has broadly claimed fusion proteins defined by what they do, i.e. their functional properties, rather than what they are, i.e. their structure. Specifically, independent claim 98 recites a fusion construct that comprises 1) an Ig-Fc or other protein scaffold, 2) a polypeptide that binds phosphatidylserine (PS) and 3) a polypeptide that binds a microbial PAMP. Dependent claims add some level of specific structure, as can be seen in for example claims 99, 103 and 104, while others simply recite intended uses for the claimed fusion protein which fail to provide additional structure to that which has been claimed as can be seen in claims 109 and 110 or recite additional functional properties such as claim 105. Other claims recite additional function which may or may not be accompanied by a structure preforming said function, such as binding CD3 as recited in claim 102. To support such breadth, the specification appears to disclose fusion proteins wherein the C terminus of the extracellular domains of human TIM-1 or DC-SIGN (aka CD209) were joined to the N terminus of immunoglobulin Fc domains, with some constructs also comprising a scFv that binds CD3. Notably, both TIM-1 and DC-SIGN are known in the art to bind structures associated with microbes (i.e. they bind Pathogen Associated Molecular Patterns (PAMP)) with TIM-1 binding PS and DC-SIGN binding many C-type lectins (see most particularly pages 3-5 of the instant specification).
The guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, § 1 "Written Description" Requirement make clear that if a claimed genus does not show actual reduction to practice for a representative number of species, then the Requirement may be alternatively met by reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., 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 genus (Federal Register, Vol. 66, No. 4, pages 1099-1 111, January 5, 2001, see especially page 1106 column 3). In The Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412) 19 F. 3d 1559, the court held that disclosure of a single member of a genus (rat insulin) did not provide adequate written support for the claimed genus (all mammalian insulins). In this same case, the court also noted: “A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is. See Fiers, 984 F.2d at 1169-71,25 USPQ2d at 1605-06 (discussing Amgen). It is only a definition of a useful result rather than a definition of what achieves that result. Many such genes may achieve that result. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder. 736 F.2d 1516, 1521,222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin [e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). Accordingly, naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material.” The court has further stated that “Adequate written description requires a precise definition, such as by structure, formula, chemical name or physical properties, not a mere wish or plan for obtaining the claimed chemical invention.” Id. at 1566, 43 USPQ2d at 1404 (quoting Fiers, 984 F.2d at 1171,25 USPQ2d at 1606). Also see Enzo-Biochem v. Gen-Probe 01 -1230 (CAFC 2002). Recent court cases have emphasized the need for correlation between a well-defined structure and recited functional limitations. For example, the courts have indicated that recitation of an antibody which has specific functional properties in the absence of knowledge of the antibody sequences that give rise to said functional properties do not satisfy the requirements for written description. See for example AbbVie Deutschland GmbH v. Janssen Biotech. Inc. 759 F.3d 1285 (Fed. Cir. 2014) as well as Amgen v. Sanofi. (Fed Cir, 2017-1480. 10/5/2017). Indeed, in Amgen the court indicates that that it is improper to allow patentees to claim antibodies by describing something that is not the invention, i.e. the antigen, as knowledge of the chemical structure of an antigen does not give the required kind of structure-identifying information about the corresponding antibodies, with the antibody-antigen relationship be analogized as a search for a key on a ring with a million keys on it. As such, knowledge of where an antibody binds provides no information as to what such an antibody necessarily looks like (i.e. its primary amino acid structure). Applicant is reminded that the courts have long ruled that “Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features.” See University of Rochester. 358 F.3d at 927, 69 USPQ2d at 1895. As such, disclosure of a screening assay to test for functional properties of an antibody or other polypeptide (such as the epitope to which a test antibody or polypeptide binds or the fact that it does or does not inhibit some biological process) does not provide evidence of possession of the product itself.
As discussed above, the specification provides working examples of fusion proteins wherein the carbohydrate binding domain of TIM-1 and DC-SIGN were joined to an immunoglobulin Fc domain. Such constructs wherein a carbohydrate binding domain of a receptor is joined to an immunoglobulin Fc are well known in the art as evidenced by Hsu et al. and are often used to identify the carbohydrate residue(s) responsible for receptor binding (see entire document). However, “C-type lectins” are a broad genus of polypeptides, which differ wildly in the nature of the carbohydrates to which they bind and many do not bind carbohydrate at all but rather as specific for polypeptides, lipids, and other organic molecules (Cummings et al., see entire document, particularly the section titled Definition of C-type Lectins and Structural motifs). Thus, the art demonstrates that it is the specific structure of the polypeptide in question which determines ligand specificity. Apart from claims 99, 100, 103, and 104 which recite sequences of TIM-1 and/or DC-SIGN which are known to bind microbial PAMPs, the other claims simply recite the function of binding a PAMP and PS in the absence of any specific structure which is correlated with this function. It should be pointed out that antibodies are polypeptides, and large numbers of court decisions have made it abundantly clear that claiming a product based upon what the product binds rather than what the product is (i.e. the structure of the product) does not satisfy the requirements for written description of the claimed product. As such, claims reciting a polypeptide (antibody or otherwise) that binds an antigen, like a PAMP, lack written description as there is no correlation between structure and function recited in such claims (apart from those reciting SEQ ID NOs:1-4 as discussed above) and the specification fails to disclose a representative number of species within the genus as the two examples of the specification, namely TIM-1 and DC-SIGN, are not reasonably representative of the genus of all possible polypeptides binding a PAMP or PS. Further, a scaffold reasonably is used to hold other elements in place, but as presently recited both the purpose as well as the identity of the “other protein scaffold” as recited in independent claim 1 are unknown. Given that all of the working examples appear to utilized immunoglobulin Fc domains, there do not appear to be a representative number of such “other scaffolds” disclosed in the specification as claim 98 reasonably appears to indicate that an Ig-Fc is distinct from an “other protein scaffold”.
In addition to binding PS and PAMP, dependent claims add the further function of binding CD3. Antibodies, including single chain Fv (scFv) which bind CD3 are extremely well known in the art, and indeed the instant application provides the polypeptide sequences of many anti-CD3 scFv in table 6, many of which were used in working examples in the generation of tri-functional constructs binding PS, PAMP, and CD3. However, the instant claim do not require antigen binding portions of an anti-CD3 antibody, such as a scFv, but instead recite broader terminology including “a CD3 binding protein” and “comprises CDR regions according to SEQ ID NOs:54-59”. While it is true that the recited CDR sequences are from a known anti-CD3 antibody, the claims as presently recited do not require the CDRs to be present in an antibody structure. For example, a polypeptide comprising CDRs of SEQ ID NOs: 54-59 encompasses a linear head to tail fusion of said CDRs and is distinct from an antibody that binds CD3 and comprises CDRs of SEQ ID NOs:54-59. It should be pointed out that it is well established in the art that the formation of an intact antigen-binding site requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three different complementarity determining regions, CDR1, 2 and 3, which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin (Janeway et al., see entire selection). Thus, the CDR sequences absent their proper three dimensional orientation as dictated by the structure of the antigen binding domain of an antibody are not reasonably expected to provide for the function of antigen binding. Applicant does not appear to have disclosed any structures that bind CD3 apart from scFv, and antibodies are not reasonably representative of the structure of any and all possible “CD3 binding proteins”.
Therefore, In view of all of the above, artisans world reasonably conclude that applicant was not in possession of the full breadth of claimed fusion constructs at the time the instant application was filed.
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.
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 98-101 and 105-112 are rejected under 35 U.S.C. 103 as being unpatentable over Hoo et al. (US 2005/0276756) in view of Geijtenbeek et al. (US 2006/0104975) and in view of Lo et al. (US 2004/0053366).
Hoo et al. disclose TIM-Fc fusion proteins and their administration to treat infections and cancer (see entire document, particularly the abstract, claims, and paragraphs [0066] and [0075], most particularly claims 7, 19, 30, and 36). Notably, SEQ ID NO:1 of the instant application is human TIM-1, and Hoo et al. disclose the use of human TIM-1 in their Fc fusion constructs (see for example paragraphs [0055-0059] and example II). Infections are disclosed as being caused by bacterial, viral, fungal and parasitic organisms and include dengue virus, coronaviruses, Ebola virus, leishmania, and mycobacteria (see particularly paragraphs [0067-0071] and [0074]). Additionally, such constructs are disclosed as containing human IgG1, IgG3, IgG4, and IgM Fc (see particularly paragraphs [0062] and [0141]) and as comprising the K322A mutation to make a “null Fc” (see particularly paragraph [0063] and compare to the “null Fc” definition found on page 21 of the instant specification). Such constructs are further disclosed as being conjugated to diagnostic and therapeutic moieties including cytotoxic drugs (see particularly paragraphs [0089-0101]). The constructs of Hoo et al. are disclosed as being present in pharmaceutical compositions suitable for administration via a wide variety of routes including oral and injection (see for example paragraph [0109]). These teachings differ from the instant claimed invention in that the fusion constructs of Hoo et al. are not disclosed as additionally containing DC-SIGN
Geijtenbeek et al. disclose DC-SIGN-Fc fusion proteins (see entire document, particularly paragraphs [0011], [0014], [00106], [0117-0118], and [0227], Figure 35, and the claims). Notably, DC-SIGN-Fc is disclosed as binding to microbes including HCV, HIV, Ebola virus, H. pylori, Leishmania, and M. tuberculosis (see for example Figure 35 and paragraphs [0018], [0169], [0197-0198], and [0201]). DC-SIGN is disclosed as binding high mannose and other carbohydrate structures (see particularly Figure 1 and paragraphs [0017], [0018], [0023], [0030], and [0195]).
Lo et al. disclose that one or more heterologous polypeptides can be joined to an immunoglobulin Fc domain, that such heterologous polypeptides can be joined to the N terminus, the C terminus, or both the N and C termini of the Fc domain simultaneously, and that the heterologous polypeptides can be non-identical (see entire document, particularly paragraphs [0040-0043]). Notably, it is taught that in fusion proteins comprising more than one heterologous non-Fc polypeptide, the heterologous polypeptide domains have their own function such that in a multivalent molecule the functions of the heterologous polypeptides may be additive or synergistic (see particularly paragraph [0043]). Notably, it is disclosed that the Fc-fusion constructs of Lo et al. can consist of a single polypeptide chain or can be higher order complexes comprising more than one polypeptide chain due to the self-dimerization properties of the Fc domain, and that the polypeptide chains that form such structures can be the same or different in sequence (see particularly Figure 1 and paragraphs [0036-0045] and [0075]).
Therefore, it would have been obvious to an ordinary artisan to make a fusion construct that contained TIM-1, Fc, and DC-SIGN. The artisan would be motivated to do so because constructs comprising TIM-1-Fc and DC-SIGN-Fc were known in the art to be useful for treating microbial infections as taught by Hoo et al. and Geijtenbeek et al. respectively. Indeed, the courts have long ruled that "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Fc fusion constructs comprising more than one heterologous domain were well known in the art prior to the time of filing as evidenced by Lo et al. and thus artisans would enjoy a reasonable expectation of success in making such a construct that would be used in methods of treating infections as taught by both Hoo et al. and Geijtenbeek et al.
Double Patenting
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 98-100 and 103-112 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 11,197,910. Although the claims at issue are not identical, they are not patentably distinct from each other because the issued claims anticipate the breadth of what is presently claimed.
Specifically, the issued claims recite heterodimeric fusion constructs comprising two polypeptide chains, wherein the chains dimerize via an Fc domain, with one chain binding phosphatidyl serine via a TIM-1 domain and the other chain binding a PAMP via DC-SIGN (aka CD209), wherein the polypeptide chains are required to comprise exact polypeptide sequences recited by SEQ ID number (see all issued claims, particularly claim 1). Notably the biological sequences recited in the instant claims are identical to those recited in the instant claims (for example issued claim 1 recites SEQ ID NOs:1 and 2 which are recited in instant claim 103, and issued claim 1 also recites SEQ ID NOs: 3 and 4 which are also recited in instant claim 104, and note the bib data sheet for the instant application indicates the instant application is a CON of the application giving rise to the ‘910 patent). The issued claims recite that such constructs are to be administered to treat infections by various organisms including viruses, mycobacterium and fungi (see particularly issued claims 4-7 and compare to instant claims 109-110). Given that the issued claims are limited to sequences defined by non-degenerate SEQ ID numbers for the Fc, TIM-1, and DC-SIGN moieties (see again issued claim 1) they necessarily anticipate the breadth of what is presently claimed.
No claims are allowable.
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Michael Szperka
Primary Examiner
Art Unit 1641
/MICHAEL SZPERKA/Primary Examiner, Art Unit 1641
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