DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The claim listing filed December 27, 2022 is pending.
Claims 1-46 are pending.
Election/Restriction
Applicant’s election of Group III (claims 40-44, drawn to methods of treating a disease caused by a function of human TLR7); and the species of:
(a) anti-TLR7 antibody comprising:
(i) CDRH1-3 and CDRL1-3 as SEQ ID NOs: 17-22, respectively;
(ii) a VH and VL pair as SEQ ID NOs: 5 and 11, respectively;
(iii) a heavy and light chain pair as amino acid sequence as positions 20-465 in SEQ ID NO: 35 and amino acid sequence as positions 21-233 in SEQ ID NO: 36, respectively;
(iv) a humanized VH and VL pair as SEQ ID NOs: 42 and 44, respectively;
(v) a humanized heavy and light chain pair as amino acid sequence as positions 20- 465 in SEQ ID NO: 46 and amino acid sequence as positions 21-233 in SEQ ID NO: 49, respectively; and
(vi) an antibody modification as a deletion of one or two amino acids at the carboxyl terminus of the heavy chain;
(c) additional pharmaceutical product as an anti-inflammatory drug;
(d) ailment to treat as an immune inflammation-related disease; and
(e) immune inflammation-related disease as systemic lupus erythematosus
in the reply filed on November 25, 2025 is acknowledged.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-39, 45, and 46 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions.
Claims 40-44 are currently under consideration.
Claims 40 and 41 are independent claims.
Priority
The present application is a CON of 17/366,820 (PAT 11,578,138) filed on 07/02/2021 which is a CON of 17/069,760 (PAT 11,091, 560) filed 10/13/2020 which is a CIP of PCT/JP2019/021466 filed 05/30/2019. The present Application also claims foreign priority to JP2018-104676 filed 05/31/2018.
The Examiner acknowledges the receipt of a certified copy of JP2018-104676 on 04/26/2023, in language other than English, as required by 37 CFR 1.55.
The Applicant is invited to submit certified translations of PCT/JP2019/02146 and JP2018-104676 to clarify the record.
Claim Rejections - 35 USC § 112
Indefinite Language
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 40-44 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 pre-AIA the applicant regards as the invention.
Claims 40 and 41 recite the limitation “[a] method for treating a disease caused by a function of human TLR7” in lines 1 and 2. Dependent claims 42-44 recite that the disease is “an immune inflammation-related disease” (claim 42), “wherein the immune inflammation-related disease is systemic lupus erythematosus, rheumatoid arthritis, juvenile idiopathic arthritis, adult-onset Still's disease, ankylosing spondylitis, systemic scleroderma, polymyositis, dermatomyositis, psoriatic arthritis, osteoarthritis, mixed connective tissue disease or muscular dystrophy” (claims 43 and 44).
The asserted/recited causation of the claimed diseases with a function of human TLR7 renders the claims indefinite because these limitations are ambiguous and unclear.
For example, it is unclear if the limitation of “treating a disease caused by a function of human TLR7” reads on the breadth of the claimed diseases or if it reads on subsets of diseases based on a function of human TLR7.
While the expression of TLR7 may be associated with the inflammation associated with various diseases, TLR7 does not necessarily cause the disease. Further, the role of TLR7 in inflammation is associated with various pathways, molecules (e.g., cytokines, interferons, etc.) and cells. The role of TLR7 in inflammation is not based upon TLR7 only.
While targeting TLR7 in the treatment of various diseases is warranted, the role of TLR7 in various diseases is different from causing the disease. For example, infectious diseases are disorders caused by organisms, such as bacteria, viruses fungi or parasites; cancer is complex group of disease with many possible causes and the exact cause of autoimmune diseases are unknown.
Thus, one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the invention.
The Applicant is invited to consider amending the claims to recite modes of action in inhibiting TLR7 functions as the intended use of the pharmaceutical compositions
Applicant should specifically point out the support for any amendments made to the disclosure. See MPEP 714.02 and 2163.06.
Written Description
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 40-44 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim 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 instant claims are drawn to methods for treating a disease caused by a function of human TLR7 comprising administering at least one of antibody or an antigen-binding fragment of the antibody having the properties of: (a) specifically binding to human TLR7 or monkey TLR7 and not binding to mouse TLR7 or rat TLR7; and (b) inhibiting a function of human TLR7 or monkey TLR7.
To support such anti-TLR7 antibodies, the instant specification discloses three murine anti-human TLR7 antibodies: AT01 antibody (comprises CDRH1-3 and CDRL1-3 as SEQ ID NOs: 17-22, respectively); the NB7 antibody (comprises CDRH1-3 and CDRL1-3 as SEQ ID NOs: 23-28, respectively); and the FAN2 antibody (comprises CDRH1-3 and CDRL1-3 as SEQ ID NOs: 29-34, respectively) (e.g. see page 108, [0145] and pages 156 and 157). The specification also discloses the VH and VL of these antibodies (e.g. see pages 155 and 156).
The AT01, NB7, and FAN2 antibodies specifically bind to human and monkey TLR7 but they do not bind to mouse or rat TLR7 (e.g. see [0160]).
The specification also discloses that the AT01, NB7, and FAN2 antibodies were used create chimeric murine/human anti-human TLR7 antibodies (e.g. see Example 4, [0176]). Humanized versions of the AT01 and NB7 antibodies (huATOl_H1L1l_IgGlLALA, huATO1_H3L1_IgGlLALA, huATOl_H3L2_IgGlLALA, huATO01_H3L2_IgG4Pro, huNB7_H3L3_IgGlLALA, and huNB7_H3L3_IgG4Pro) were also made (e.g. see [0231]).
When given the broadest reasonable interpretation in light of specification, the anti-TLR7 antibody of the instant invention is defined broadly to be any anti-TLR7 antibody that can bind to and inhibit human and monkey TLR7 but does not bind to or inhibit mouse or rat TLR7.
It is noted that none of the claims recite any structure for the antibody.
The guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, § 1 "Written Description" Requirement make clear that if a claimed genus does not show actual reduction to practice for a representative number of species, then the Requirement may be alternatively met by reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus (Federal Register, Vol. 66, No. 4, pages 1099-1111, January 5, 2001, see especially page 1106 column 3). In The Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412) 19 F. 3d 1559, the court held that disclosure of a single member of a genus (rat insulin) did not provide adequate written support for the claimed genus (all mammalian insulins). In this same case, the court also noted:
“A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is. See Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen). It is only a definition of a useful result rather than a definition of what achieves that result. Many such genes may achieve that result. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”). Accordingly, naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material.”
Artisans are well aware that knowledge of a given antigen (for instance TLR7) provides no information concerning the sequence/structure of antibodies that bind the given antigen. For example, Edwards et al. (J. Mol. Biol., 2003, 334:103-118) teach that over 1,000 different antibodies to a single protein can be generated, all with different sequences spanning almost the entire heavy and light chain germline repertoire (42/49 functional heavy chain germlines and 33 of 70 V-lambda and V-kappa light chain germlines, and with extensive diversity in the HCDR3 region sequences (that are generated by VDJ germline segment recombination) as well, see entire document).
As such, it does not seem possible to predict the sequence/structure of an antibody that binds a given antigen, as there does not appear to be any common or core structure present within all antibodies that gives rise to the function of antigen binding. Further, given data, such as that of Edwards et al., indicating the diversity of sequences in a population of antibodies that bind to a given antigen, no number of species appears to reasonably representative of the breadth of the genus of antibodies that bind the given antigen.
It should be pointed out that it is well established in the art that the formation of an intact antigen-binding site requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three different complementarity determining regions, CDR1, 2 and 3, which provide the majority of the contact residues for the binding of the antibody to its target epitope. 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 parent immunoglobulin (Janeway Jr et al., Immunology, 3rd Edition, 1997 Garland Publishing Inc., pages 3:1-3:11.see entire selection).
Thus, based upon the prior art, skilled artisans would reasonably understand that it is the structure of the CDRs within an antibody which gives rise to the functional property of antigen binding, the epitope to which said CDRs bind is an inherent property which appears to necessarily be present due to conservation of critical structural elements, namely the CDR sequences themselves.
This applies to the instant invention which is drawn to a genus of anti-TLR7 antibodies that encompasses those bind to and inhibit human and monkey TLR7 but do not bind to or inhibit mouse or rabbit TLR7.
As noted above, the specification discloses three murine anti-human TLR7 antibodies: the AT01 antibody, the NB7 antibody, and the FAN2 antibody all of which specifically bind to human and monkey TLR7 but do not bind to mouse or rat TLR7. It is noted that these antibodies were also used to generate chimeric and humanized antibodies which still comprise the CDRs of the murine parent antibodies. However, such a disclosure does not serve to provide sufficient written description of the claimed genus of anti-TLR7 antibodies. Further, the disclosure does not identify any specific structural features or combination of features which give rise to the function of binding to human and monkey TLR7 and no binding to mouse and rat TLR7. Additionally, there does not appear to be any reasonable shared structure present in the genus of recited anti-TLR7 antibodies which gives rise to their functional activity. Ultimately, identifying an antibody simply on the basis of what it binds rather than by identifying the sequence/structure, namely the CDRs, of the antibody in question is generally insufficient to provide written description of the antibody in question.
There is insufficient written description for the breadth anti-TLR7 antibodies as currently claimed, which are distinct and diverse and do not share a common structure that contributes to a common ability to bind to human and monkey TLR7 but not bind to mouse and rat TLR7.
Therefore, in view of the breadth of the claims and the limited disclosure, artisans would reasonably conclude that applicant was not in possession of the full breadth of anti-TLR7 antibodies encompassed by the claims at the time the instant application was filed.
Amending the claims to recite the CDRs of the AT01, NB7, and FAN2 antibodies would obviate this part of the rejection.
Enablement
Claims 40-44 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The factors considered in determining whether a disclosure would require undue experimentation include:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 8 USPQ2d, 1400 (CAFC 1988) and MPEP § 2164.01.
Nature of the invention/Breadth of the claims
Independent claims 40 and 41 are drawn to methods for treating any disease caused by any function, including normal function or dysfunction, of human TLR7 comprising administering at least one of antibody or an antigen-binding fragment of the antibody having the properties of: (a) specifically binding to human TLR7 or monkey TLR7 and not binding to mouse TLR7 or rat TLR7; and (b) inhibiting a function of human TLR7 or monkey TLR7.
Dependent claim 42 limits the disease to any immune inflammation-related disease.
Dependent claims 43 and 44 limit the immune inflammation-related disease to systemic lupus erythematosus.
State of the prior art/Predictability of the art
While the expression of TLR7 may be associated with the inflammation associated with various diseases, TLR7 does not necessarily cause disease. Further, the role of TLR7 in inflammation is associated with various pathways, molecules (e.g., cytokines, interferons, etc.) and cells. The role of TLR7 in inflammation is not based upon TLR7 only.
While targeting TLR7 in the treatment of various diseases is warranted, the role of TLR7 in various diseases is different from causing the disease. For example, infectious diseases are disorders caused by organisms, such as bacteria, viruses fungi or parasites; cancer is complex group of disease with many possible causes and the exact cause of autoimmune diseases are unknown. Thus, while TLR7 plays a role in these diseases, including inflammatory diseases, they are not caused by TLR7 solely.
It is noted that there are some systemic autoimmune diseases where enhanced TLR7 signaling contributes to disease (e.g. see Brown et al. 2022. Nature. 605, 349-356, Abstract). This is particularly evident in systemic lupus erythematosus (SLE) where a TLR7 gain-of-function variant was found to cause the disease. TLR7 is a sensor of viral RNA and binds to guanosine. The identified missense TLR7Y264H variant selectively increased sensing of guanosine and 2',3'-cGMP and was sufficient to cause lupus when introduced into mice. Brown et al. teach that enhanced TLR7 signaling drives aberrant survival of B cell receptor (BCR)-activated B cells, and in a cell-intrinsic manner, accumulation of CD11c+ age-associated B cells and germinal center B cells (e.g. see Brown et al. 2022. Nature. 605, 349-356, Abstract).
Thus, one of ordinary skill in the art would conclude that, at most, diseases that are “caused” by a TLR7 function would be limited to those caused by TLR7 dysfunction such as systemic autoimmune diseases, including SLE.
Working examples/ Guidance in the specification
While the binding selectivity of the murine (e.g. see Example 2) and chimeric antibodies (e.g. see Example 5) were evaluated in vitro; and the inhibitory activity of the humanized antibodies on cytokine (IL-6) production were evaluated in vitro (e.g. see Example 7) and in vivo (e.g. see Example 9); the Applicant has not provided any working examples for a method of treating a disease, let alone an immune inflammation-related disease or SLE, with an anti-TLR7 antibody.
The Applicant includes immune inflammation-related diseases, allergic diseases, infections, and cancers as diseases caused by a function of TLR7 (e.g. see [0104]). The Example has also included a long list of specific disease for each of these types of disease (e.g. see [0105] – [0108]).
Amount of experimentation necessary
The instant specification fails to disclose any working examples for a method of treating a disease, let alone an immune inflammation-related disease or SLE, with an anti-TLR7 antibody. Thus, based on the content of the disclosure in view of the prior art, which limits TLR7 function-causing diseases to those caused by TLR7 dysfunction such as systemic autoimmune diseases, including SLE, a skilled artisan, through extensive trial-and-error experimentation, would have to identify diseases caused by any TLR7 function (normal or abnormal) and treat them with an anti-TLR7 antibody with a reasonable expectation of success. This quantity of experimentation goes beyond what is considered “a reasonable degree of experimentation” and constitutes undue further experimentation in order to enable the claimed method of treating.
Thus, the specification does not enable one of ordinary skill in the art to use what is claimed and therefore claims 40-44 are rejected under 35 U.S.C. 112(a), enablement.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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 40-44 are rejected under 35 U.S.C. 103 as being unpatentable over Miyake et al. 2016 (US 20160185871 A1, an IDS reference filed 12/27/2022) in view of Chang et al. 2016 (US 20160361360 A1) and Kuhn et al. 2015 (Dtsch Arztebl Int. 112: 423–32).
Independent claim 40 is drawn to a method for treating a disease caused by a function of human TLR7 comprising administering at least one of antibody or an antigen-binding fragment of the antibody having the properties of: (a) specifically binding to human TLR7 or monkey TLR7 and not binding to mouse TLR7 or rat TLR7; and (b) inhibiting a function of human TLR7 or monkey TLR7.
Independent claim 41 is drawn to a method for treating a disease caused by a function of human TLR7 comprising administering at least one of antibody or an antigen-binding fragment of in combination with an anti-inflammatory drug, wherein the antibody has the properties of: (a) specifically binding to human TLR7 or monkey TLR7 and not binding to mouse TLR7 or rat TLR7; and (b) inhibiting a function of human TLR7 or monkey TLR7.
Dependent claim 42 limits the disease in claim 40 to any immune inflammation-related disease.
Dependent claims 43 and 44 limit the immune inflammation-related disease in claim 42 to systemic lupus erythematosus.
Regarding claims 40-42, Miyake et al. teach a therapeutic agent or preventive for an inflammatory disease comprising an anti-TLR7 antibody (e.g. see claim 1) wherein the inflammatory disease is an autoimmune disease (e.g. see claim 14), and, regarding claims 43 and 44,wherein the autoimmune disease is systemic lupus erythematosus (e.g. see claim 15).
Further regarding claims 40 and 41, Miyake et al. also teach that their invention embraces a method of treating or preventing autoimmune diseases including a step of administering the antibody of the present invention to a subject (e.g. see [0238]). Specifically, the inhibitory effect of the anti-TLR7 monoclonal antibody was studied using mice suffering from a TLR7-dependent inflammatory disease (e.g. see [0284]). Unc93b1.sup.D34A/D34A mice in which the 34-th aspartic acid of Unc93b1 gene has been substituted with alanine has systemic lethal inflammation due to hyperreaction of TLR7 (e.g. see [0284]). The anti-TLR7 monoclonal antibody was administered by injection to Unc93b1.sup.D34A/D34A mice (e.g. see [0285]). The results show that the anti-TLR7 antibody improves TLR7-dependent systemic inflammation of Unc93b1.sup.D34A/D34A mice (e.g. see [0286]).
Regarding claims 40 and 41, Miyake et al. do not teach that their anti-TLR7 antibody binds to human TLR7 or monkey TLR7 and does not bind to mouse TLR7 or rat TLR7. Additionally, regarding claim 41, Miyake et al. do not teach that their anti-TLR7 antibody is administered in combination with an anti-inflammatory drug.
Chang et al. teach that a person of ordinary skill will realize that for human therapeutic use, antibodies that bind to human antigens, as opposed to their animal homologs, are preferred.
Kuhn et al. teach that all patients with systemic lupus erythematosus (SLE), a disease caused by TLR7 dysfunction, should be treated with antimalarials, in particular hydroxychloroquine, an anti-inflammatory drug, as soon as the diagnosis is confirmed (e.g. see summary, results). Hydroxychloroquine is associated with a higher rate of remission, fewer relapses, and reduced damage in the course of the disease (e.g. see summary, results).
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 Miyake et al. to incorporate the teachings of Chang et al. and Kuhn et al. to include that the anti-TLR7 antibody binds to human TLR7 or monkey TLR7 and does not bind to mouse TLR7 or rat TLR7 and that the anti-TLR7 antibody is administered in combination with an anti-inflammatory drug
Given that for human therapeutic use, antibodies that bind to human antigens, as opposed to their animal homologs, are preferred (Chang et al.); it would have been obvious to a skilled artisan, with the goal of treating a disease caused by TLR7 in a human subject, to experiment with substituting Miyake et al.’s anti-mouse TLR7 antibody with an anti-human TLR7 antibody that does not bind to mouse TLR7 with a reasonable expectation of success.
Furthermore, given that hydroxychloroquine, an anti-inflammatory drug, is always the first line of treatment for SLE, a disease caused by TLR7 dysfunction and the higher rate of remission, fewer relapses, and reduced damage in the course of the disease associated with hydroxychloroquine (Kuhn et al); it would have been obvious to a skilled artisan, with the goal of treating SLE, to experiment with using Miyake et al.’s anti-TLR7 antibody in combination with hydroxychloroquine with a reasonable expectation of success.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
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 40-44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 11,091,560 (the ‘560 Patent, an IDS reference filed 12/27/2022) in view of Kuhn et al. 2015 (Dtsch Arztebl Int. 112: 423–32).
Independent claim 40 is drawn to method for treating a disease caused by a function of human TLR7, comprising administering at least one antibody or an antigen-binding fragment of, the antibody having the properties of: (a) specifically binding to human TLR7 or monkey TLR7 and not binding to mouse TLR7 or rat TLR7; and (b) inhibiting a function of human TLR7 or monkey TLR7.
Independent claim 41 is also drawn to method for treating a disease caused by a function of human TLR7, wherein the anti-TLR7 antibody is administered together with an anti-inflammatory drug.
Dependent claim 42, limits the disease caused by a function of human TLR7 in claim 40 to an immune inflammation-related disease.
Dependent claims 43 and 44, limit the immune inflammation-related disease to systemic lupus erythematosus.
The claims in the ‘560 Patent are drawn to an antibody or an antigen-binding fragment of the antibody having the properties of: (a) specifically binding to human TLR7 or monkey TLR7 and not binding to mouse TLR7 or rat TLR7; (b) inhibiting a function of human TLR7 or monkey TLR7; and (c) comprising CDRH1-3 and CDRL1-3 as SEQ ID NOs: 17-22; and a pharmaceutical composition comprising the anti-TLR7 antibody.
The anti-TLR7 antibody or antigen-binding fragment thereof of the ‘560 Patent is a species encompassed by the instantly claimed genus of anti-TLR7 antibodies or antigen-binding fragments thereof. It is noted that a nonstatutory double patenting rejection is appropriate when the claim being examined is, for example, generic to a species or sub-genus claimed in a conflicting patent or application, i.e., the entire scope of the reference claim falls within the scope of the examined claim. In such a situation, a later patent to a genus would, necessarily, extend the right to exclude granted by an earlier patent directed to a species or sub-genus. In this type of nonstatutory double patenting situation, an obviousness analysis is not required for the nonstatutory double patenting rejection. See MPEP 804.II.B.2.
Thus, the instantly claimed genus of anti-TLR7 antibodies is anticipated by the species claimed in the ‘560 Patent.
The reference claims differ from the instant invention by not reciting that the antibodies are used in a method of for treating a disease caused by a function of human TLR7, wherein the disease is an immune inflammation-related disease, or wherein the disease is systemic lupus erythematosus; or that the antibodies are used in combination with an anti-inflammatory drug in a method of for treating a disease caused by a function of human TLR7.
It is noted that in Geneva Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F.3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003), the court applied nonstatutory double patenting to invalidate a claim without analyzing anticipation or obviousness. The earlier patent claimed a compound and the written description disclosed a single utility of that compound as administration to a human in amounts effective for inhibiting ß-lactamase. The later patent claimed nothing more than the earlier patent’s disclosed utility as a method of using the compound. Thus, the court found that the claims of the later patent and the claims of the earlier patent were not patentably distinct. The Geneva court relied on equitable principles, not an obviousness-type analysis, in reaching its conclusion. Id. at 1386, 68 USPQ2d at 1875 (quoting In re Byck, 48 F.2d 665, 666 (CCPA 1931)). See MPEP 804.II.B.6.
This applies to the instant case where the specification of the ‘560 Patent discloses that their claimed antibody can be used in: (a) a method for treating a disease caused by a function of human TLR7 (e.g. see column 12, lines 1-5); and (b) combination with an anti-inflammatory drug in a method for treating a disease caused by a function of human TLR7 (e.g. see column 12, lines 6-13). The specification of the ‘560 Patent also discloses that the disease caused by a function of human TLR7 is an immune inflammation-related disease (e.g. see column 12, lines 14-17) and that the immune inflammation-related disease is systemic lupus erythematosus (e.g. see column 12, lines 18-27).
Thus, the instant claims are nothing more than a disclosed utility of the anti-TLR7 antibody of the ‘560 Patent and therefore the claims are not patentably distinct.
Regarding instant claim 41, the ‘560 Patent does not teach that their anti-TLR7 antibody is administered in combination with an anti-inflammatory drug.
The teachings of Kuhn et al. are outlined in the 103 rejection above.
It would be obvious to one of ordinary skill in the art to modify the ‘560 Patent to incorporate the teachings of Kuhn et al. to include that the anti-TLR7 antibody is administered in combination with an anti-inflammatory drug
Given that hydroxychloroquine, an anti-inflammatory drug, is always the first line of treatment for SLE, a disease caused by TLR7 dysfunction and the higher rate of remission, fewer relapses, and reduced damage in the course of the disease associated with hydroxychloroquine (Kuhn et al); it would be obvious to a skilled artisan, with the goal of treating SLE, to experiment with using the ‘560 Patent’s anti-TLR7 antibody in combination with hydroxychloroquine with a reasonable expectation of success.
As such, the claims in the ‘560 Patent would render the instant claims obvious.
Claims 40-44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-39 of U.S. Patent No. 11,578,138 (the ‘138 Patent) in view of Kuhn et al. 2015 (Dtsch Arztebl Int. 112: 423–32).
Independent claim 40 is drawn to method for treating a disease caused by a function of human TLR7, comprising administering at least one antibody or an antigen-binding fragment of, the antibody having the properties of: (a) specifically binding to human TLR7 or monkey TLR7 and not binding to mouse TLR7 or rat TLR7; and (b) inhibiting a function of human TLR7 or monkey TLR7.
Independent claim 41 is also drawn to method for treating a disease caused by a function of human TLR7, wherein the anti-TLR7 antibody is administered together with an anti-inflammatory drug.
Dependent claim 42, limits the disease caused by a function of human TLR7 in claim 40 to an immune inflammation-related disease.
Dependent claims 43 and 44, limit the immune inflammation-related disease to systemic lupus erythematosus.
The claims in the ‘138 Patent are drawn to a polynucleotides comprising a polynucleotide sequence encoding an antibody or an antigen-binding fragment of, the antibody having the properties of: (a) specifically binding to human TLR7 or monkey TLR7 and not binding to mouse TLR7 or rat TLR7; (b) inhibiting a function of human TLR7 or monkey TLR7; and (c) comprising CDRH1-3 and CDRL1-3 as SEQ ID NOs: 17-22; expression vectors; host cells; methods for producing the antibody or antigen-binding fragment thereof.
It is noted that obtaining cDNA / nucleic acids from protein sequences has been routine and conventional in the art and used to make proteins of interest, including antibodies of interest. For example, expression vectors can comprise polynucleotides sequences encoding amino acids, in turn antibodies (e.g., anti-TLR7 antibodies). Given that obtaining cDNA / nucleic acids from protein sequence sequences is routine and conventional, it would have been obvious to the ordinary artisan to obtaining cDNA to produce proteins of interest.
This applies to the instant case where it would be obvious to a skilled artisan to obtain the anti-TLR7 antibody or antigen-binding fragment thereof from the polynucleotide of the ‘138 Patent.
Thus, it is noted that the obviously obtained anti-TLR7 antibody or antigen-binding fragment thereof of the ‘138 Patent is a species encompassed by the instantly claimed genus of anti-TLR7 antibodies or antigen-binding fragments thereof. It is noted that a nonstatutory double patenting rejection is appropriate when the claim being examined is, for example, generic to a species or sub-genus claimed in a conflicting patent or application, i.e., the entire scope of the reference claim falls within the scope of the examined claim. In such a situation, a later patent to a genus would, necessarily, extend the right to exclude granted by an earlier patent directed to a species or sub-genus. In this type of nonstatutory double patenting situation, an obviousness analysis is not required for the nonstatutory double patenting rejection. See MPEP 804.II.B.2.
Thus, the instantly claimed genus of anti-TLR7 antibodies is anticipated by the species claimed in the ‘138 Patent.
Regarding the claims drawn to methods for producing the antibody or antigen-binding fragment thereof, it is noted that product defined by the process by which it can be made is still a product claim (In re Bridgeford, 357 F.2d 679, 149 USPQ 55 (CCPA 1966)). See MPEP 806.05(f).
The reference claims differ from the instant invention by not reciting that the antibodies are used in a method of for treating a disease caused by a function of human TLR7, wherein the disease is an immune inflammation-related disease, or wherein the disease is systemic lupus erythematosus; or that the antibodies are used in combination with an anti-inflammatory drug in a method of for treating a disease caused by a function of human TLR7.
It is noted that in Geneva Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F.3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003), the court applied nonstatutory double patenting to invalidate a claim without analyzing anticipation or obviousness. The earlier patent claimed a compound and the written description disclosed a single utility of that compound as administration to a human in amounts effective for inhibiting ß-lactamase. The later patent claimed nothing more than the earlier patent’s disclosed utility as a method of using the compound. Thus, the court found that the claims of the later patent and the claims of the earlier patent were not patentably distinct. The Geneva court relied on equitable principles, not an obviousness-type analysis, in reaching its conclusion. Id. at 1386, 68 USPQ2d at 1875 (quoting In re Byck, 48 F.2d 665, 666 (CCPA 1931)). See MPEP 804.II.B.6.
This applies to the instant case where the specification of the ‘138 Patent discloses that their claimed antibody can be used in: (a) a method for treating a disease caused by a function of human TLR7 (e.g. see column 12, lines 12-16); and (b) combination with an anti-inflammatory drug in a method for treating a disease caused by a function of human TLR7 (e.g. see column 12, lines 17-24). The specification of the ‘138 Patent also discloses that the disease caused by a function of human TLR7 is an immune inflammation-related disease (e.g. see column 12, lines 25-28) and that the immune inflammation-related disease is systemic lupus erythematosus (e.g. see column 12, lines 29-38).
Thus, the instant claims are nothing more than a disclosed utility of the anti-TLR7 antibody of the ‘138 Patent and therefore the claims are not patentably distinct.
Regarding instant claim 41, the ‘138 Patent does not teach that their anti-TLR7 antibody is administered in combination with an anti-inflammatory drug.
The teachings of Kuhn et al. are outlined in the 103 rejection above.
It would be obvious to one of ordinary skill in the art to modify the ‘138 Patent to incorporate the teachings of Kuhn et al. to include that the anti-TLR7 antibody is administered in combination with an anti-inflammatory drug
Given that hydroxychloroquine, an anti-inflammatory drug, is always the first line of treatment for SLE, a disease caused by TLR7 dysfunction and the higher rate of remission, fewer relapses, and reduced damage in the course of the disease associated with hydroxychloroquine (Kuhn et al); it would be obvious to a skilled artisan, with the goal of treating SLE, to experiment with using the ‘138 Patent’s anti-TLR7 antibody in combination with hydroxychloroquine with a reasonable expectation of success.
As such, the claims in the ‘560 Patent would render the instant claims obvious.
Claims 40-44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-6 of U.S. Patent No. 10,370,451 (the ‘451 Patent, corresponds to IDS reference US Pat. Pub. 20160185871 filed 12/27/2022) in view of Chang et al. 2016 (US 20160361360 A1) and Kuhn et al. 2015 (Dtsch Arztebl Int. 112: 423–32).
Independent claim 40 is drawn to method for treating a disease caused by a function of human TLR7, comprising administering at least one antibody or an antigen-binding fragment of, the antibody having the properties of: (a) specifically binding to human TLR7 or monkey TLR7 and not binding to mouse TLR7 or rat TLR7; and (b) inhibiting a function of human TLR7 or monkey TLR7.
Independent claim 41 is also drawn to method for treating a disease caused by a function of human TLR7, wherein the anti-TLR7 antibody is administered together with an anti-inflammatory drug.
Dependent claim 42, limits the disease caused by a function of human TLR7 in claim 40 to an immune inflammation-related disease.
Dependent claims 43 and 44, limit the immune inflammation-related disease to systemic lupus erythematosus.
The claims in the ‘451 Patent are drawn to method of treating a TLR7-dependent inflammatory disease comprising a step of administering a therapeutic agent to a subject, the therapeutic agent comprising an anti-TLR7 (anti-Toll-like receptor 7) antibody according to claim 1.
It is noted that the CDRs recited in claim 1 refer to the A94B10 antibody which is an anti-mouse TLR7 antibody.
Regarding instant claims 40 and 41, the ‘451 Patent does not teach that their anti-TLR7 antibody binds to human TLR7 or monkey TLR7 and does not bind to mouse TLR7 or rat TLR7. Additionally, regarding instant claim 41, the ‘451 Patent does not teach that their anti-TLR7 antibody is administered in combination with an anti-inflammatory drug.
The teachings of Chang et al. and Kuhn et al. are outlined in the 103 rejection above.
It would be obvious to one of ordinary skill in the art to modify the ‘451 Patent to incorporate the teachings of Chang et al. and Kuhn et al. to include that the anti-TLR7 antibody binds to human TLR7 or monkey TLR7 and does not bind to mouse TLR7 or rat TLR7 and that the anti-TLR7 antibody is administered in combination with an anti-inflammatory drug
Given that for human therapeutic use, antibodies that bind to human antigens, as opposed to their animal homologs, are preferred (Chang et al.); it would be obvious to a skilled artisan, with the goal of treating a disease caused by TLR7 in a human subject, to experiment with substituting the ‘451 Patent’s anti-mouse TLR7 antibody with an anti-human TLR7 antibody that does not bind to mouse TLR7 with a reasonable expectation of success.
Furthermore, given that hydroxychloroquine, an anti-inflammatory drug, is always the first line of treatment for SLE, a disease caused by TLR7 dysfunction and the higher rate of remission, fewer relapses, and reduced damage in the course of the disease associated with hydroxychloroquine (Kuhn et al); it would be obvious to a skilled artisan, with the goal of treating SLE, to experiment with using the ‘451 Patent’s anti-TLR7 antibody in combination with hydroxychloroquine with a reasonable expectation of success.
As such, the claims in the ‘451 Patent would render the instant claims obvious.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Grace H. Lunde whose telephone number is (703)756-1851. The examiner can normally be reached Monday - Thursday 5:00 a.m. - 3:00 p.m. (EST).
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, Misook Yu can be reached at (571) 272-0839. 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.
/GRACE H LUNDE/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641