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 01/09/2026 are acknowledged.
Claims 36-54 are pending.
3. Applicant’s election of the invention of Group III in the reply filed on 01/09/2026 is acknowledged. 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.
Applicant further elected a peptide derived from the HIV Tat protein as the Species for the first ligand, immunoglobulins and fractions thereof comprising at least the Fc region as the Species for the second ligand.
Claims 43, 46 and 48-50 are withdrawn from further consideration by the Examiner under 37 C.F.R. § 1.142(b) as being drawn to nonelected Species.
Claims 36-42, 44-45, 47 and 51-54 are presently under consideration, to the extent that they read on the elected Species.
4. The disclosure is objected to because the specification at least at p. 25-30 refers to drawings, while no drawings appear to be present in the file of the application. Appropriate correction or clarification is required.
5. Claim 51 is objected to because of an apparent typographical error in the phrase “wherein in the administration is sufficient,” which contains an apparently superfluous word “in.”
Claim 53 is objected to because of an apparent typographical error in omitting the word “to” in the phrase “administering [to] the subject.”
Appropriate corrections or clarifications are required.
6. Applicant is invited to consider making the following amendments to improve the form and clarity of the claims:
Claim 37: “tumor cell proliferation in [from] the tumor.”
Claim 38: “first growth rate” and “second growth rate”.
Claim 52: use either “polyinosinic-polycytidylic acid” or “polyinosinic:polycytidylic acid” consistently at both occurrences.
7. 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.
8. Claims 36-42, 44-45, 47 and 51-54 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 36 is indefinite in the recitation of a “specific antigen of the disease to be treated,” because it is unclear how such antigens are defined. It is unknown, for example, whether the scope of the recitation is limited to antigens directly involved in the pathogenesis of the disease (and if so, how they are defined, and whether they have a positive or negative role in the pathogenesis), or include distal markers of the disease, either positive or negative.
(ii) Claim 39 is indefinite in the recitation of the phrase “such as,” because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
(iii) Claim 40 is indefinite in the recitation of a second ligand which “targets” a surface molecule, because the meaning of the term “targeting” in the context of the claims is unclear. Claim 40 depends on claim 36, which specifies that the second ligand is a “ligand of a surface molecule,” which is interpreted to mean a “ligand which binds to a surface molecule.” The use of a different term, i.e. term “targeting,” in claim 40 creates ambiguity as to whether or not the term is equivalent to “binding.”
(iv) Claim 41 is indefinite in the recitation of “the” antibodies, because it is unknown which particular antibodies the claims refer to.
(v) Claim 54 is indefinite in the recitations of “anti”-PD-1, “anti”-PDL-1 and “anti”-CTLA4, because it is unclear whether they denote antibodies, or antagonists of any structural class.
(vi) Claims 37-42, 44-45, 47 and 51-54 are further indefinite, because they encompass the indefinite limitations of the claim(s) on which they depend.
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.
9. 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.
10. Claims 36-42, 44-45, 47 and 51-54 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contain(s) 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, at the time the application was filed, had possession of the claimed invention.
The inventor or a joint inventor is not in possession of the claimed method, because the inventor or joint inventor is not in possession of a generically recited “ligand of a sulfated sugar of the glycosaminoglycan family,” or a generically recited “ligand of a surface molecule of antigen-presenting cells or of NK or NKT cells.”
Claim interpretation: the term “ligand” in the context of the present claims is interpreted as any molecule capable of binding the recited types of compounds.
The “ligands” recited in the present claims are defined solely by their function, without imposing any limitations on the structure of the molecules encompassed by each genus.
The specification discloses multiple non-limiting examples of polypeptides capable of binding to sulfated glycosaminoglycan (sGAG) ([0053]-[0053]), which differ widely in their structures. A person of skill in the art would readily understand that the genus of sGAG binding molecules is not limited to polypeptides, and may include molecules of any structural class.
The specification also discloses multiple non-limiting examples of ligands of a surface molecule of antigen-presenting cells or of NK or NKT cells ([0057]-[0067]), which also possess a very broad range of unrelated structural characteristics.
"The written description requirement.., ensures that when a patent claims a genus by its function or result, the specification recites sufficient materials to accomplish that function - a problem that is particularly acute in the biological arts." Ariad Pharms., Inc. v. Eli Lilly and Co., 598 F.3d 1336, 1352-53 (Fed. Cir. 2010) (en banc). Thus, a "sufficient description of a genus.., requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can 'visualize or recognize' the members of the genus." Id. at 1350 (quoting Regents' of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568-69 (Fed. Cir. 1997)). Accordingly, "merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species." Id. [F]unctionally defined claims can meet the written description requirement if a reasonable structure-function correlation is established, whether by the inventor as described in the specification or known in the art at the time of the filing date. Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 964 (Fed. Cir. 2002).
In the present case, although the specification discloses multiple examples of ligands within the scope of the claims, they are not representative of the extremely high diversity of structures within the respective functional genera, which possess no common structural features. Furthermore, there is no established structure-function correlation, either described in the specification or known in the art.
Adequate written description requires more than a mere statement that it is part of the invention. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993). 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 1099-1111, Friday January 5, 2001, see especially page 1106 column 3). Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear 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.). Consequently, Applicant was not in possession of the instant claimed invention. See University of California v. Eli Lilly and Co. 43 USPQ2d 1398. Applicant is directed to the Guidelines for the Examination of Patent Applications under the 35 U.S.C. 112, ¶ 1 “Written Description” Requirement, Federal Register, Vol. 66, No. 4, pages 1099-1111, January 5, 2001.
11. Claims 36-42, 44-45, 47 and 51-54 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for
a method of immunotherapy of cancer comprising the administration of a molecular complex consisting of a first ligand which is a peptide comprising amino acids 49-57 of HIV Tat protein, and a second ligand which is an Fc-containing immunoglobulin,
does not reasonably provide enablement for
(i) a method of immunotherapy of a generically recited “infectious disease,” or
(ii) a method of immunotherapy of cancer comprising the administration of a molecular complex consisting of a first ligand which is a generically recited “ligand of a sulfated sugar of the glycosaminoglycan family,” and/or a second ligand which is a generically recited “ligand of a surface molecule of antigen-presenting cells or of NK or NKT cells.”
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims without undue experimentation.
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.
(i) Regarding immunotherapy of a generically recited “infectious disease,” a person of skill in the art would be aware that the immune system comprises numerous organ systems, cell types, and signaling pathways which paly different roles in defense against distinct types of infectious agents, such as parasites, fungi, bacteria and viruses. Therefore, a skilled artisan would not expect that activation of a narrow subset of immune cells would result in positive clinical outcomes over a broad range of infectious diseases with sufficient predictability. The specification does not appear to provide sufficiently specific guidance, direction, or working examples of treating the broad range of infectious diseases, and therefore experimentation left to those skilled in the art would be unnecessarily, and improperly, extensive and undue.
(ii) Working examples disclosed in the specification describe experiments wherein fusion proteins comprising either DTRB (diphtheria toxin R domain) or a basic region of HIV Tat protein as the first domain and a ZZ derivative of protein A as the second domain, either alone or in the presence of polyclonal immunoglobulins or antibodies specific to APC/NK/NKT cells induce activation of such cells.
As pointed out at paragraph [0009] of the specification, these results are surprising because, “theoretically, it should not be capable of modulating the activity of APCs and of a large repertoire of T lymphocytes with sufficient efficacy for an immunotherapeutic effect to occur.” The molecular mechanisms of the effect discovered by the inventors is unknown, including the role, if any, of binding of the fusion proteins specifically to any sulfated sugars of the glycosaminoglycan family (sGAG). Therefore, it is unpredictable whether any of the numerous other molecules which bind to various types of sGAG would confer the same activating property to the recited molecular complex.
Likewise, there are thousands of molecules present on the surface of various types of APCs, NK, and NKT cells, including structural, inhibitory, and activatory, among others, most of which are not unique to these cell types. Further, any “ligand” binding to such molecules may have antagonistic, agonistic, or toxic effect on these cells. Therefore, it is unpredictable whether any type of ligand of any surface molecule other than those tested by the inventors would have activating effect on these cells, or lead to positive clinical outcomes.
In view of this unpredictability, a skilled artisan would reasonably conclude that the required experimentation would entail an inordinate amount of trial and error, and as such would be unnecessarily, and improperly, extensive and undue.
12. 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.
13. Claims 36-42, 44-45, 47 and 51-54 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Lee et al. (US 20150191710).
Lee teaches fusion proteins comprising a Tat peptide and an IgG Fc domain (e.g. [0016], [0017], [0146], [0147]), which is a homodimer (e.g. [0016] ) and binds heparin (e.g. [0026]). Lee’s Tat peptide comprises SEQ ID NO: 3 (e.g. [0146]), which is identical to instantly recited Tat49-57 peptide of SEQ ID NO: 3 (see SCORE). As such, Lee’s fusion proteins are structurally within the scope of molecular complexes recited at least in instant claims 36, 39, 41-42, and 44-45.
Lee teaches that the fusion proteins may further include antibodies, proteins or peptides, including therapeutic proteins such as cell growth regulators, and can be used to treat cancer or infections (e.g. [0069], [0080], [0087], [0134]). Accordingly, Lee’s teachings anticipate at least instant claims 36, 39, 41-42, and 44-45.
Claims 37, 38 and 51 are included in the rejection because, since Lee’s method is within the scope of instant claims, the outcomes of practicing Lee’s method are inherently the same as those of practicing the instantly claimed method.
Claim 40 is included, because IgG Fc domain targets receptors for the constant region of immunoglobulins on the surface of antigen-presenting cells.
Claim 47 is included, because IgG Fc domain forms homodimers, and as such is “an immunoglobulin-binding element.”
Claim 52 is included, because it recites adjuvants and carrier commonly well-known to be useful in cancer immunotherapy, and as such would be at once envisaged by those skilled in the art. Claims 53-54 are included, because they recite FDA-approved cancer immunotherapeutic agents, and as such would be at once envisaged by those skilled in the art.
14. Claims 36-38, 40-42, 44, 47 and 51-54 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Fang et al. (US 20160347817), as evidenced by Pomin VH (2016).
Fang teaches a method of treating cancer comprising administering to the subject an FGFR-Fc fusion protein (e.g. [0113]). FGFR is a ligand of sulfated glycosaminoglycans heparan sulfate and heparin, as reviewed e.g. by Pomin (2016). Accordingly, Fang’s teachings anticipate the instantly claimed method.
Claims 37-38, 40, 47 and 51-54 are included in the rejection for the same reasons as articulated in section 13 above.
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:
US Patents No. 8501193, 9816072, 10385120, and 12344661;
Copending application USSN 18547471 (US PG Pub. No. 20240182550).
16. Conclusion: no claim is allowed.
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/ILIA I OUSPENSKI/ Primary Examiner, Art Unit 1644