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 .
DETAILED ACTION
Claims 3, 5, and 12-25 are pending and under consideration.
Priority
It is acknowledged that this application is a 371 of Internation Application No. PCT/CN2022/111998 filed August 12, 2022, which claims the benefit of priority to PCT patent Application No. PCT/CN2021/112372 filed August 13, 2021. The priority date for the pending claims has been established as August 13, 2021
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
The Information Disclosure Statement filed on 02/06/2024 has been considered and entered by examiner.
Claim Objections
Claim 19 is objected to because of the following informalities: “the nucleic acid molecule of claim 18” should be “the isolated nucleic acid molecule of claim 18” for clarity. Appropriate correction is required.
Claim 20 is objected to because of the following informalities: “the nucleic acid molecule of claim 18” should be “the isolated nucleic acid molecule of claim 18” for clarity. Appropriate correction is required.
Claim 21 is objected to because of the following informalities: “the host cell of claim 20” should be “the isolated host cell of claim 20” for clarity. Appropriate correction is required.
Claim 22 is objected to because of the following informalities: “the anti-FcRn antibody according to claim 3” should be “the isolated anti-FcRn antibody according to claim 3” for clarity. Appropriate correction is required.
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.
Claims 5, 16 and 17 are 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.
The independent claim (claim 3) requires specific, fixed CDR sequences for VH and VL of the claimed antibody. However, the dependent claim (claim 5) attempts to encompasses a broad 80% sequence identity to the entire VH and VL region. Because “80% sequence identity” allows variations across the variable domain, this variant could mutate the highly specific CDRs defined in the independent claim. If a variant antibody falls into the 80% identity bucket but loses the recited CDR sequences, the dependent claim (claim 5) would effectively be broader than or inconsistent with the independent claim (claim 3).
Claim 16 is dependent on claim 3 and recites “wherein the anti-FcRn antibody is chimeric, human, or humanized”. However, each of CDRs of claim 3 is CDRs of an antibody obtained by immunizing a mouse, whereas a human antibody means that all parts thereof (including CDRs) are derived from human. Thus, claim 16 failed to include all the limitations of the claim 3 and broaden the scope of claim 3.
Claim 17 is dependent on claim 3 and recites “wherein the anti-FcRn antibody is an antigen binding fragment selected from the group consisting of a …, a Fd, or a doabody”. Fd represents only the heavy chain component of the Fab fragment (consisting of the Vh and CH1 domains) and lacks the entire light chain. However, claim 3 recites an anti-FcRn antibody comprising both HC-CDRs: 1-3 and LC-CDRs: 1-3. Thus, claim 17 failed to include all the limitations of the claim 3 and broaden the scope of claim 3.
Applicant may cancel the claims, amend the claims to place the claims in proper dependent form, rewrite the claims in independent form, or present a sufficient showing that the dependent claims complies with the statutory requirements.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 23-25 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for
“a method of treating a disease or condition in an individual in need thereof, comprising administering to the individual an effective amount of the pharmaceutical composition of claim 22, wherein the disease or condition is a IgG mediated autoimmune disorder or IgG mediated inflammatory diseases”,
does not reasonably provide enablement for
“a method of treating a disease or condition in an individual in need thereof, comprising administering to the individual an effective amount of the pharmaceutical composition of claim 22”.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to the invention commensurate in scope with these claims. This is a SCOPE of ENABLEMENT rejection.
To be enabling, the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir.,1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996).
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547, the court recited eight factors to consider when assessing whether or not a disclosure would require undue experimentation. These factors are:
1) the quantity of experimentation necessary, 2) the amount of direction or guidance provided, 3) the presence or absence of working examples, 4) the nature of the invention 5) the state of the art, 6) the relative skill of those in the art, 7) the predictability of the art and 8) the breadth of the claims.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108,427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
Nature of invention and breadth of the claims:
Claim 23 is drawn to a method of treating a disease or condition in an individual in need thereof. The claim does not limit the claimed” disease or condition”. Thus, given Broadest Reasonable Interpretation (BRI), the claim encompasses unlimited diseases or conditions, which may or may not associated with IgG.
Relative skill in the art:
The relative skill of those in the art is high with an MD or a PhD.
Level of unpredictability in the art and State of the prior art:
Regarding FcRN and FcRN inhibitors, Yang (Yang et al., Front Immunol., 16: 1656937, Publication Date: 10/02/2025) teaches that the neonatal Fragment Crystallizable receptor (FcRn) plays a central role in maintaining immunoglobulin (Ig) G homeostasis by protecting IgG from lysosomal degradation and regulating its transcytosis. Pharmacological inhibition of FcRn has emerged as a promising therapeutic strategy for IgG-mediated autoimmune diseases. By accelerating the catabolism of circulating IgG, FcRn inhibitors (including anti-FcRN antibodies) effectively reduced pathogenic autoantibody levels without broadly suppressing other immune components (see Abstract). However, as evidenced by Zhang (Zhang et al., J cell Immunol., 2025; 7(6): 263-267, Publication Year: 2025), some autoimmune diseases are not associated with IgG (Abstract). In contrast to classical antibody-mediated autoimmunity disease, cellular-mediated disease is characterized by delayed-type hypersensitivity reactivations in which autoreactive T cells orchestrate inflammation and induce direct tissue destruction (see 1st paragraph of Introduction). Autoimmune diseases primarily mediated by cellular immunity include diabetes mellitus, multiple sclerosis (MS), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD) (see 1st paragraph of Introduction). Thus, one of ordinary skill int the art could not predict that the claimed pharmaceutical composition would be able to treat a broad genus of diseases and conditions encompassed by the claim, e.g. diseases or conditions not associated with pathogenic IgG.
Direction or guidance and working examples:
The working example of the specification discloses that chimeric anti-FcRN antibody ZLP193 and humanized anti-FcRN antibodies ZLP1-3-2M and ZLP1-3-2F were able to decrease human IgG rapidly in mice after intravenous injection (Example 7 and Fig. 11). However, the working examples do not support the scope of the claims: all diseases and conditions encompassed by claims 23-25. In particular, the specification and prior art do not support treating diseases or conditions not associated with/mediated by IgG with the claimed pharmaceutical compositions comprising the claimed anti-FcRN antibody.
The quantity of experimentation needed:
The factors outlined in In Re Wands' mentioned above apply here, and in particular as per the MPEP 2164.01 (a): "A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)." It is very clear that one could not make/use this very broad invention that has no working examples in this unpredictable art without undue experimentation. Genetech Inc vs Nova Nordisk 42 USPQ 2d 1001 "A patent is not a hunting license. It is not a reward for search but compensation for its successful conclusion and patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable.”
Given the numerous unspecified antibodies or antibody fragments and diseases/conditions encompassed by these claims, the lack of specific guidance and the insufficient working examples, undue experimentation would be required of one of skilled in the art to produce the invention commensurate with the scope of the method as claimed.
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 3, 5, 12-16, and 22-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/996,786 (hereinafter Appl. 786). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The claims of Appl. 786 teach a high-concentration antibody formulation, wherein the antibody formulation comprises a monoclonal antibody and surfactants, wherein the surfactants are polysorbate and poloxamer, and the concentration of the monoclonal antibody is from 100mg/ml to 200mg/ml, optionally from 135mg/ml to 165mg/ml (claim 1); wherein the antibody is am anti-FcRN antibody (claim 17); wherein the anti-FcRN antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 5; and a VL comprising the amino acid sequence of SEQ ID NO:6;… (claim 19). As shown below, SEQ ID NO: 5 and SEQ ID NO; 6 of Appl. 786 are identical to SEQ ID NO:51 and SEQ ID NO: 61 of instant application (antibody ZLP1-3-2M, see Table 3B of instant specification), respectively:
SEQ ID NO: 5 vs. SEQ ID NO: 51:
US-18-681-232-51
Query Match 100.0%; Score 634; DB 1; Length 118;
Best Local Similarity 100.0%;
Matches 118; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLQESGPGLVKPSETLSLTCTVTGYSFTSGYSWHWIRQPPGKGLEWIGYIHDSGGTNY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLQESGPGLVKPSETLSLTCTVTGYSFTSGYSWHWIRQPPGKGLEWIGYIHDSGGTNY 60
Qy 61 NPSLKSRVTISRDTSKNQFSLKLSSVTAADTAVYYCAREENYRYFDVWGQGTLVTVSS 118
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NPSLKSRVTISRDTSKNQFSLKLSSVTAADTAVYYCAREENYRYFDVWGQGTLVTVSS 118
SEQ ID NO: 6 vs. SEQ ID NO: 61:
US-18-681-232-61
Query Match 100.0%; Score 545; DB 1; Length 106;
Best Local Similarity 100.0%;
Matches 106; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EIVLTQSPATLSLSPGERATLSCSASSSVSYMHWFQQKPGQSPRLLIYSTSNLASGIPAR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EIVLTQSPATLSLSPGERATLSCSASSSVSYMHWFQQKPGQSPRLLIYSTSNLASGIPAR 60
Qy 61 FSGSGSGTDFTLTISSLEPEDFAVYYCQQRSSYPPTFGQGTKVEIK 106
||||||||||||||||||||||||||||||||||||||||||||||
Db 61 FSGSGSGTDFTLTISSLEPEDFAVYYCQQRSSYPPTFGQGTKVEIK 106
Thus, the antibody of claims of Appl. 786 reads on the antibodies of instant claims 3, 5.
Regarding instant claim 12, as evidenced by the instant specification, the antibody would have the same Kd (4.93E-10 M) as ZLP1-3-2M described in Table 11 of the instant specification.
Regarding instant claim 13-15, as evidenced by the specification of Appl. 786, The “antibody” of the present application includes full-length antibodies (which would comprise an Fc fragment) and antigen binding fragments. The antibodies can be IgG1, IgG2, IgG3 (see page 7, para. 2). The “antigen-binding fragment” would include a diabody, a Fab, a Fab’, an Fv fragment, scFv (see page 7, para. 3).
Regarding instant claim 16, as evidenced by Example 6 of the instant specification, ZLP1-3-2M is a humanized antibody.
Regarding instant claims 22-24, the claims of Appl. 786 teach the use of the antibody formulation of claim 1 in the preparation of medicament for the treatment of diseases; optionally, the diseases include inflammatory or autoimmune diseases. Thus, the formulation comprising the antibody would read on the instant claim 22.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 18-21 and 25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-20 of copending Application No. 18/996,786 (hereinafter Appl. 786), as applied to claims 3, 5, 12-16, and 22-24, further in view of Blumberg (Blumberg et al., US 2020/0181262 A1, Publication Date: 06/11/2020).
The claims of Appl. 786 teach the instant claims 3 and 23 as set forth above. However, the claims of Appl. 786 do not teach an isolated nucleic acid molecule encodes the antibody, a vector comprising the isolated nucleic acid molecule, a host cell comprising the vector, a method of producing the antibody, or a method treating a disease of claim 25.
Blumberg teaches recombinant antibodies to FcRn and the method of treating autoimmune disorders (Abstract).
Blumberg teaches that FcRn regulates serum IgG concentrations by binding to and protecting endocytosed monomeric IgG from degradation in the lysosomal compartment ([0004]).
Blumberg teaches various anti-FcRn antibodies ([0013]-[0020]).
Blumberg teaches an isolated nucleic acid encoding an FcRn antibody or antigen-binding fragment described herein. Also provided herein is a nucleic acid vector comprising an isolated nucleic acid encoding an FcRn antibody or antigen-binding fragment described herein. Also provided herein is a prokaryotic or eukaryotic host cell comprising an isolated nucleic acid encoding an FcRn antibody or antigen-binding fragment described herein ([0044], [0160], [0164]).
Blumberg teaches a method for the production of an antibody capable of binding the Fc-binding region of FcRn, said method comprising: (a) culturing a host cell as described above; and (b) isolating said antibody from the host cell or the culture medium of the host cell ([0166]). Humanized anti-FcRn antibodies has been successfully produced by expressing antibodies in a host cell and purified by Protein A sepharose (see Example 1, [0279]).
It would have prima facie been obvious to one of ordinarily skilled in the art before the effective filing date of the claimed invention to combine the teachings of the claims of Appl. 786 and Blumberg, and to produce the antibody taught by the claims of Appl. 786 with the method of Blumberg, because the method has been well-known and has successfully produced isolated anti-FcRn antibodies. One of ordinary skill in the art would have had a reasonable expectation that the method would be effective to produce the antibodies of Appl. 786.
Regarding claim 25, Blumberg teaches that anti-FcRn antibodies can be used to treat autoimmune disease such as myasthenia gravis (MG) ([0225], claim 7). It would have prima facie been obvious to one of ordinarily skilled in the art before the effective filing date of the claimed invention to treat an autoimmune disease as taught by the claims of Appl. 786, and to treat specific autoimmune disease: myasthenia gravis (MG) as taught by Blumberg. One of ordinary skill in the art would have had a reasonable expectation of success because Blumberg teaches that anti-FcRn antibodies can be used for myasthenia gravis (MG). The motivation would have been to apply to the antibody to a suitable patient population.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHENG LU whose telephone number is (571)272-0334. The examiner can normally be reached Monday-Friday 8-5.
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/CHENG LU/Examiner, Art Unit 1642
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642
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