DETAILED ACTION
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 in the reply filed on 9/24/2025 is acknowledged:
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Based on election, claims 42, 44-61 read on the elected invention and are treated on the merits, below. Claim 43 is withdrawn from consideration as covering a non-elected invention.
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 42, 44-61 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 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 rejected claims cover substituted polypeptides having at least 95% sequence identity to an interleukin-10 (IL10) polypeptide having the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 16; and further comprising one or more amino acid substitution at a position corresponding to an amino acid residue selected from the group consisting of X100, X25, X14, X18, X24, X28, X74, X90, X92, X96, and X104 of SEQ ID NO: 1 or SEQ ID NO: 16.
To satisfy the written-description requirement, the specification must describe every element of the claimed invention in sufficient detail so that one of ordinary skill in the art would recognize that the inventor possessed the claimed invention at the time of filing. Vas-Cath, 935 F.3d at 1563; see also Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997) (patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention”); In re Gosteli, 872 F.2d 1008, 1012 (Fed. Cir. 1989) (“the description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed”).
With regard to the recited genus of an amino acid sequence having at least 95% sequence identity to an interleukin-10 (IL10) polypeptide having the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 16; and further comprising one or more amino acid substitution at a position corresponding to an amino acid residue selected from the group consisting of X100, X25, X14, X18, X24, X28, X74, X90, X92, X96, and X104 of SEQ ID NO: 1 or SEQ ID NO: 16, the following applies:
Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 94 USPQ2d 1161 (Fed. Cir. 2010) states that “...a generic claim may define the boundaries of a vast genus of chemical compounds...the question may still remain whether the specification, including the original claim language, demonstrates that the applicant invented species sufficient to support a claim to a genus”. See page 1171.
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, 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 claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
See also Fujikawa v. Wattanasin, 93 F.3d 1559, 1571, 39 USPQ2d 1895, 1905 (Fed. Cir. 1996) (a “laundry list” disclosure of every possible moiety does not constitute a written description of every species in a genus because it would not “reasonably lead” those skilled in the art to any particular species.
Amgen, Inc. v. Chugai Pharmaceutical Co., Ltd., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) states that “it is well established in our law that conception of a chemical compound requires that the inventor be able to define it so as to distinguish it from other materials, and to describe how to obtain it”.
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or structural features common to the members of the genus, which features constitute a substantial portion of the genus, so that one of skill in the art can “visualize or recognize” the members of the genus (Emphasis added). Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997).
A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004)(“[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”). “A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when ... the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.” In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).
In Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. At section B(i), the court states, "An adequate written description of a DNA ... 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."
Courts have stated that “[i]n claims involving [non-genetic] chemical materials, generic formulae usually indicate with specificity what the generic claims encompass. One skilled in the art can distinguish such a formula from others and can identify many of the species that the claims encompass. Accordingly, such a formula is normally an adequate description of the claimed genus.” Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997), cert. denied, 523 U.S. 1089 (1998). (emphasis added).
However, there is no such specificity here, nor could one skilled in the art identify an IL-10 polypeptide encompassed by the claims. Specifically, Applicant fails to disclose any other IL-10 polypeptides, besides those covered by the specific SEQ ID NO’s in the specification and claims, and in relation to the above, these disclosed species or subgenre do not represent the substantial variety covered by the genus of an amino acid sequence having at least 95% sequence identity to an interleukin-10 (IL10) polypeptide having the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 16.
With regard to the functional definition of the IL-10 polypeptide, 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) because the specification contains almost no information by which a person of ordinary skill in the art would understand that the inventors possessed the all of the recited peptides. At best, it simply indicates that one should test an inordinate number of polypeptides to see if the proteins can perform the required function.
How much homology is required to claim a variant of a known nucleic acid sequence when the function of the nucleic acid is recited in the claims was directly answered by Ex parte Livshits (Appeal 2013-001807; US Patent Application 11/106,455):
https://www.bradley.com/insights/publications/2016/02/how-much-homology-is-enough-under--112
The answer in this case was no. The PTAB agreed with the Examiner that a PHOSITA could envision sequences that met the percent identity requirement and hybridized under the recited conditions to SEQ ID NO:3.
Further, the Examiner admitted that by using conservative substitutions, a PHOSITA could likely envision a DNA sequence that encoded a polypeptide having the same tertiary structure as the polypeptide encoded by SEQ ID NO:3.
However, the PTAB found there was no teaching that the conservation of structure (whether in the DNA or encoded polypeptide) would be a surrogate for conservation of the function claimed (over-expression of L-amino acids in the culture medium).
In other words, PTAB wanted some teaching as to which of the 5 pent of residues of the in the recited single domain antibody could be altered while still conserving the function of the encoded polypeptide.
The specification demonstrated the recited function for the polypeptide encoded by SEQ ID NO:3, but offered no teaching as to what regions of the recited protein were critical for conservation of the recited function and which regions could be modified.
The PTAB stated that the specification “leaves it to others to discover the nature and scope of substitutions, deletions, and insertions that can be made to arrive at a 95% homology sequence that additionally allows for recited activity.”
The applicants attempted to use BLAST homology data to argue that a PHOSITA would be able to address the issue, but the evidence was accorded little weight and characterized as an “invitation to experiment” by the PTAB.
The PTAB also noted that even though the DNA/polypeptides that could be envisioned by the PHOSTIA could be easily tested as set forth in the specification for conservation of the recited function, this was not enough to describe the structure so that a PHOSITA could determine “beforehand whether or not a particular structure meets the functional requirements.” As such, the PTAB held that for a nucleic acid variant which is claimed by homology and function of the expressed protein, the PHOSITA must be able to determine if the nucleic acids claimed produce a protein that accomplished the recited function from the specification itself in order to meet the written description requirement.
Therefore, in the instant case, a PHOSITA must be able to determine if the peptides claimed represent a product that accomplished the recited functions from the specification itself in order to meet the written description requirement.
However, the specification here leaves it to others to discover the nature and scope of substitutions, deletions, and insertions that can be made to arrive at a 95% homology sequence that additionally allows for the required activity since the specification offered no teaching as to what regions of the recited peptides were critical for conservation of the recited function and which regions could be modified, see In re ’318 Patent Infringement Litigation, 583 F.3d 1317, 1327 (Fed. Cir. 2009) (“[A]t the end of the day, the specification, even read in light of the knowledge of those skilled in the art, does no more than state a hypothesis and propose testing to determine the accuracy of that hypothesis. That is not sufficient.”).
The specification here also fails to teach what substitutions at residue selected from the group consisting of X100, X25, X14, X18, X24, X28, X74, X90, X92, X96, and X104 of SEQ ID NO: 1 or SEQ ID NO: 16 would preserve the recited function, besides for those substitutions specifically exemplified.
Even though the DNA/polypeptides that could be envisioned by the PHOSTIA could be easily tested as set forth in the specification for conservation of the recited function, this is not enough to describe the structure so that a PHOSITA could determine beforehand whether or not a particular structure meets the functional requirements.
The Examiner acknowledges that a working example or exemplified embodiment is not necessarily a requirement for description. However, where a generic claim term is present in a claim, as in the present application, and defined only by functional characteristics, the specification must convey enough information, e.g., via sufficient representative examples, to indicate invention of species sufficient to constitute the genus. Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 967 2 (Fed. Cir. 2002). The written description requirement “requires a description of an invention, not an indication of a result that one might achieve if one made that invention.” Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997); see also Novozymes A/S v. DuPont Nutrition Biosciences APS, 723 F.3d 1336, 1350 (Fed. Cir. 2013) (“A patent...‘is not a reward for the search, but compensation for its successful conclusion.’ ... For that reason, the written description requirement prohibits a patentee from ‘leaving it to the ... industry to complete an unfinished invention.’” (citations omitted)).
Accordingly, the specification lacks adequate written description for the recited polypeptide having at least 95% sequence identity to an interleukin-10 (IL10) polypeptide having the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 16; and further comprising one or more amino acid substitution at a position corresponding to an amino acid residue selected from the group consisting of X100, X25, X14, X18, X24, X28, X74, X90, X92, X96, and X104 of SEQ ID NO: 1 or SEQ ID NO: 16.
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.
Claim 52 is 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.
The criteria for those modifications that increase half-life in claim 52 are undefined.
Claim Rejections - 35 USC § 102
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 42, 47-54, 61 are rejected under 35 U.S.C. 102(a)(1) or 102(a)(2) as being anticipated by WO 2020082057 (WO 057), as evidenced by counterpart U.S. Publication No. 20220009986 and GenCore version 6.5.2, Copyright (c) 1993 – 2025; Biocceleration Ltd., citation BHR89338, Human mature IL-10 protein mutant N21, SEQ ID 13.
SEQ ID NO: 13 of WO 057 includes Human mature IL-10 protein mutant N21 with the required substitution and percent identity, e.g., position 21, see GenCore version 6.5.2, Copyright (c) 1993 – 2025; Biocceleration Ltd., citation BHR89338, Human mature IL-10 protein mutant N21, SEQ ID 13.
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The above sequence of IL-10, and substitution thereof, anticipates claim 42, compositions and kits thereof (see claims 53 and 61).
WO 057 teaches that one or more non-naturally encoded amino acids are incorporated in one or more of the following positions in IL-10 or a variant thereof: before position 1 (i.e. at the N-terminus), 1, 19, 32, 36, 54, 57, 58, 63, 68, 72, 75, 77, 81, 85, 88, 92, 97, 100, 101, 102, 104, 106, 108, 110, 111, 114, 117, 121, 125, 126, 127, 128, (claims 42, 47, 48), or added to the carboxyl terminus of the protein, and any combination thereof of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5. S ID NO:5.
In some embodiments, one or more non-naturally encoded amino acids are incorporated at one or more of the following positions of mature IL-10 protein or a variant thereof: position 1, 14, 18, 21, 28, 31, 36, 39, 40, 45, 50, 54, 57, 59, 63, 66, 67, 70, 74, 79, 82, 83, 84, 86, 87, 88, 90, 92, 93, 96, 99, 103, 107, 109, 110, or added to the carboxyl terminus of the protein, and any combination thereof of SEQ ID NO: 2, or SEQ ID NO: 5, see paragraph [0292] of counterpart U.S. 20220009986. See claims 42, 47, 48.
Regarding claim 54, WO 057 teaches a method for treating an acute leukemia in a mammal, comprising administering a therapeutically effective amount of an IL-10 polypeptide of the present invention to the mammal. This invention also provides a method for inhibiting proliferation of acute leukemia blast cells comprising administering a therapeutically effective dose of an IL-10 of the present invention to a mammal suffering from an acute leukemia. The invention also provides a method for treating an acute leukemia in a mammal, comprising administering a therapeutically effective amount of an IL-10 of the present invention to the mammal, wherein the IL-10 has an antiproliferative effect on acute leukemia blast cells which persists after the administration of interleukin-10 is stopped. In accordance with the methods of the present invention, the acute leukemia to be treated can be a myeloid cell leukemia such as acute myelogenous leukemia (AML) or a B cell leukemia such as acute lymphocytic leukemia (ALL). In this or any of the embodiments of the present invention, the PEG-IL-10 can comprise the full-length, mature (lacking the signal peptide), human interleukin-10 linked to a PEG polymer. In this or any of the embodiments of the present invention, the PEG-IL-10 can comprise the full-length, mature (lacking the signal peptide), human interleukin-10 linked to a PEG polymer or other biologically active molecule by a covalent bond. In some embodiments, the biologically active molecule may include one or more non-naturally encoded amino acids, see paragraph [0026] of counterpart U.S. 20220009986.
WO 057 teaches that prolonged biological half-life that is obtained by construction of the IL-10 polypeptide with or without conjugation of the polypeptide to a water soluble polymer moiety (claim 52). The rapid post administration decrease of IL-10 polypeptide serum concentrations has made it important to evaluate biological responses to treatment with conjugated and non-conjugated IL-10 polypeptide and variants thereof. The conjugated and non-conjugated IL-10 polypeptide and variants thereof of the present invention may have prolonged serum half-lives also after administration via, e.g. subcutaneous or i.v. administration, making it possible to measure by, e.g. ELISA method or by a primary screening assay. ELISA or RIA kits from commercial sources may be used such as Invitrogen (Carlsbad, Calif.). Measurement of in vivo biological half-life is carried out as described herein, see paragraph [0378] of counterpart U.S. 20220009986.
Expression systems, including kits, are taught, see paragraphs [0297+] (claims 49-51, 53-54, 61).
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.
Claims 44-46, 55-60 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2020082057 (WO 057), as evidenced by counterpart U.S. Publication No. 20220009986 and GenCore version 6.5.2, Copyright (c) 1993 – 2025; Biocceleration Ltd., citation BHR89338, Human mature IL-10 protein mutant N21, SEQ ID 13.
The rejected claims recite pharmacological effects of the recited IL-10 polypeptide which may not be explicitly taught by WO 057:
Altered binding affinity for IL-10Rβ, claims 44-46;
Confers a cell-type IL-10 biased signaling of the downstream signal transduction mediated through IL-10 compared to a reference IL-10 polypeptide lacking the one or more amino acid substitution, claim 55;
wherein the cell-type biased IL-10 signaling comprises a reduction of STAT1- or STAT3-mediated pro-inflammatory function in B cells, T cells, and NK cells while substantially retaining its STAT3-mediated anti-inflammatory function in monocytes and macrophages, claim 56.
or wherein the STAT3-mediated proinflammatory function is selected from the group consisting of cytokine production, chemokine production, immune cell proliferation, and immune cell recruitment claim 57; or wherein the STAT3-mediated proinflammatory function is reduced from about 20% to about 100%, claim 58;
Results in a reduced capacity to induce expression of a pro-inflammatory gene selected from IFN-Ɣ, granzyme B, granzyme A, perforin, TNF-α, GM-CSF, and MIP-1α in the subject, claim 59; or
Wherein the administered composition stimulates expression of interferon gamma (INFy) in CD8-+ T cells, claim 60.
However, WO 057 teaches substantially the same IL-10 polypeptides covered by the instant claims and its administration. In this way, the above pharmacological effects are necessarily an aspect of administration of the IL-10 polypeptides described by WO 057, see MPEP 2112.01 (““Products of identical chemical composition can not have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.”). Accordingly, the above effects are an invariable aspect of the administration of the IL-10 polypeptides of WO 057, and therefore, at least prima facie obvious.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARL J PUTTLITZ whose telephone number is (571)272-0645. The examiner can normally be reached on Monday to Friday from 9 a.m. to 5 p.m.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's acting supervisor, Janet Epps-Smith, can be reached at telephone number (571)272-0757. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KARL J PUTTLITZ/ Primary Examiner, Art Unit 1646