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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 25 August 2025 has been entered.
Status of the Claims
Claims 1-126 were originally filed on 19 March 2021. The preliminary amendment filed 19 March 2021 and 24 March 2021 have been entered and acknowledged. Claims 130-132 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 17 June 2024.
Claims 127, 128, 137, 142, 144, 145, 147, 148, 151, and 153 are under consideration.
Priority
The instant application claims priority to provisional application 62/734,771 filed 21 September 2018 and PCT application US2019/052396 filed 23 September 2019.
It is noted the provisional application does not disclose or contemplate all the limitations of the instant claim 137 which are drawn to synthetic binding agents with Seq ID Nos: 134 and 138. These sequences are not disclosed in the provisional application. Therefore, the instant application claim 137 will receive benefit of PCT/US2019 filed 23 September 2019.
Withdrawn Claim Rejections - 35 USC § 112
In view of Applicant’s arguments (i.e., motivation to combine) the following 35 USC 103 rejections
claims 127, 128, 137, 142, 144, and 151 over Miller (as cited on the PTO-892 dated 08/29/2024) and Young (as cited on the PTO-892 dated 08/29/2024) as evidence by Carter (as cited on the PTO-892 dated 08/29/2024),
claims 127, 128, 137, 142, 144, 148, and 151 over Miller, Wessler (as cited on the PTO-892 dated 08/29/2024), and in further view of Young, and
claims 144 and 145 are rejected under 35 U.S.C. 103 as being unpatentable over Miller, Young and Wang (see Wang et al. IgG Fc engineering to modulate antibody effector functions. Protein Cell 2018, 9(1):63–73),
claim 147 is rejected under 35 U.S.C. 103 as being unpatentable over Miller, Young, and Chen (see Chen et al. Fusion protein linkers: Property, design and functionality. Advanced Drug Delivery Reviews 65 (2013) 1357–1369),
claims 144 and 145 are rejected under 35 U.S.C. 103 as being unpatentable over Miller, Young, Wessler, and in further view of Wang, and
the following nonstatutory double patenting rejections
claims 127, 128, 142, 143, 148, and 151 are rejected over claims 1, 7, and 9 of U.S. Patent 12,115,219 B2 (previously referred to as copending Application No. 16/982682, referred to herein as ‘119 patent) in view of Miller and Wessler as evidenced by Racine and Winslow (see Racine and Winslow. IgM in microbial infections: taken for granted? Immunology Letters 125 (2009) 79–85),
claims 144 and 145 are rejected over claims 1, 7, and 9 of the ‘219 patent in view of Wessler, Miller, and Wang,
claim 147 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, and 9 of U.S. Patent 12,115,219 B2 (previously referred to as copending Application No. 16/982682, referred to herein as ‘119 patent) in view of Wessler, Miller, and Chen
are hereby withdrawn (see Response to Final received 08/25/2025, referred to herein as Remarks pg. 7, 3rd para).
In view of Applicant amendments to claims 127 regarding “the same epitope” in line 7 (i.e., antecedent basis and to clarify the synthetic binding agent binds specifically to RSV the 35 USC 112(b) rejection of claim 127 is hereby withdrawn.
Claim Interpretation
For the purposes of applying prior art, the claim scope has been interpreted as set forth below
per the guidance set forth in MPEP § 2111. If Applicant disputes any interpretation set forth below,
Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in
the subsequent response to the instant action. Applicant is advised that a specialized definition should
be properly supported and specifically identified (see, e.g., MPEP § (IV), describing how Applicant may
act as their own lexicographer).
Claim 127 is drawn to a synthetic binding agent comprising “a human or humanized Immunoglobulin G (IgG)” in lines 2-3. The specification does not provide a limiting definition for a human or humanized IgG; however several references to an Fc region are made throughout the specification and depicted in Figure 1 as an intact Fc region with no reference to Fc fragments (see specification pgs. 10-11 para [00040], pg. 36 para [000148], pg. 61 para [000223], figure 1A-G, figure 9). Therefore, a human or humanized IgG is interpreted as full length Fc region and antibodies with Fc fragments (i.e., one amino less than a full length Fc region) are not within the scope of claim 127. In addition, claim 127 is drawn to wherein “a pair of fragment antigen binding (fab)” in line 3 and “additional immunoglobulin Fab domains” in line 5 that all bind “a same epitope on RSV” lines 6-7. The specification does not provide a limiting definition for when an epitope is considered the same and when it is not. Therefore, “same” is given its plain and customary meaning and understood to mean all the Fab domains make physical contact with identical residues on RSV (see MPEP § 2111). Therefore, antibodies that make 1 or more/fewer physical contacts are not within the scope of claim 127.
Claim Objections
Claim 137 is objected to because of the following informalities:
Claim 137 recites, “comprising the amino acid sequences of: SEQ ID NO.:” in lines 3 and 4, and should recite, “comprising the amino acid sequence[[s]] of.
Appropriate correction is required.
Applicant is advised that should claim 127 be found allowable, claim 153 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 127, 128, 137, 142, 145-147, 151, and 153 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2009/018386 A1 (referred to herein as Wu) as evidenced by US Patent Publication 2006/0216284 A1 (referred to herein as Tous) and US Patent 6,818,216 B2 (referred to herein as Young2).
Wu discloses multispecific epitope binding proteins and their uses in prevention, management, treatment or diagnosis of acute or chronic diseases (see Wu abstract). In a particular embodiment, the structure comprises two Fab domains each linked to an additional 2 or more Fab domains and an antibody Fc region comprising a hinge CH2 and CH3 domain (see Wu Figure 4T, pg. 15 para [0056], pg. 72 para [0254], pg. 198 #18, 21, and 23). The domains of the multispecific epitope binding domains “may be separated by linker regions”, “such linker region may be flexible or rigid”, “in some embodiments the linker region orientation comprises sets of glycine repeats [Gly-Gly-Gly-Gly-Ser]x” (see Wu pg. 142 para [0156], pg. 43 para [0158]). In addition, Wu discloses a variety of recombinant methods have been developed for producing multiple epitope binding antibodies including those using two single chain Fv or Fab fragments with or without the use of flexible linkers (see Wu pg. 2 para [0008]). Wu discloses in particular embodiments “each epitope binding domain is specific for the same epitope” (see Wu pg. 4 para [0015], pg. 203 #63, pg. 204 #67, pg. 98 para [0320]). The epitope binding proteins are used “to inactivate various infectious agents”, in particular, RSV (see Wu pg. 110 para [0343], pg. 111 para [0344]). Furthermore, Wu discloses the claimed invention comprises at least one epitope selected from a group including RSV and RSV F protein (see Wu pg. 77 para [0269]). Wu teaches the epitope binding domain comprises or competes with motavizumab (see pg. 76 para [266, see line 19]).
Therefore, in the binding protein taught in Figure 4T of Wu, the ordinary artisan would have found it obvious to select RSV as a target antigen for each Fav using a known anti-RSV antibody (i.e., motavizumab, see claim 137) in order to treat/inactivate RSV as taught by Wu. There is a reasonable expectation of success given Wu engineered an antibody comprising two C5a epitope binding domains, anti-C5a 1B15 (Fab) and 15 (scFv), which retained binding affinity similar to the individual parental antibodies (see Wu pg. 186 para [0539], figure 4F). Regarding the claim language “that the synthetic binding agent binds to RSV and reduces an average mobility of the RSV in mucus to less than 50% relative to its native mobility in mucus”, this is a latent property of the multi-Fab construct in Wu. It is noted Wu discloses an identical structure including an IgG linked to an Fc domain, therefore mucotrapping is an inherent/latent property in Wu. This is pertinent to instant claims 127, 128, 151, and 153.
Regarding claim 137, motavizumab comprises instant Seq ID Nos: 134 and 138 as evidenced by Tous and Young2 Seq ID Nos: 254 and 255 (see Tous pg. 20, 2nd col. para [0221]; see Young2 col. 279, col. 283, Seq ID Nos: 254 and 255).
Regarding claim 142, Wu discloses the second Fab domain is connected to the first via the following:
1st polypeptide: (N terminus to C terminus) VH2-CH1-VL1-Ckappa/lambda
2nd polypeptide: (N terminus to C terminus) VL2-Ckappa/lambda-VH1-CH1-Fc (see Wu pg. 72 para [0254], figure 4T).
Regarding claims 145 and 146, Wu discloses the state of the art recognized variant of the Fc region can enhance or diminish effector function and teaches the multiepitope binding domains encompass said variants (see Wu pgs. 30-31 para [0116]). Furthermore, instantly claimed Seq ID No: 5 has 99.5% sequence identity with motavizumab as evidence by Tous and Young2 Seq ID Nos: 254 and 255 (see Tous pg. 20, 2nd col. para [0221]; see Young2 col. 279, col. 283, Seq ID Nos: 254 and 255; see sequence comparison below).
Regarding claim 147, Wu discloses the linker between domains comprises [Gly-Gly-Gly-Gly-Ser]x wherein X is a positive integer equal to or greater than 1 (see Wu pg. 43 para [0158]). In addition, Wu discloses the invention encompasses linkers between epitope binding domains of various lengths, in particular, comprising 15, 20, 25, 30, 35, and 40 amino acids (i.e., [Gly-Gly-Gly-Gly-Ser]x wherein X=3-8) (see Wu pg. 42 para [0158]).
Applicant's arguments filed 25 August 2025 (referred to herein as Remarks) have been fully considered but they are not persuasive.
Applicant argues no motivation to combine (see Remarks pg. 6 last para) and unexpected results (see Remarks pg. 9 1st para).
First, the new rejection set forth above teaches, “In some embodiments the epitope binding proteins of the invention may be used to inactivate RSV, hMPV, PIV, or influenza viruses” (see Wu pg. 110 lines 32-33).
Second, Applicant argues unexpected results in view of McLellan (see Remarks pg. 9, 1st para) and Applicant’s own work demonstrating improved pharmacokinetic data (see Declaration pg. 4, #8). Pursuant to MPEP § 716.02(e), an affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979). Applicant’s have submitted comparison of a Fab and IgG versions of the instantly claimed antibody in dependent claim 137 while the closest prior art discloses the instantly claimed structure (see Wu figure 4T). Therefore, Applicant’s have no compared the instantly claimed structure to the closest prior art. In addition, McLellan teaches neutralization potency was not effected in transitioning from 1-2 Fabs (see Remarks pg. 9, 2nd para). In particular, a neutralization assay wherein the motavizumab Fab and IgG structures have a nearly equivalent RSV neutralization potency (see McLellan Figure S6; see Declaration of Dr. Samuel Lai pursuant to 37 CFR 1.132 received 08/25/2025, referred to herein as Declaration, pg. 4, top). The state of the art at the time of filing teaches “neutralization is the ability of antibody to bind to and inactivate virus infectivity under defined conditions in vitro” and this particular property is effected by both the virion epitope and the antibody (see Reading and Dimmock (2007) Neutralization of animal virus infectivity by antibody. Arch Virol 152: 1047-1059, in particular summary). Factors that affect neutralization potency include the mechanisms of viral neutralization and pharmacokinetic properties of the antibody (see Reading and Dimmock summary, pg. 1048, 1st col. 1st para). It is also noted the latter is affected by both the primary amino acid sequence and the overall structure of the antibody (e.g., Fab vs IgG) (see Reading and Dimmock pg. 1056, 2nd col. 2nd para). Thus, an equivalent neutralization potency between the motavizumab Fab and IgG structures does not speak to the pharmacokinetic properties of the antibody (i.e., neutralization potency is not the same as ka, kd, and/or Kd). An equivalent neutralization would not dissuade the ordinary artisan from adding additional Fab domains to motavizumab. Reading and Dimmock teach, “most studies show that affinity probably does not have a profound effect on the level of neutralization but may be a determinant in target range for some viruses” (see Reading and Dimmock pg. 1056, 2nd para 1st full para). Wu discloses through a series of substitutions of palivizumab (i.e., the parent antibody of motavizumab) that increase kon were highly beneficial when converting from a Fab to an IgG while substitutions that increase koff were more beneficial for the Fab structure (see Wu et al. Ultra-potent antibodies against respiratory syncytial virus: effects of binding kinetics and binding valence on viral neutralization. J. Mol. Bio. (2005) 350, 126-144, referred to herein as Wu2 in particular pg. 139, 1st col. 1st para). Specifically, Wu2 discloses when Fab variants with over 100 fold higher koff values compared to palivizumab were converted to IgG molecules the difference in potency largely disappeared (see Wu para spanning pgs. 138-139). Wu2 also discloses “For full-length antibodies, kon maintains its influential role on IC50 while the impact of koff appears to much less” and “It should be noted however, that when kon has already been improved, additional substantial improvement in Koff may confer an added beneficial effect on IC50” (see Wu2 pg. 139, 2nd col 1st full para). Wu’s later work discloses motavizumab is a palivizumab derivative that has 11 fold increase in Koff and a 6 fold faster Kon (see Wu et al. Development of Motavizumab, an ultra-potent antibody for the prevention of respiratory syncytial virus infection in the upper and lower respiratory tract. J. Mol. Biol. 2007, 368, 652-665, referred to herein as Wu3, in particular pg. 659, 2nd col. 1st full para). Therefore, the ordinary artisan would not expect a change in neutralization potency in a motavizumab Fab compared to IgG given motavizumab has substitutions optimizing both the kon and koff wherein the kon was the pertinent variable in enhancing the neutralization of the parent antibody. Furthermore, the ordinary artisan would recognize that given the primary amino acid sequence had been optimized for both kon and koff increasing the number of binding domains would be an alternative method for further enhancing koff as evidenced by Goel (see Goel et al. Monoclonal antibody CC49:Improved biodistribution and potential for therapeutic application. Cancer Research 2000, Vol. 60, Iss. 24, 6964-6971, in particular pg. 6964, 2nd col. 2nd para), Fan (see Fan et al. Production of multivalent protein binders using a self-trimerizing collagen-like peptide scaffold. FASEB Journal 22: 3795-3804, in particular pg. 3795, 2nd col. 1st para), and Holliger and Hudson (see Holliger and Hudson. Engineered antibody fragments and the rise of single domains. Nature Biotechnology 2005. Vol. 23, No. 9, pgs. 1126-1136, in particular pg. 1128, 2nd col. 2nd para). Thus, McLellan would not dissuade the ordinary artisan from increasing the number of Fabs on motavizumab and Applicant’s allegedly unexpected results of a decrease in the lower unbinding rate (kd) is entirely expected given the state of the art. Applicant alleges, IN-002, was able to bind known antibody-resistant variants of RSV (see Declaration pg. 5 last para-pg. 6, 2nd para). However, the state of the art was such that increasing the valency of an antibody directed to a viral antigen could overcome viral escape (Hultberg et al. Llama-derived single domain antibodies to build multivalent super potent and broadened neutralizing anti-viral molecular. PLOS ONE 2011. Vol. 6, Iss. 4, pgs. 1-12, in particular pg. 2, 2nd col. last para, pg. 5, 1st col. 1st para, table 2). Specifically,
“A recent study using MAbs to the gp120 envelope protein of neutralization-sensitive and neutralization-resistant variants of simian immunodeficiency virus (SIV) showed that neutralization-insensitive virus bound Mabs with higher association rate constants than did neutralization-sensitive virus, but these MAbs also had higher dissociation rate constants [44]. This suggested that the interaction was unstable and provided an explanation for the neutralization-resistant phenotype. Affinity did not correlate with neutralization for the MAbs tested” (see Reading and Dimmock pg. 1056, 2nd col. 2nd para).
Thus Applicant’s own work demonstrates stabilizing binding to escape variants through modification of koff (e.g., increasing valency) is in line with prior art, stating “IN-002 exhibited significantly higher affinity (approximately 10 fold better) than motavizumab, primarily driven by its lower dissociation rate constant (kd) (i.e., koff), which indicates prolonged binding stability to RSV F-protein (see Declaration pg. 5, 1st para).
Applicant’s arguments regarding the flexibility of the linkers is supported by post filing art (i.e., 2022) while the instant application has a priority date of 2018. Therefore, Yermak was not available to the ordinary artisan at the time of filing (see Yermak et al. as cited on the IDS received 02/25/2025; see Remarks 11, bottom half of middle para). Furthermore, the prior art structure is identical to the claimed structure, and any properties regarding mucotrapping that relate to wingspan or flexible linkers would be inherent/latent properties in the prior art, not unexpected results.
Applicant’s argue the size discrepancy between the VHH (approximately 17 kDa) as a trimer binding to RSV F protein suggests the ordinary artisan would not expect the tread in improving koff with additional antigen binding domains of a VHH to be observed with larger binding domains (i.e., “One of ordinary skill in the art would not presume that binding of the trivalent nanobodies would predict binding by full-sized human/humanized IgG to RSV, much less binding by IgG having additional Fab domains”) (see Declaration pg. 6 last para; see Remarks pg. 10, 1st para). As previously stated Detalle, demonstrates increasing the number of binding domains is effective in improving koff, wherein Nb017 is the single VHH and ALX-0171 is trivalent (see Detalle Table 1; reproduced below).
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Fan demonstrates a similar trend in an erb scFv collabody wherein the erb_scFv is approximately 28kD, the erb_scFv-Fc (i.e., IgG format) is approximately 110 kD, and the erb_scFv-Col (i.e., trivalent) is approximately 120kD, showed consistent improvement in koff (see Fan figure 1; reproduces below). It is noted the erb_scFv binds the EGFR-ECD which is approximately 70 kD (see Gonzalez-Magaldi et al. Structure and organization of full-length epidermal growth factor receptor in extracellular vesicles by cryo-electron tomography. PNAS 2025 Vol. 122 No. 23, pgs. 1-12, e2424678122, in particular abstract) .
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Lastly, Applicant’s allegedly unexpected results are not commensurate in scope with the instant claims (see MPEP § 716.02(d)). Applicant’s allegedly unexpected results are drawn to an IgG antibody with the structure set forth in figure 1B comprising a particular number of motavizumab antigen binding domains arrange in a particular order, a particular Fc region (i.e., sequence, glycosylation pattern), and a particular flexible amino acid linker, while the instant claims are drawn to any RSV antigen binding domain will at least four or more Fab domains that all bind the same RSV epitope with any flexible amino acid linker and any Fc region.
Claims 127 and 144 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2009/018386 A1 (referred to herein as Wu) and Zhao (see Zhao et al. 2017. Discovery of a perfusion respiratory syncytial virus F-specific monoclonal antibody that provides greater in vivo protection than the murine precursor of palivizumab. J Virol 91:e00176-17) as evidenced by US Patent Publication 2006/0216284 A1 (referred to herein as Tous) and US Patent 6,818,216 B2 (referred to herein as Young2).
The reasons claim 127 is obvious over Wu as evidenced by Tous and Young2 are set forth above.
Briefly Wu discloses multiepitope binding proteins wherein the structure comprises multiple epitope binding domains specific for the same epitope and suggests motavizumab as an epitope binding domain (see Wu figure 4N, 4P, 4R, and 4T; see above).
Zhao discloses motavizumab has 13 amino acid substitutions from the parent palivizumab resulting in increased affinity and an 18-fold higher neutralization potency (see Zhao pg. 2, 3rd para). In addition, palivizumab is a humanized antibody on a human IgG1 framework (see Zhao pg. 2, 1st para).
Therefore, an ordinary artisan in modifying the structure taught by Wu (i.e., 4T) to comprise the epitope binding domain of motavizumab would also use the IgG1 Fc region given it is part of the motavizumab structure. This is pertinent to claim 144.
Claims 148 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2009/018386 A1 (referred to herein as Wu) and Smith (see Smith et al. (2016) Antigen nature and complexity influence human antibody light chain usage and specificity. Vaccine, 34(25): 2813-2820).
The teachings of Wu are set forth above.
Briefly Wu discloses in Figure 4T and IgG molecule with 4 Fab domains linked to an Fc region. In addition, Wu discloses targeting RSV and the use of flexible linkers between domains wherein the structure is able to inactivate the virus.
Smith discloses lambda and kappa light chains are different and complementary to each other (see Smith pg. 10 last para). Monoclonal antibodies generated to different serotypes of Streptococcus pneumoniae used either kappa or lambda light chains (see Smith pg. 7, 2nd para). Previous work indicates 15% of kappa containing monoclonal antibodies are cross reactive to two serotypes no while lambda light chains demonstrated different cross-reactivities and “none were the same as the kappa containing antibodies” (see Smith pg. 7 last para). For example, Smith discloses antibodies PVAX4-p7B03 and PVAX5-p4A05 bind to 19A and rather than binding the related 19F serotype the antibodies bind the unrelated serotype 9V (see Smith pg. 7 last para). Smith suggests the data indicates that lambda chain antibodies act as a second compartment of specificities to broaden the repertoire and its usage is different and complementary to the kappa response (see Smith pg. 9, 2nd para).
Therefore an ordinary artisan would select both lambda and kappa light chain antibodies that bind the same RSV epitope in order to capture the advantages of either light chain regarding affinity and cross reactivity.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 127, 128, 137, 142, 143, 145-148, 151, and 153 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, and 9 of U.S. Patent 12,115,219 B2 (referred to herein as ‘219 patent) and Wu.
The ‘219 patent claims a nebulized solution for treating RSV comprising an antibody comprising a human or humanized Fc region with a particular glycosylation pattern (see ‘219 claim 1), wherein the antibody is IgG (see ‘219 claim 7), in particular motavizumab (see ‘219 claim 9).
The teachings of Wu are set forth above.
Therefore the ordinary artisan would modify the motavizumab as claimed in the ‘219 patent with the structure taught by Wu (i.e., figure 4T) given Wu discloses the invention encompasses structures that comprise motavizumab (as claimed in the ‘219 patent) to inactivate RSV.
Claims 144 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, and 9 of U.S. Patent 12,115,219 B2 (previously referred to as copending Application No. 16/982682, referred to herein as ‘119 patent), Wu, and Zhao.
The reasons claim 127 are obvious over the ‘219 patent and Wu are set forth above.
The teachings of Zhao are set forth above.
Therefore the ordinary artisan in using motavizumab would inherently be using a naturally occurring Fc region as taught by Zhao.
Claims 127, 128, 137, 142, 143, 145-148, 151, and 153 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 29, 35, and 37 of copending Application No. 18/884822 (referred to herein as ‘822 application) in view of Wu.
The ‘822 application claims a nebulized solution for treating RSV comprising an antibody comprising a human or humanized Fc region with a particular glycosylation pattern (see ‘822 claim 29), wherein the antibody is IgG (see ‘822 claim 35), in particular motavizumab (see ‘822 claim 37).
The teachings of Wu are set forth above.
Therefore the ordinary artisan would modify the motavizumab as claimed in the ‘219 patent with the structure taught by Wu (i.e., figure 4T) given Wu discloses the invention encompasses structures that target the same epitope and comprise motavizumab (as claimed in the ‘822 application) to inactivate RSV.
This is a provisional nonstatutory double patenting rejection.
Claims 144 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 29, 35, and 37 of copending Application No. 18/884,822 (referred to herein as ‘822 application) in view of Wu, and Zhao.
The reasons claim 127 are obvious over the ‘822 application and Wu are set forth above.
The teachings of Zhao are set forth above.
Therefore the ordinary artisan in using motavizumab would inherently be using a naturally occurring Fc region as taught by Zhao.
This is a provisional nonstatutory double patenting rejection.
Claims 127, 128, 137, 142, 144-148, 151, and 152 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 35, 58, 65, and 66 of copending Application No. 18/869,268 (referred to herein as ‘268 application).
The ‘268 application claims a method of treating a subject having a respiratory disorder, in particular RSV (see ‘268 application claim 35 and 58) comprising administering to the subject a formulation comprising a therapeutic human IgG monoclonal antibody with a particular glycosylation pattern at a particular dose (see ‘268 application claim 35, 65, and 66). In performing the NSDP analysis, the first question to be asked is whether any examined claim is either anticipated by, or obvious over, a claim in the copending application (see MPEP § 804 (II)(B), second paragraph). While normally one cannot look into the specification of that copending application, it is in fact appropriate to learn which particular embodiments the claims cover (see MPEP § 804(II)(B)(1)). The ‘267 application states,
“in particular, the drug agents described herein may include drug agents that are trapped within mucus, as described, e.g., in each of US 10,829,543, US 10,100,102, US 10,793,623, U.S. patent application no 16/982,682 (titled "COMPOSITIONS AND METHODS FOR INHIBITING PATHOGEN INFECTION" and filed 3/20/2019), U.S. patent application no. 35 17/063,122 (titled "OPTIMIZED CROSSLINKERS FOR TRAPPING A TARGET ON A SUBSTRATE" and filed 10/5/2020), and U.S. patent application no. 17/278,217 (titled “SYNTHETIC BINDING AGENTS FOR LIMITING PERMEATION THROUGH MUCUS" and filed Sep 23, 2019), each of which is herein incorporated by reference in its entirety.” (see specification pgs. 23-24 para [0084]).
The ‘267 application is intended to administer the product instantly claimed and a method of treating a subject necessarily anticipates the product to be administered.
This is a provisional nonstatutory double patenting rejection.
Claims 127, 128, 137, 142, 144-148, 151, and 152 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8, and 9 of copending Application No. 17/889,141 (referred to herein as ‘141 application).
The ‘141 application claims a method of delivering nebulized particles of a drug agent to a patient’s nasal passages via a nebulizer (see ‘141 claim 1), wherein the drug agent is a recombinant antibody comprising a particular glycosylation pattern (see ‘141 claim 8) and a human or humanized Fc region with the property of enhancing the trapping potency of the recombinant antibody (see ‘141 claim 9). In performing the NSDP analysis, the first question to be asked is whether any examined claim is either anticipated by, or obvious over, a claim in the copending application (see MPEP § 804 (II)(B), second paragraph). While normally one cannot look into the specification of that copending application, it is in fact appropriate to learn which particular embodiments the claims cover (see MPEP § 804(II)(B)(1)). The ‘267 application states,
“in particular, the drug agents described herein may include drug agents that are trapped within mucus, as described, e.g., in each of US 10,829,543, US 10,100,102, US 10,793,623, U.S. patent application no 16/982,682 (titled "COMPOSITIONS AND METHODS FOR INHIBITING PATHOGEN INFECTION" and filed 3/20/2019), U.S. patent application no. 35 17/063,122 (titled "OPTIMIZED CROSSLINKERS FOR TRAPPING A TARGET ON A SUBSTRATE" and filed 10/5/2020), and U.S. patent application no. 17/278,217 (titled “SYNTHETIC BINDING AGENTS FOR LIMITING PERMEATION THROUGH MUCUS" and filed Sep 23, 2019), each of which is herein incorporated by reference in its entirety.” (see specification pg. 17 para [0063]).
The ‘141 application is intended to administer the product instantly claimed and a method of treating a subject necessarily anticipates the product to be administered.
This is a provisional nonstatutory double patenting rejection.
Claim Rejections - 35 USC § 112(b)
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.
Claims 127, 128, 137, 142, 144-148, 151, and 153 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 127 is drawn to a human or humanized Immunoglobulin G (IgG) (lines 2-3) having a pair of fragment antigen binding (Fab) domains, wherein each Fab domain of the human or humanized IgG is linked to an additional immunoglobulin Fab domains (lines 4-5). The scope of the additional immunoglobulin Fab domains in lines 4-5 is unclear. For example, is each Fab domain of the human or humanized IgG linked to a single additional Fab domain as “an additional” is singular for a minimum of 3 Fab domains, or alternatively, is each Fab domain of the pair of Fab domains linked to a separate additional Fab domain as “additional Fab domains” is plural for a minimum of 4 Fab domains. To put another way is the pair of Fab domains both linked to a single additional Fab domain or is the first Fab of the pair of Fabs linked to a first additional Fab domain and the second Fab of the pair of Fabs linked to a second additional Fab domain wherein all the Fab domains bind an identical RSV epitope.
Claims 127 and 148 also recites the limitation "the IgG Fab domains" in line 6 (claim 127) and line 1 (claim 148). There is insufficient antecedent basis for this limitation in the claim. Claim 127 recites both “human or humanized IgG” (lines 2-3) and “additional immunoglobulin Fab domains” (lines 4-5). In addition, it is unclear if the human or humanized IgG recited in lines 2-3 encompasses the pair of Fab domains, Fc region, the flexible amino acid linker, and the additional Fab domains or alternatively if the human or humanized IgG is limited to a pair of Fab domains and Fc region.
Claims 127, 128, 137, 142, 147, 148 recites the limitation “the additional Fab domains” in lines 5-6 (claim 127) and lines 1-2 (claim 128).
Claim 127 is drawn to wherein the synthetic binding agent reduces an average mobility of the RSV in mucus to less than 50% relative to its native mobility in mucus. The scope of “native mobility” is unclear. For example, when is the mobility considered native and when is it not. To put another way, does “native mobility” encompass wherein naturally occurring structures (e.g., naturally occurring antibodies, cells) are bound to RSV or alternatively is “native mobility” limited unbound RSV in mucus. In addition, the scope of “mucus” is unclear. Specifically, is the mucus recited in the clause, “the reduction in average mobility of the RSV in mucus” the same mucus as “its native mobility in mucus”. For example, is a synthetic binding agent with an average mobility in lung mucus that is half the value of the unbound RSV in cervical mucus within the scope of claim 127 or alternatively are the two recitations intended to be the same mucus.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 128 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. In so far as claim 127 is intended to require each Fab domain of the pair of Fab domains be linked to an additional Fab domain wherein a first Fab of the pair of Fab domains is linked to a first additional Fab domain and wherein a second Fab of the pair of Fab domains is linked to a second additional Fab domain for a minimum of four Fab domains and in so far as “the additional Fab domains” is intended to refer to “an additional immunoglobulin Fab domains” in lines 4-5 of claim 127 then claim 128 does not further limit claim 127. Claim 128 id drawn to wherein the additional Fab domains comprises 2 which is a total of 4 already required by claim 127.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Sequence Comparison
(Qy) Instant Seq ID No: 5 v Young2 Seq ID No. 254
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371
532
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Conclusion
No claim allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US Patent Publication 2018/0057598 A1 published March 1st 2018 (referred to herein as Lazar) reduces to practice tetravalent monoepitopic IgG antibodies (see figure 3A). For example, Drozitumab IgG1 had modest activity while the tetravalent monoepitopic format had intrinsic agonist activity (see Lazar pg. 124 para [0917]). In addition Lazar teaches the tetravalent monoepitopic structure can be used to target RSV.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/H.A.P./Examiner, Art Unit 1644
/AMY E JUEDES/Primary Examiner, Art Unit 1644