DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 5/8/2026 has been entered.
2. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
3. Claims 44 and 49-69 are pending. Claim 69 is new. Claims 1-43 and 45-48 are canceled. Claim 57 is withdrawn. Claims 44, 50 and 52 have been amended.
4. Claims 44, 49-56 and 58-69 are under examination.
Information Disclosure Statement
5. The information disclosure statement (IDS) submitted on 8/3/2026 has been considered by the examiner.
Rejection Withdrawn
6. The rejection of claims 52 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite because there is insufficient antecedent basis for “the IgG” is withdrawn in view of applicant’s amendments.
7. The rejection of claims 44, 49-56, 58, 59, 63, 65 and 68 remain rejected under 35 U.S.C. 103 as being unpatentable over Kimes et al. (WO 2020/172473A1, pub date: 8/27/2020, effectively filed date: 2/20/2019), in view of Saxon et al. (US 2006/0171942A1, pub. date: 8/3/2006) is withdrawn as the teachings of Saxon which the examiner relied upon was found in Kimes.
Rejection Maintained
Claim Rejections - 35 USC § 112
8. 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. Claim 60 remains 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 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.
Claim 60 is drawn to the fusion protein of claim 44, wherein said fusion protein binds specifically to a cancer antigen.
Claim 60 is rejected because the specification does not disclose any conventional antibodies that comprise less than 6 CDRs, a VH alone or a VL alone, or a single domain antibody comprising less than 3 CDRs can bind a cancer antigen.
The state of the prior art is such that it is well established in the art that the formation of an intact antigen-binding site of antibodies generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs or hypervariable regions, which provide the majority of the contact residues for the binding of the antibody to its target epitope (Paul, Fundamental Immunology, 3rd Edition, 1993, pp. 292-295, under the heading “Fv Structure and Diversity in Three Dimensions”). 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 immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites (Paul, page 293, first column, lines 3-8 and line 31 to column 2, line 9 and lines 27-30). Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al (Proc. Natl. Acad. Sci. USA, 79(6):1979-1983, March 1982). Rudikoff et al. teach that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function. Colman (Research in Immunology, 145:33-36, 1994) teaches that even a very conservative substitution may abolish binding or may have very little effect on the binding affinity (see pg. 35, top of left column and pg. 33, right column). Murphy et al. (Journal of Immunological Methods, Vol. 463, Pg. 127-133, 2018), teach that altering amino acid D92 in the complementarity determining region light chain region 3 (CDRL3) of single chain fragment variable (scFv) 2G1 obliterates its capacity to bind to microcystin-leucine-arginine (MC-LR)(Page 130, Section 3.2, paragraph 2) and changing phenylalanine at position 91 to tyrosine caused an increased in binding to MC-LR, compared to the parent clone (Page 131, Column 1, Paragraph 2). The alterations in binding that were observed in these two variants demonstrate the highly influential role of CDRL3 in binding MC-LR. Thus, the state of the art recognized that it would be highly unpredictable that a specific humanized antibody comprising less than all six CDRs of a parental antibody with a desired specificity would retain the antigen-binding function of the parental antibody. Thus, the minimal structure which the skilled artisan would consider predictive of the function of binding the antigen of the parental donor antibody includes six CDRs (i.e. VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3) from parental donor antibody in the context of framework sequences which maintain their correct spatial orientation and have the requisite binding function of the parental donor antibody. One of ordinary skill in the art could not predictably extrapolate the teachings in the specification, limited to antibodies that comprise all six CDRs of a parental donor antibody that binds antigen to antibodies that comprise fewer than all six CDRs from the parental donor antibody, wherein the antibodies retain the antigen specificity of the parental donor antibody. In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) (contrasting mechanical and electrical elements with chemical reactions and physiological activity). See also In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); In re Vaeck, 947 F.2d 488, 496, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991). One of skill in the art would neither expect nor predict the appropriate functioning of the antibodies as broadly as is claimed.
The specification does not disclose a representative number of species for the genus of antibodies comprising a CDR, a VH alone or a VL alone and binding a cancer antigen, nor does it disclose sufficient correlations between a structure and the functions (binding to a cancer antigen).
“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.” Regents of the University of California v. Eli Lilly and Co. 43 USPQ2d 1398 (Fed. Cir. 1997). The disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter of the claim. Id. 43 USPQ2d at 1406.
Therefore, only antibodies comprising all 6 CDRs or both a VH and a VL of a reference antibody, but not the full breadth of the claims meets the written description provision of 35 U.S.C. § 112 first paragraph.
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Note: The rejection of other claims based on “less than 6 CDRs” is withdrawn in view of applicant’s persuasive arguments that the claims (except claim 60) do not require the fusion protein to bind an antigen.
The rejection based on “at least 90%, 95% or 99% sequence identify with a constant domain sequence” is withdrawn in view of applicant’s persuasive arguments that the specification discloses a structure-function correlation (2.4.3 of remarks) and in view of the state of art.
Claim Rejections - 35 USC § 102
10. 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)(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.
11. Claims 44, 49-56, 58-59, 63, 65 and 68-69 remain/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Kimes et al. (WO 2020/172473A1, pub date: 8/27/2020, effectively filed date: 2/20/2019).
Regarding claim 44, Kimes et al. teaches a chimeric binding agent comprising (i) one or more of C[Symbol font/0x65]1, C[Symbol font/0x65]2, C[Symbol font/0x65]3, and/or C[Symbol font/0x65]4 domains, and (ii) one or more C[Symbol font/0x67]1, C[Symbol font/0x67]2, C[Symbol font/0x67]3 and/or a hinge region ([0006]), wherein the chimeric binding agent comprises C[Symbol font/0x65]2-C[Symbol font/0x65]3-C[Symbol font/0x65]4-C[Symbol font/0x67]2-C[Symbol font/0x67]3, or C[Symbol font/0x67]2-C[Symbol font/0x67]3- C[Symbol font/0x65]2-C[Symbol font/0x65]3-C[Symbol font/0x65]4 (see [0071]), wherein the chimeric binding agent is capable of binding to Fc[Symbol font/0x67]Rs and Fc[Symbol font/0x65]Rs, wherein Fc[Symbol font/0x67]Rs include Fc[Symbol font/0x67]RI, Fc[Symbol font/0x67]RIIA, Fc[Symbol font/0x67]RIIIA and Fc[Symbol font/0x67]RIIIB (activating Fc[Symbol font/0x67] receptor), and Fc[Symbol font/0x65]Rs include Fc[Symbol font/0x65]RI and Fc[Symbol font/0x65]RII ([0072]). Kimes et al. teaches that the chimeric binding agent may further comprise a Fab ([0067]) (which comprises 6 CDRs, a VH and a VL). Kimes et al. teaches that the chimeric binding agents may be fused to a molecule (e.g. a small molecule, a peptide, a polypeptide, or a protein) with targeting or homing function for a cell of interest or a target cell (e.g. an immune cell) ([0090]).
Regarding claim 49, Kimes et al. teaches a chimeric binding agent comprising C[Symbol font/0x65]2-C[Symbol font/0x65]3-C[Symbol font/0x65]4-C[Symbol font/0x67]2-C[Symbol font/0x67]3 or C[Symbol font/0x67]2-C[Symbol font/0x67]3-C[Symbol font/0x65]2-C[Symbol font/0x65]3-C[Symbol font/0x65]4 with a linker connecting the IgG-Fc and IgE-Fc regions, wherein the linker comprises or consists of an IgG-Fc hinge region ([0071]).
Regarding claim 50, Kimes et al. teaches that the chimeric binding agent is a tetramer ([0110]) and the chimeric binding agent is capable of binding to Fc[Symbol font/0x67]Rs and Fc[Symbol font/0x65]Rs, wherein Fc[Symbol font/0x67]Rs include Fc[Symbol font/0x67]RI, Fc[Symbol font/0x67]RIIA, Fc[Symbol font/0x67]RIIIA and Fc[Symbol font/0x67]RIIIB (activating Fc[Symbol font/0x67] receptor), and Fc[Symbol font/0x65]Rs include Fc[Symbol font/0x65]RI and Fc[Symbol font/0x65]RII ([0072]).
Regarding claim 51, Kimes et al. teaches C[Symbol font/0x65]2-C[Symbol font/0x65]3-C[Symbol font/0x65]4-C[Symbol font/0x67]2-C[Symbol font/0x67]3 (i.e. the C-terminus of the IgE-Fc region is linked to a N-terminus of an IgG Fc region) ([0071]).
Regarding claim 52, Kimes et al. teaches that the one or more C[Symbol font/0x67]1, C[Symbol font/0x67]2, C[Symbol font/0x67]3 and/or a hinge region are from IgG1([0006]).
Regarding claim 53, Kimes et al. teaches that the chimeric binding agent is capable of binding to Fc[Symbol font/0x67]Rs and Fc[Symbol font/0x65]Rs, wherein Fc[Symbol font/0x67]Rs include Fc[Symbol font/0x67]RI, Fc[Symbol font/0x67]RIIA, Fc[Symbol font/0x67]RIIIA and Fc[Symbol font/0x67]RIIIB (activating Fc[Symbol font/0x67] receptor), and Fc[Symbol font/0x65]Rs include Fc[Symbol font/0x65]RI and Fc[Symbol font/0x65]RII ([0072]).
Regarding claim 54, Kimes et al. teaches that the chimeric binding agent is capable of binding to Fc[Symbol font/0x67]Rs and Fc[Symbol font/0x65]Rs, wherein Fc[Symbol font/0x67]Rs include Fc[Symbol font/0x67]RI, Fc[Symbol font/0x67]RIIA, Fc[Symbol font/0x67]RIIIA and Fc[Symbol font/0x67]RIIIB (activating Fc[Symbol font/0x67] receptor), and Fc[Symbol font/0x65]Rs include Fc[Symbol font/0x65]RI and Fc[Symbol font/0x65]RII ([0072]).
Regarding claim 55, Kimes et al. teaches that the one or more of C[Symbol font/0x65]1, C[Symbol font/0x65]2, C[Symbol font/0x65]3, and/or C[Symbol font/0x65]4 domains are from a human or a rodent ([0102]), which inherently comprise the instant SEQ ID NOs: 2-5. Note that SEQ ID NOs: 2-5 are wild type amino acid sequences of C[Symbol font/0x65]1, C[Symbol font/0x65]2, C[Symbol font/0x65]3, and C[Symbol font/0x65]4, respectively (see applicant’s specification page 33).
Regarding claim 56, Kimes et al. teaches that the one or more C[Symbol font/0x67]1, C[Symbol font/0x67]2, C[Symbol font/0x67]3 and/or a hinge region are from human or a rodent [0102), which inherently comprise instant SEQ ID NOs: 9-11. Note SEQ ID NOs: 9-11 are wild type amino acid sequences of IgG hinge, C[Symbol font/0x67]2, C[Symbol font/0x67]3, respectively (see applicant’s specification pages 33-34).
Regarding claim 58, Kimes et al. teaches that the one or more of C[Symbol font/0x65]1, C[Symbol font/0x65]2, C[Symbol font/0x65]3, and/or C[Symbol font/0x65]4 domains are from a human or a rodent ([0102]), which inherently comprise the instant SEQ ID NOs: 2-5. Note that SEQ ID NOs: 2-5 are wild type amino acid sequences of C[Symbol font/0x65]1, C[Symbol font/0x65]2, C[Symbol font/0x65]3, and C[Symbol font/0x65]4, respectively (see applicant’s specification page 33). Kimes et al. teaches that the one or more C[Symbol font/0x67]1, C[Symbol font/0x67]2, C[Symbol font/0x67]3 and/or a hinge region are from human or a rodent [0102), which inherently comprise instant SEQ ID NOs: 9-11. Note SEQ ID NOs: 9-11 are wild type amino acid sequences of IgG hinge, C[Symbol font/0x67]2, C[Symbol font/0x67]3, respectively (see applicant’s specification pages 33-34).
Regarding claim 59, Kimes et al. teaches C[Symbol font/0x65]2-C[Symbol font/0x65]3-C[Symbol font/0x65]4-C[Symbol font/0x67]2-C[Symbol font/0x67]3 (i.e. the C-terminus of the IgE-Fc region is linked to a N-terminus of an IgG Fc region) ([0071]).
Regarding claim 63, Kimes et al. teaches that the chimeric binding agent is capable of binding to Fc[Symbol font/0x67]Rs and Fc[Symbol font/0x65]Rs, wherein Fc[Symbol font/0x67]Rs include Fc[Symbol font/0x67]RI, Fc[Symbol font/0x67]RIIA, Fc[Symbol font/0x67]RIIIA and Fc[Symbol font/0x67]RIIIB (activating Fc[Symbol font/0x67] receptor), and Fc[Symbol font/0x65]Rs include Fc[Symbol font/0x65]RI and Fc[Symbol font/0x65]RII ([0072]).
Regarding claim 65, Kimes et al. teach that the fusion protein has increased stability ([0115]).
Regarding claim 68, Kimes et al. teaches a pharmaceutical composition comprising the chimeric binding agent, and carrier ([0145]).
Regarding claim 69, Kimes et al. teaches that the chimeric binding agent is capable of binding to Fc[Symbol font/0x67]Rs and Fc[Symbol font/0x65]Rs, wherein Fc[Symbol font/0x67]Rs include Fc[Symbol font/0x67]RI, Fc[Symbol font/0x67]RIIA, Fc[Symbol font/0x67]RIIIA and Fc[Symbol font/0x67]RIIIB (activating Fc[Symbol font/0x67] receptor), and Fc[Symbol font/0x65]Rs include Fc[Symbol font/0x65]RI and Fc[Symbol font/0x65]RII ([0072]).
Applicant’s Arguments
The response states that Kimes does not disclose binding to an activating Fc[Symbol font/0x67] receptor. Kimes is directed to the prevention and treatment of allergic and inflammatory diseases. Kimes at [0062]. Specifically, Kimes provides chimeric binding agents that suppress and inactivate Fc[Symbol font/0x65]RI+ effector cells (mast cells, basophils, and eosinophils) by co-ligating Fc[Symbol font/0x65]RI with the inhibitory Fc[Symbol font/0x67]RIIB receptor. Kimes at [0063] (chimeric binding agents are provided "for suppression and/or inactivation of Fc[Symbol font/0x65]RI+ cells to induce durable and measurable anti-allergic effects"); [0063] (the chimeric binding agents "co-ligate with inhibitory (anti-inflammatory) Fc[Symbol font/0x67]Rs such as Fc[Symbol font/0x67]RIIB," and "[s]uch co-ligation of Fc[Symbol font/0x65]RI and Fc[Symbol font/0x67]RIIB can induce immunoreceptor tyrosine-based inhibition motif (ITIM) signaling that suppresses and/or inactivates Fc[Symbol font/0x65]RI+ effector cells"); [0074]
The claimed fusion protein, in contrast, requires engagement of an activating Fc[Symbol font/0x67] receptor (such as Fc[Symbol font/0x67]RI, Fc[Symbol font/0x67]RIIa, Fc[Symbol font/0x67]RIIIa, or Fc[Symbol font/0x67]RIIIb), as required by amended claim 44 and as further specified in new claim 69.
The Office Communication cites Kimes at [0072] for the proposition that the Kimes chimeric binding agent "is capable of binding to Fc[Symbol font/0x67]RI, Fc[Symbol font/0x67]RIIa, Fc[Symbol font/0x67]RIIIa, or Fc[Symbol font/0x67]RIIIb." Kimes [0072] is, however, a generic enumeration of receptors that a Kimes chimeric binding agent may potentially bind. Kimes does not disclose any specific embodiment in which the chimeric binding agent binds an activating Fc[Symbol font/0x67] receptor (i.e., a member of the enumerated list other than the inhibitory Fc[Symbol font/0x67]RIIB) simultaneously with an Fc[Symbol font/0x65] receptor. To the contrary, the only embodiments of simultaneous binding that Kimes discloses are those in which the chimeric binding agent binds Fc[Symbol font/0x65]RI and the inhibitory Fc[Symbol font/0x67]RIIB. Kimes at [0073]- [0074]. Selecting one member from the Kimes [0072] enumeration that is not disclosed in any specific Kimes embodiment, and combining it with the simultaneous-binding teaching of [0073]-[0074] that is directed to a different (inhibitory) Fc[Symbol font/0x67]R, is precisely the kind of picking, choosing, and combining that anticipation does not permit. In re Arkley, 455 F.2d at 587-89.
Kimes does not disclose the variable-domain / CDR feature of claim 44(ii). Kimes expressly identifies the absence of CDRs and Fab regions as a design rationale of the Kimes chimeric binding agents: "the binding agents herein show no or only very low immunogenicity due to a lack of complementary-determining regions (CDRs) and F(ab)2 regions." Kimes at [0063]. The Office Communication relies on Kimes at [0067] for the proposition that "the chimeric binding agent may further comprise a Fab." Office Communication at p. 18. Kimes [0067], however, is a generic catalog of possible functional domains a chimeric binding agent could potentially comprise. Read in context with the express design rationale at Kimes [0063], Kimes [0067] is not a specific disclosure of a Kimes embodiment that includes a Fab; the enabling embodiments throughout Kimes consistently lack CDRs and Fab regions, consistent with the [0063] design rationale. To the extent the Office Communication treats Kimes [0067] as a generic mention of a Fab and Kimes [0072] as a generic enumeration of FcyRs as together establishing anticipation of amended claim 44, that approach impermissibly combines parts of separate protocols within a single reference, contrary to settled anticipation law. Net MoneyIN, 545 F.3d at 1371.
Because Kimes does not disclose every element of amended claim 44 as arranged in the claim and, in particular, because Kimes does not disclose binding to an activating Fc[Symbol font/0x67] receptor or the variable-domain / CDR feature of claim 44(ii), Kimes does not anticipate amended claim 44. The claims depending there from are likewise not anticipated.
Response to Arguments
Applicant’s arguments have been carefully considered but are not persuasive. Kimes teaches a chimeric binding agent comprising C[Symbol font/0x65]2-C[Symbol font/0x65]3-C[Symbol font/0x65]4-C[Symbol font/0x67]2-C[Symbol font/0x67]3, or C[Symbol font/0x67]2-C[Symbol font/0x67]3- C[Symbol font/0x65]2-C[Symbol font/0x65]3-C[Symbol font/0x65]4 domains (see [0071], reproduced below), wherein the chimeric binding agent is capable of binding to Fc[Symbol font/0x67]Rs and Fc[Symbol font/0x65]Rs, wherein Fc[Symbol font/0x67]Rs include Fc[Symbol font/0x67]RI, Fc[Symbol font/0x67]RIIA, Fc[Symbol font/0x67]RIIIA and Fc[Symbol font/0x67]RIIIB (activating Fc[Symbol font/0x67] receptor), and Fc[Symbol font/0x65]Rs include Fc[Symbol font/0x65]RI and Fc[Symbol font/0x65]RII ([0072], reproduced below), wherein the chimeric binding agent may further comprise a Fab ([0067], reproduced below).
PNG
media_image1.png
824
703
media_image1.png
Greyscale
PNG
media_image2.png
606
785
media_image2.png
Greyscale
MPEP 2153 states
The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain.” In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)).
A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989).
Nonpreferred and alternative embodiments constitute prior art.
New Grounds of Rejection
Claim Objections
12. Claim 52 is objected to for reciting “derived from”. The term “derived from'' is not one, which has a universally accepted meaning in the art nor is it one which has been adequately described in the specification. It is unclear how the C[Symbol font/0x67]2 and/or C[Symbol font/0x67]3 domain is modified from the corresponding domains of the IgG1.
Claim Rejections - 35 USC § 112
13. 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.
14. Claims 44, 49-56 and 58-69 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for a recombinant polyclonal antibody composition comprising at least 100 first antibodies or antigen binding fragments thereof, wherein each of said antibodies or antigen binding fragments thereof binds specifically to SARS-CoV-2 and comprises all six CDRs (i.e. VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3) of a parental antibody, does not reasonably provide enablement for a recombinant polyclonal protein composition comprising at least 100 first antigen binding domains (ABPs), wherein each of the first ABPs binds specifically to SARS-CoV-2 and comprises less than 6 CDRs (i.e. VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3) of a parental antibody. 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/or use the invention commensurate in scope with these claims.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (CAFC 1988).
Wands states on page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.''
The nature of the invention and the relative level of skill
Independent claim 44 is drawn a fusion protein that binds an Fc[Symbol font/0x65] receptor and an activating Fc[Symbol font/0x67] receptor, said fusion protein comprising:(i) C[Symbol font/0x65]2, C[Symbol font/0x65]3, C[Symbol font/0x65]4, C[Symbol font/0x67]2 and C[Symbol font/0x67]3 domain, and (ii) one or more variable domains and/or one or more complementarity- determining regions (CDR), wherein the C[Symbol font/0x65]2, C[Symbol font/0x65]3, and C[Symbol font/0x65] domains provide a binding site that binds the Fc[Symbol font/0x65] receptor, and the C[Symbol font/0x67]2 and C[Symbol font/0x67]3 domains provide a binding site that binds the activating Fc[Symbol font/0x67] receptor such that the fusion protein is capable of simultaneously binding the Fc[Symbol font/0x65] receptor and the activating Fc[Symbol font/0x67] receptor.
The nature of the invention is engineered antibodies where the relative level of skill of those in the art is deemed to be high.
The breadth of the claims
The breadth of the claims encompasses a genus of fusion proteins comprising less than 6 CDRs of a parental antibody and having no antigen binding functions.
Claim 61 recites the phrase “comprising all six of the sequences from one of the following groups”. The phrase allows the fusion protein to comprise all 6 CDR sequences in any order, even consecutively without framework regions.
The working examples and guidance in the specification
The specification does not teach making fusion proteins that comprise less than 6 CDRs of a parental antibody.
The specification does not teach how to use fusion proteins comprising less than less than 6 CDRs of a parental antibody. Although the claims require the fusion protein to bind the Fc receptor, the fact that the claims require the fusion protein to comprise an antibody fragment indicates that the fusion protein is intended to bind an antigen, as evidenced by claim 60.
The scope of the claims must bear a reasonable correlation with the scope of enablement. See In re Fisher, 166 USPQ 19 24 (CCPA 1970). While it is understood that the absence of working examples should never be the sole reason for rejecting a claim as being broader than an enabling disclosure, the criticality of working examples in an unpredictable art such as antibody engineering is required for practice of the claimed invention.
The state of the prior art and unpredictability of the art
The state of the prior art is such that it is well established in the art that the formation of an intact antigen-binding site of antibodies generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs or hypervariable regions, which provide the majority of the contact residues for the binding of the antibody to its target epitope (Paul, Fundamental Immunology, 3rd Edition, 1993, pp. 292-295, under the heading “Fv Structure and Diversity in Three Dimensions”). 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 immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites (Paul, page 293, first column, lines 3-8 and line 31 to column 2, line 9 and lines 27-30). Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al (Proc. Natl. Acad. Sci. USA, 79(6):1979-1983, March 1982). Rudikoff et al. teach that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function. Colman (Research in Immunology, 145:33-36, 1994) teaches that even a very conservative substitution may abolish binding or may have very little effect on the binding affinity (see pg. 35, top of left column and pg. 33, right column). Murphy et al. (Journal of Immunological Methods, Vol. 463, Pg. 127-133, 2018), teach that altering amino acid D92 in the complementarity determining region light chain region 3 (CDRL3) of single chain fragment variable (scFv) 2G1 obliterates its capacity to bind to microcystin-leucine-arginine (MC-LR)(Page 130, Section 3.2, paragraph 2) and changing phenylalanine at position 91 to tyrosine caused an increased in binding to MC-LR, compared to the parent clone (Page 131, Column 1, Paragraph 2). The alterations in binding that were observed in these two variants demonstrate the highly influential role of CDRL3 in binding MC-LR. Thus, the state of the art recognized that it would be highly unpredictable that a specific humanized antibody comprising less than all six CDRs of a parental antibody with a desired specificity would retain the antigen-binding function of the parental antibody. Thus, the minimal structure which the skilled artisan would consider predictive of the function of binding the antigen of the parental donor antibody includes six CDRs (i.e. VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3) from parental donor antibody in the context of framework sequences which maintain their correct spatial orientation and have the requisite binding function of the parental donor antibody. One of ordinary skill in the art could not predictably extrapolate the teachings in the specification, limited to antibodies that comprise all six CDRs of a parental donor antibody that binds antigen to antibodies that comprise fewer than all six CDRs from the parental donor antibody, wherein the antibodies retain the antigen specificity of the parental donor antibody. In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) (contrasting mechanical and electrical elements with chemical reactions and physiological activity). See also In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); In re Vaeck, 947 F.2d 488, 496, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991). One of skill in the art would neither expect nor predict the appropriate functioning of the antibodies as broadly as is claimed.
In view of the lack of the predictability of the art to which the invention pertains, the lack of guidance and direction provided by applicant, and the absence of working examples for making functional fusion proteins comprising less than 6 CDRs of parental antibodies, undue experimentation would be required to make/use the claimed invention.
Claim Rejections - 35 USC § 103
15. 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.
16. Claims 44, 49-56, 58-59, 63-65 and 68-69 are rejected under 35 U.S.C. 103 as being unpatentable over Kimes et al. (WO 2020/172473A1, pub date: 8/27/2020, effectively filed date: 2/20/2019), in view of Timmer et al (US 2017/0015753A1, pub. date: 1/19/2017), and Cemerski et al. (Immunology Letters, 2012, 143: 34-43).
The teachings of Kimes et al. have been set forth above as they apply to claims 44, 49-56, 58-59, 63, 65 and 68-69.
Regarding claim 64, Kimes et al. does not teach that the hinge region in C[Symbol font/0x65]2-C[Symbol font/0x65]3-C[Symbol font/0x65]4-linker(hinge)-C[Symbol font/0x67]2-C[Symbol font/0x67]3, or C[Symbol font/0x67]2-C[Symbol font/0x67]3-linker(hinge)-C[Symbol font/0x65]2-C[Symbol font/0x65]3-C[Symbol font/0x65]4 ([0071]) is a modified IgG hinge region lacking a free cysteine residue.
Timmer et al. teaches making fusion proteins comprising a modified IgG1 hinge having the sequence of EPKSSDKTHTCPPC (SEQ ID NO: 6), where in the Cys220 that forms a disulfide with the C-terminal cysteine of the light chain is mutated to serine, e.g. Cys220Ser (C220S) ([0048]).
Cemerski et al. teaches a fusion protein comprising C[Symbol font/0x65]2-C[Symbol font/0x65]3-C[Symbol font/0x65]4-hinge-C[Symbol font/0x67]2-C[Symbol font/0x67]3, wherein C[Symbol font/0x67]2-C[Symbol font/0x67]3 is from native human IgG1, and wherein the hinge comprises a C220S substitution compared to the hinge of native human IgG1 hinge (page 35, column 2, para 2 and Fig. 2A). The hinge-C[Symbol font/0x67]2-C[Symbol font/0x67]3 of native human IgG1 inherently binds to an activating Fc[Symbol font/0x67] receptor, including Fc[Symbol font/0x67]RI, Fc[Symbol font/0x67]RIIA, Fc[Symbol font/0x67]RIIIA and Fc[Symbol font/0x67]RIIIB.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used the modified IgG1 hinge of Timmer et al. in the fusion protein comprising C[Symbol font/0x65]2-C[Symbol font/0x65]3-C[Symbol font/0x65]4-linker(hinge)-C[Symbol font/0x67]2-C[Symbol font/0x67]3, or C[Symbol font/0x67]2-C[Symbol font/0x67]3-linker(hinge)-C[Symbol font/0x65]2-C[Symbol font/0x65]3-C[Symbol font/0x65]4. One of ordinary skill in the art would have been motivated to do so because Timmer et al. teaches that Cys220 in IgG1 hinge forms a disulfide with the C-terminal cysteine of the light chain and suggested to mutate Cys220 serine ([0048]) and doing so can prevent formation of unwanted disulfide bond. One of ordinary skill in the art would have had a reasonable expectation of success because Timmer et al. teaches making fusion proteins using the modified IgG1 hinge comprising Cys220Ser mutation ([0048]), and Cemerski et al. teaches a fusion protein comprising C[Symbol font/0x65]2-C[Symbol font/0x65]3-C[Symbol font/0x65]4-hinge-C[Symbol font/0x67]2-C[Symbol font/0x67]3, wherein the hinge comprises a C220S substitution compared to the hinge of native human IgG1 hinge (page 35, column 2, para 2 and Fig. 2A).
17. Claims 44, 49-56, 58-59, 60-63, 65 and 68-69 remain rejected under 35 U.S.C. 103 as being unpatentable over Kimes et al. (WO 2020/172473A1, pub date: 8/27/2020, effectively filed date: 2/20/2019), in view of Karagiannis et al. (Cancer Immunol Immunother, 2012, 61, 1547-1564, IDS filed on 7/28/2023).
The teachings of Kimes et al. have been set forth above as they apply to claims 44, 49-56, 58-59, 63, 65 and 68-69.
Regarding claim 60, Kimes et al. does not teach that the chimeric binding agent binds a cancer antigen.
Regarding claim 61, Kimes et al. does not teach that the chimeric binding agent comprises instant SEQ ID NOs: 100-105 (which are 6 CDR sequences of trastuzumab), (see instant specification page 24, Table 1).
Regarding claim 62, Kimes et al. does not teach that the chimeric binding agent comprises SEQ ID NOs: 1 and 160 (which are VH and VL sequences of trastuzumab) (see instant specification pages 32 and 33).
Karagiannis et al. teaches that recombinant IgE antibodies including trastuzumab IgE can be used for passive immunotherapy of solid tumors (abstract). Karagiannis et al. teaches that the unique properties of IgE, a class of tissue-resident antibodies commonly associated with allergies, which can trigger powerful immune responses through strong affinity for their particular receptors on effector cells, could be employed for passive immunotherapy of solid tumors such as ovarian and breast carcinomas (abstract). Karagiannis et al. teaches that with a serum half-life of 21–24 days, compared to a half-life of 2–3 days in tissues, IgG antibodies may be the most effective antibody class to target blood-resident tumors and circulating tumor cells, while their ability to exert tumor surveillance in tissues may be less potent (p1548, last para). Karagiannis et al. teaches that the presence of IgE in the blood is short lived (half-life of 1.5 days), yet the half-life of IgE in tissues (2 weeks) is proportionately longer than that of IgG (2–3 days) (p1550, column 1). The local retention by powerful IgE receptor-expressing resident cells such as mast cells, macrophages and dendritic cells and longer immune surveillance could be beneficial in the context of cancer (p1550, column 1). Karagiannis et al. compared trastuzumab IgE with trastuzumab IgG1 and found that trastuzumab IgE directed monocytic cells to kill tumor cells expressing the HER2/neu antigen by ADCC, a mechanism clearly different from ADCP employed by trastuzumab IgG and monocytic cells (p1555, column 2). The trastuzumab IgE comprises instant SEQ ID NOs 100-105, 1 and 160.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the chimeric binding agent of Kimes to comprise a Fab region of trastuzumab in view of Karagiannis. One of ordinary skill in the art would have been motivated to do so because Kimes et al. teaches that the chimeric binding agent may further comprise a Fab ([0067]), and Karagiannis et al. teaches that trastuzumab IgE directed monocytic cells to kill tumor cells expressing the HER2/neu antigen by ADCC, a mechanism clearly different from ADCP employed by trastuzumab IgG and monocytic cells (p1555, column 2), and the unique properties of IgE, a class of tissue-resident antibodies which can trigger powerful immune responses through strong affinity for their particular receptors on effector cells, could be employed for passive immunotherapy of solid tumors such as ovarian and breast carcinomas. One of ordinary skill in the art would have had a reasonable expectation of success because Kimes teaches a chimeric binding agent comprising a Fab, IgE Fc and IgG Fc, Karagiannis et al teaches making trastuzumab IgE and has shown that trastuzumab IgE directed monocytic cells to kill tumor cells expressing the HER2/neu antigen by ADCC, a mechanism clearly different from ADCP employed by trastuzumab IgG and monocytic cells (p1555, column 2).
"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) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960).
In the instant case, both trastuzumab IgE and trastuzumab IgG were used in the prior art for killing cancer cells. It would have been obvious to combine the Fc region of IgE and the Fc region of IgG as suggested by Kimes and because such combination would allow the antibody to kill tumor cells by different mechanisms.
The fusion protein of trastuzumab IgE fused to hinge-C[Symbol font/0x67]2-C[Symbol font/0x67]3 would comprise instant SEQ ID NO:26 (SEQ ID NO:26 is the amino acid sequence of the heavy chain of the trastuzumab IgE plus IgG1 hinge-CH2-CH3, see the instant specification pages 36-37).
18. Claims 44, 49-56, 58-59, 60-63 and 66-69 are rejected under 35 U.S.C. 103 as being unpatentable over Kimes et al. (WO 2020/172473A1, pub date: 8/27/2020, effectively filed date: 2/20/2019), in view of Karagiannis et al. (Cancer Immunol Immunother, 2012, 61, 1547-1564, IDS filed on 7/28/2023), further in view of Kim et al. (Eur J Immunol., 1999, 29: 2819-2825).
The teachings of Kimes et al. and Karagiannis et al. have been set forth above as they apply to claims 44, 49-56, 58-59, 60-63, 65 and 68-69.
Regarding claims 66 and 67, Kimes et al. and Karagiannis et al. do not teach that the chimeric binding agent does not bind FcRn, and comprises a modified IgG CH2 and/or CH3 domain lacking one or more isoleucine or histidine residues associated with FcRn binding.
Kim et al. teaches that Ile253, His310 and His435 in human IgG1 play a central role in regulating serum half-life in mice and Fc-hinge fragments with mutation of Ile253, His310 and His435 have short persistence in the circulation, and also binds with very low affinity, if detectable, to recombinant soluble mouse FcRn (abstract and page 2822, Table 2). Kim et al. teaches that the interaction site of mouse FcRn on human and mouse IgG1 involves the same conserved amino acids located at the CH2-CH3 domain interface of the Ig molecule and the sequence similarities between mouse and human FcRn suggest that these studies have direct relevance to understanding the factors that govern the pharmacokinetics of therapeutic IgG (abstract).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Ile253, His310 and His435 in the IgG1 CH2-CH3 of the chimeric binding agent in view of Karagiannis and Kim. One of ordinary skill in the art would have been motivated to do so because Karagiannis et al. teaches that trastuzumab IgE has shorter serum half-life and longer tissue half-life compared to trastuzumab IgG, and IgE is a class of tissue-resident antibodies which can trigger powerful immune responses through strong affinity for their particular receptors on effector cells, and Hinton et al. teaches that Ile253, His310 and His435 play a central role in regulating serum half-life in mice and FC-hinge fragments with mutation of Ile253, His310 and His435 have short persistence in the circulation and bind with very low affinity to FcRn. One of ordinary skill in the art would have had a reasonable expectation of success because Kim et al. has shown that FC-hinge fragments with mutation of Ile253, His310 and His435 have short persistence in the circulation and bind with very low affinity to FcRn.
Applicant’s Arguments for 103 Rejections
The response states that the Office Communication concludes that "[i]t would have been obvious to combine the Fc region of IgE and the Fc region of IgG as suggested by Kimes because such combination would allow the antibody to kill tumor cells by different mechanisms." Office Communication at p. 23. This conclusion does not establish a prima facie case for at least three reasons.
First, as discussed in Section 2.3.1 above, Kimes teaches away from the activating-receptor architecture required by amended claim 44. Modifying Kimes to engage an activating Fc[Symbol font/0x67] receptor for cancer-cell killing would defeat the express anti-allergic, immunosuppressive purpose of the Kimes invention.
Second, Karagiannis itself does not "suggest" that an IgE-IgG hybrid would kill tumor cells by different mechanisms. Karagiannis discloses two separate molecules (trastuzumab IgE; trastuzumab IgG) that operate by different mechanisms; it does not suggest combining them into one bifunctional molecule. The Office Communication's articulation of motivation conflates two separate teachings (Kimes's IgE/IgG fusion architecture; Karagiannis's IgE/IgG comparison) and infers a motivation that neither reference, alone or in combination, actually provides. See In re Lee, 277 F.3d at 1344 (motivation to combine cannot be supported by conclusory statements).
Third, the Office Communication's invocation of In re Kerkhoven is inapposite for the reasons discussed in Section 2.3.1 above. Kimes (immunosuppression of allergic effector cells) and Karagiannis (cancer cell killing via either ADCC or ADCP) are not taught for the same purpose, and a Kerkhoven-style "logical combination" inference is not warranted.
Response to Arguments
Applicant’s arguments have been carefully considered but are not persuasive for the reasons discussed in the 102(a)(2) rejection and the following reasons. Kimes et al. teaches a chimeric binding agent comprising C[Symbol font/0x65]2-C[Symbol font/0x65]3-C[Symbol font/0x65]4-C[Symbol font/0x67]2-C[Symbol font/0x67]3, or C[Symbol font/0x67]2-C[Symbol font/0x67]3- C[Symbol font/0x65]2-C[Symbol font/0x65]3-C[Symbol font/0x65]4 domains (see [0071]), wherein the chimeric binding agent is capable of binding to Fc[Symbol font/0x67]Rs and Fc[Symbol font/0x65]Rs, wherein Fc[Symbol font/0x67]Rs include Fc[Symbol font/0x67]RI, Fc[Symbol font/0x67]RIIA, Fc[Symbol font/0x67]RIIIA and Fc[Symbol font/0x67]RIIIB (activating Fc[Symbol font/0x67] receptor), and Fc[Symbol font/0x65]Rs include Fc[Symbol font/0x65]RI and Fc[Symbol font/0x65]RII ([0072]). Kimes et al. teaches that the chimeric binding agent may further comprise a Fab ([0067]). Kimes et al. teaches that the chimeric binding agents may be fused to a molecule (e.g. a small molecule, a peptide, a polypeptide, or a protein) with targeting or homing function for a cell of interest or a target cell (e.g. an immune cell, or cancer cell) ([0090], [0136]).
Karagiannis et al. teaches that with a serum half-life of 21–24 days, compared to a half-life of 2–3 days in tissues, IgG antibodies may be the most effective antibody class to target blood-resident tumors and circulating tumor cells, while their ability to exert tumor surveillance in tissues may be less potent (p1548, last para). Karagiannis et al. teaches that the presence of IgE in the blood is short lived (half-life of 1.5 days), yet the half-life of IgE in tissues (2 weeks) is proportionately longer than that of IgG (2–3 days) (p1550, column 1). Karagiannis et al. compared trastuzumab IgE with trastuzumab IgG1 and found that trastuzumab IgE directed monocytic cells to kill tumor cells expressing the HER2/neu antigen by ADCC, a mechanism clearly different from ADCP employed by trastuzumab IgG and monocytic cells (p1555, column 2). The trastuzumab IgE comprises instant SEQ ID NOs 100-105, 1 and 160.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the chimeric binding agent of Kimes to comprise a Fab region of trastuzumab in view of Karagiannis. One of ordinary skill in the art would have been motivated to do so because Karagiannis et al. teaches that trastuzumab IgE directed monocytic cells to kill tumor cells expressing the HER2/neu antigen by ADCC, a mechanism clearly different from ADCP employed by trastuzumab IgG and monocytic cells (p1555, column 2), and the unique properties of IgE, a class of tissue-resident antibodies which can trigger powerful immune responses through strong affinity for their particular receptors on effector cells, could be employed for passive immunotherapy of solid tumors such as ovarian and breast carcinomas .
"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) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960).
In the instant case, both trastuzumab IgE and trastuzumab IgG were used in the prior art for killing cancer cells. It would have been obvious to link the Fab region of trastuzumab to the chimeric binding agent of Kimes (IgG-Fc-IgE-Fc) as suggested by Kimes because such combination would allow the antibody to kill tumor cells by different mechanisms.
One of ordinary skill in the art would have had a reasonable expectation of success because Kimes teaches a chimeric binding agent comprising a Fab, IgG Fc and IgE Fc, and Karagiannis et al teaches making trastuzumab IgE and has shown that trastuzumab IgE directed monocytic cells to kill tumor cells expressing the HER2/neu antigen by ADCC, a mechanism clearly different from ADCP employed by trastuzumab IgG and monocytic cells (p1555, column 2).
Conclusion
19. No claims are allowed.
20. Any inquiry concerning this communication or earlier communications from the examiner should be directed to HONG SANG whose telephone number is (571)272-8145. The examiner can normally be reached Monday-Friday 8am-5pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gregory Emch can be reached at 571-272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/HONG SANG/Primary Examiner, Art Unit 1646
Prosecution Insights