DETAILED ACTION
Applicant’s amendment and response received on 11/3/25 has been entered. Claim 36 has been canceled, and new claims 64-70 have been added. Claims 26-35, 37, 52, and 54-70 are now pending in this application.
Applicant’s election of Group II, claims 27, 35, 37, and 52, drawn to antiserum or antibodies which recognize a Kexin peptide and methods of administering said antiserum or antibodies to a patient to treat or prevent aspergillosis, without traverse, is acknowledged.
Claims 26, 28, 30, and 54-63 are hereby withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/3/25. Claims 27, 29, 31-35, 37, 52, and 64-70 as amended now read on the elected invention and are therefore currently under examination. An action on the merits follows.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 5/13/22 and 10/10/22 are in compliance with the provisions of 37 CFR 1.97 and 1.98. Accordingly, the information disclosure statements have been considered by the examiner, and initialed and signed copies of the 1449s are attached to this action.
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 26-35, 37, 52, and 54-70 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 26-35, 37, and 54-70 are drawn to methods of preventing or treating aspergillus infection, aspergillosis, or conditions associated with aspergillus infection either in an immunosuppressed or non-immunosuppressed patient by administering an antiserum produced against an Aspergillus Kexin peptide, or an isolated and purified antibody produced against an Aspergillus Kexin peptide. The claim also include a product claim, claim 52, drawn to an isolated antiserum. Antiserum is defined in the specification refers to a blood serum that contains one or more antibodies, i.e. polyclonal antibodies, directed against a specific antigen, in this case an Aspergillus Kexin peptide. An “isolated or purified antibody” as defined by the specification encompasses monoclonal antibodies and fragments thereof including scFv, and humanized or human antibodies.
Given the broadest reasonable interpretation, the claims embrace an extremely large genus of polyclonal and monoclonal antibodies and their derivatives solely defined by their function- binding to an Aspergillus Kexin peptide. Note as well that with the exception of claim 37, which recites a specific Aspergillus fumigatus Kexin peptide with the amino acid sequence of SEQ ID NO:2 or SEQ ID NO:3, which only differ by 2 flanking amino acids, the claims read broadly on antiserum and antibodies that recognize and bind to a large genus of Aspergillus Kexin peptides, including full length Kexin polypeptides and peptides of any length derived from Kexin polypeptides from any species of Aspergillus, of which there are several hundred. Claims 31 and 66 limits the species of Aspergillus to 6 specific species, and claims 32 and 67 limit the species to Aspergillus fumigatus. Thus, the claims as a whole encompass potentially millions of different antibodies whose only shared feature is binding to one of several hundred different Aspergillus kexin polypeptides, or thousands of Aspergillus kexin peptides derived therefrom.
The specification fails to provide an adequate disclosure for the genus of antiserum or antibodies, and in particular monoclonal or polyclonal antibodies or fragments thereof that are capable of binding to any Aspergillus kexin peptide, including the Aspergillus fumigatus peptides set forth as SEQ ID NOS: 2 and 3. The specification fails provide sufficient description for the broad genus of antibodies encompassed by the claims in terms of distinguishing characteristics of the genus and in particular the structure properties of an antibody that define binding to any Aspergillus kexin peptide, such as heavy or light chain sequences, and in particular heavy and light chains CDR sequences, and further fails to provide sufficient description for antibodies that bind to Aspergillus kexin peptide and are capable of exhibiting a therapeutic effect on any species of Aspergillus infection or aspergillosis in a subject. The specification broadly discloses that anti-kexin antiserum can be generated by administering an Aspergillus kexin peptide to a subject. The specification also refers to the general knowledge in the art for standard procedures for obtaining antibodies including monoclonal antibodies, such as isolation of antibodies directly from the blood or the use of hybridomas. However, despite teaching that standard procedures are available to obtain antibodies and monoclonal antibodies, the specification does not actually describe any antibody which is capable of binding to any Aspergillus kexin peptide from any species of Aspergillus, and which further exhibits the functional property of having a therapeutic effect on Aspergillus infection or Aspergillosis in a subject.
Turning to the working examples, in example 5, the specification teaches that a recombinant AF.KEX1 peptide with the sequence of SEQ ID NO:2 was used to immunize immunocompetent mice, and that plasma obtained from the mouse post-immunization contained antibodies which recognized the AF.KEX1 peptide in vitro. However, the working examples do provide any structural or sequence information regarding any of the antibodies which may be present in the plasma and which are capable of binding to the peptide of SEQ ID NO:2. Further, the working examples do not provide any functional information for any single antibody or combination of antibodies present in the polyclonal serum in regards to binding characteristics, such as binding affinity to SEQ ID NO:3, or the specificity of the binding of any antibody to SEQ ID NO:3 versus other peptides, including potential cross-reactivity with other Aspergillus fumigatus kexin peptides, or other species of Aspergillus kexins. It is also noted that the working examples do not include any examples of the administration of any antiserum or antibody to any subject. Thus, as whole, the specification, including the working examples, fails to provide any specific description of any antibody in terms of physical characteristics such as sequence or structure which is capable of binding any Aspergillus kexin peptide, let alone polyclonal or monoclonal antibodies capable of having a therapeutic effect in vivo on Aspergillus infection or associated conditions in a subject.
Combinatorial diversity and somatic mutation during B cell development and maturation into antibody secreting cells contribute to the diversity of antibodies which are capable of recognizing a particular antigen epitope such that it is unlikely that any two antibodies which recognize the same antigen, or even antigen epitope would share the same amino acid or nucleic acid sequence. At the time of filing, the art teaches that antibody specificity and binding to antigen epitopes is largely determined by complementarity determining regions (CDRs). There are 6 CDRs produced by the pairing of heavy and light chain variable regions in an intact antibody. While the heavy chain CDR3 region has been implicated as being crucial for defining antigen specificity of an antibody, the art teaches that both CDRs and framework regions (FRs) in the heavy and light chain also contribute to and affect antigen specificity and affinity. The prior art at the time of filing does not teach any specific antibody binding motif or domain shared among all antibodies which bind to a specific antigen, nor does the prior art at the time of filing teach that specific residues at specific positions in the antibody heavy chain or light chain are either essential or non-essential to the binding of any and all antibodies. Instead, the prior art at the time of filing is replete with teachings that while the overall structure between antibodies is shared, the structure of the antigen binding region of an antibody and the residues involved in binding to its cognate antigen are unique to each antibody and can involve residues both within any one or all of the heavy and light chain CDRs and framework regions (see for example, Vajdos et al. (2002) J. Mol. Biol., Vol. 320, 415-428, Chen et al. (1992) J. Exp. Med., Vol. 176, 855-866, and Sela-Culang et al. (2013) Frontiers in Immunology, Vol. 4, pages 1-13). Vajdos et al. teaches that residues in both the CDRs and framework regions of antibodies can be important for antigen recognition and binding, and discloses attempts to identify key residues in the antigen binding site of the Fab2C4 antibody for its peptide epitope derived from the extracellular domain of the human oncogene ErbB2 (Vajdos et al., pages 416-418). Vajdos et al. teaches that two different mutagenesis strategies were used to identify key residues in peptide binding- shotgun alanine scanning mutagenesis and shotgun homolog-scanning mutagenesis- and report that the results of the two methods in combination three dimensional crystal structure of the Fab2C4 antibody provided distinct yet complementary view of key residues in binding between the antibody and antigen (Vajdos et al., page 417, Figure 1 and Table 2). As can be seen in Figure 1, each method identified different key residues, with some overlap. Vajdos et al. states that key residues for binding are present in both the heavy and light chain and include both solvent exposed and buried residues, where the buried residues may act as essential scaffolding residues that maintain the structural integrity of the antigen binding site (Vajdos et al, page 423). Thus, Vajdos demonstrates that identification of key residues in an antibody that affect antigen binding and are not tolerant of modification, or which may only tolerate certain modifications, is a labor intensive process which cannot be predicted a priori. Chen et al. provides the results of random point mutation mutagenesis of the heavy chain CDR2 in the PC-specific T15 antibody and demonstrates that mutations in this CDR alone can abrogate binding and further that increasing the number of mutations within this one CDR results in a significant increase in non-binding mutants, from approximately 7% nonbinding mutants with 1 mutation to 58% nonbinding mutants with 2 mutations in HCDR2 (Chen et al., pages 855-859, Table 2).Chen et al. also demonstrated that mutations in at least 5 residues in this CDR2 were important in antigen binding (Chen et al., page 855). Thus, Chen et al., like Vajdos et al. demonstrates that mutations affecting antigen binding in antibody chains cannot be determined a priori, and further teaches that increasing the number of mutations within a CDR substantially increases the chances of generating a non-binding mutant. Sela-Culang et al., in a recent review of the structural basis of antibody-antigen recognition teaches that some off-CDR residues can contribute critically to the interaction of the antibody with antigen (Sela-Culang et al. (2013) Frontiers in Immunology, Vol. 4, pages 1-13, page 1). Sela-Culang et al. teaches that in some antibodies framework residues contribute to the antigen binding site, and in other antibodies, the frame work residues affect the antigen binding site indirectly by shaping the antigen binding site (Sela-Culang et al., page 7). In fact, Sela-Culang et al. teaches that constructing an antibody using only the CDRs from an known antigen-specific antibody usually results in a significant drop or a complete loss of binding of the antibody to its antigen (Sela-Culang et al., page 7). Sela-Culang et al. further teaches that different CDR identification methods may often identify radically different stretches as “CDRs”, indicating that CDRs are not well defined and thus are not necessarily a good proxy for the binding site (Sela-Culang et al., page 8). Thus, Sela-Culang et al. provides additional evidence that the binding site and criticality of residues in even a known antibody with known heavy and light chain sequences cannot be predicted a priori, including mutations within the framework regions of the antibody. Therefore, the prior art at time of filing clearly teaches that the structure and sequence of the binding region of an antibody specific for a particular peptide cannot be predicted by the observation of antigen binding and instead requires isolation of the antibody and experimentation determination of at minimum the heavy and light chain variable regions.
While one of ordinary skill in the art could use standard protocols to isolate and sequence an antibodies from the immunized mice disclosed in the working examples, to satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. Further, possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features if there any. See University of Rochester, 358 F.3d at 927, 69USPQ2d at 1895. Applicant must instead convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. As discussed in detail above, antibodies have no shared or common sequences or structures responsible for binding to a specific antigen. As stated in Eli Lilly, “Without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement”. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
An adequate written description for an antibody with specific functional properties of binding to a specific antigen, and further therapeutic effectiveness, requires more than a mere statement that it is part of the invention; what is required is a description of the chemical structures and physical properties of the antibody/antibodies itself. It is not sufficient to define the antibody solely by its principal biological property of binding to a peptide because disclosure of no more than that, as in the instant case, is simply a wish to know the identity of any antibody with that biological property. Also, naming a type of material generically known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material. Rather, it is an attempt to preempt the future before it has arrived. (See Fiers v. Revel, 25 USPQ2d 1601 (CA FC 1993) and Regents of the Univ. Calif. v. Eli Lilly & Co., 43 USPQ2d 1398 (CA FC, 1997)).
In view of these considerations, a skilled artisan would not have viewed the teachings of the specification as sufficient to show that the applicant was in possession of the claimed invention because it does not provide adequate written description for the broad genus of antibodies claimed having the recited functional ability to bind to an Aspergillus kexin and further exhibit therapeutic activity in vivo in a subject.
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Claims 26-35, 37, 52, and 54-70 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.
Claims 26-35, 37, and 54-70 are drawn to methods of preventing or treating aspergillus infection, aspergillosis, or conditions associated with aspergillus infection either in an immunosuppressed or non-immunosuppressed patient by administering an antiserum produced against an Aspergillus Kexin peptide, or an isolated and purified antibody produced against an Aspergillus Kexin peptide. The claim also include a product claim, claim 52, drawn to an isolated antiserum. Antiserum is defined in the specification refers to a blood serum that contains one or more antibodies, i.e. polyclonal antibodies, directed against a specific antigen, in this case an Aspergillus Kexin peptide. An “isolated or purified antibody” as defined by the specification encompasses monoclonal antibodies and fragments thereof including scFv, and humanized or human antibodies.
Given the broadest reasonable interpretation, the claims embrace an extremely large genus of polyclonal and monoclonal antibodies and their derivatives solely defined by their function- binding to an Aspergillus Kexin peptide. Note as well that with the exception of claim 37, which recites a specific Aspergillus fumigatus Kexin peptide with the amino acid sequence of SEQ ID NO:2 or SEQ ID NO:3, which only differ by 2 flanking amino acids, the claims read broadly on antiserum and antibodies that recognize and bind to a large genus of Aspergillus Kexin peptides, including full length Kexin polypeptides and peptides of any length derived from Kexin polypeptides from any species of Aspergillus, of which there are several hundred. Claims 31 and 66 limits the species of Aspergillus to 6 specific species, and claims 32 and 67 limit the species to Aspergillus fumigatus. Thus, the claims as a whole encompass potentially millions of different antibodies whose only shared feature is binding to one of several hundred different Aspergillus kexin polypeptides, or one of thousands of Aspergillus kexin peptides derived therefrom.
The specification fails to provide an adequate disclosure for the genus of antiserum or antibodies, and in particular monoclonal or polyclonal antibodies or fragments thereof, that are capable of binding to any Aspergillus kexin peptide, including the Aspergillus fumigatus peptides set forth as SEQ ID NOS: 2 and 3. The specification fails to provide sufficient guidance for the broad genus of antibodies encompassed by the claims in terms of distinguishing characteristics of the genus and in particular the structure properties of an antibody that define binding to any Aspergillus kexin peptide, such as heavy or light chain sequences, and in particular heavy and light chains CDR sequences, and further fails to provides sufficient description for antibodies that bind to Aspergillus kexin peptide and are capable of exhibiting a therapeutic effect on any species of Aspergillus infection or aspergillosis in a subject. The specification broadly discloses that anti-kexin antiserum can be generated by administering an Aspergillus kexin peptide to a subject. The specification also refers to the general knowledge in the art for standard procedures for obtaining antibodies including monoclonal antibodies, such as isolation of antibodies directly from the blood or the use of hybridomas. However, despite teaching that standard procedures are available to obtain antibodies and monoclonal antibodies, the specification does not actually describe any antibody which is capable of binding to any Aspergillus kexin peptide from any species of Aspergillus, and which further exhibits the functional property of having a therapeutic effect on Aspergillus infection or Aspergillosis in a subject.
Turning to the working examples, in example 5, the specification teaches that a recombinant AF.KEX1 peptide with the sequence of SEQ ID NO:2 was used to immunize immunocompetent mice, and that plasma obtained from the mouse post-immunization contained antibodies which recognized the AF.KEX1 peptide in vitro. However, the working examples do provide any structural or sequence information regarding any of the antibodies which may be present in the plasma and which are capable of binding to the peptide of SEQ ID NO:2. Further, the working examples do not provide any functional information for any single antibody or combination of antibodies present in the polyclonal serum in regards to binding characteristics, such as binding affinity to SEQ ID NO:3, or the specificity of the binding of any antibody to SEQ ID NO:3 versus other peptides, including potential cross-reactivity with other Aspergillus fumigatus kexin peptides, or other species of Aspergillus kexins. It is also noted that the working examples do not include any examples of the administration of any antiserum or antibody to any subject. While the working examples do test whether a mouse, immunocompetent or immunocompromised, when administered SEQ ID NO:2, protects from or reduces the effects of Aspergillus fumigatus infection, the working examples do actually use the plasma of the mouse to attempt to treat a mouse which has not received the AF.KEX1 peptide. Further, while the working examples do show that the AF.KEX1 peptide generated antibodies in the mouse, and the mice which have received the AF.KEX1 peptide (SEQ ID NO:2) exhibited a reduced fungal burden and development of aspergillosis following post-immunization challenge with Aspergillus fumigatus, the working examples do not attempt to correlate the beneficial effects on fungal burden with the activity of antibodies generated in the mice versus the activity of other parts of the immune system which are activated by kexin peptide immunization. Thus, as whole, the specification, including the working examples, fails to provide sufficient guidance for any antibody in terms of physical characteristics such as sequence or structure which is capable of binding any Aspergillus kexin peptide, or demonstrate that any single antibody or polyclonal antiserum which binds to any Aspergillus kexin peptide if capable of having a therapeutic effect in vivo on Aspergillus infection or associated conditions in a subject.
At the time of filing, the prior art teaches that antibody binding specificity for a particular antigenic peptide cannot be defined by common structure. Combinatorial diversity and somatic mutation during B cell development and maturation into antibody secreting cells contribute to the diversity of antibodies which are capable of recognizing a particular antigen epitope such that it is unlikely that any two antibodies which recognize the same antigen, or even antigen epitope would share the same amino acid or nucleic acid sequence. At the time of filing, the art teaches that antibody specificity and binding to antigen epitopes is largely determined by unique complementarity determining regions (CDRs). There are 6 CDRs produced by the pairing of heavy and light chain variable regions in an intact antibody. While the heavy chain CDR3 region has been implicated as being crucial for defining antigen specificity of an antibody, the art teaches that both CDRs and framework regions (FRs) in the heavy and light chain also contribute to and affect antigen specificity and affinity. The prior art at the time of filing does not teach any specific antibody binding motif or domain shared among all antibodies which bind to a specific antigen, nor does the prior art at the time of filing teach that specific residues at specific positions in the antibody heavy chain or light chain are either essential or non-essential to the binding of any and all antibodies. Instead, the prior art at the time of filing is replete with teachings that while the overall structure between antibodies is shared, the structure of the antigen binding region of an antibody and the residues involved in binding to its cognate antigen are unique to each antibody and can involve residues both within any one or all of the heavy and light chain CDRs and framework regions (see for example, Vajdos et al. (2002) J. Mol. Biol., Vol. 320, 415-428, Chen et al. (1992) J. Exp. Med., Vol. 176, 855-866, and Sela-Culang et al. (2013) Frontiers in Immunology, Vol. 4, pages 1-13). Vajdos et al. teaches that residues in both the CDRs and framework regions of antibodies can be important for antigen recognition and binding, and discloses attempts to identify key residues in the antigen binding site of the Fab2C4 antibody for its peptide epitope derived from the extracellular domain of the human oncogene ErbB2 (Vajdos et al., pages 416-418). Vajdos et al. teaches that two different mutagenesis strategies were used to identify key residues in peptide binding- shotgun alanine scanning mutagenesis and shotgun homolog-scanning mutagenesis- and report that the results of the two methods in combination three-dimensional crystal structure of the Fab2C4 antibody provided distinct yet complementary view of key residues in binding between the antibody and antigen (Vajdos et al., page 417, Figure 1 and Table 2). As can be seen in Figure 1, each method identified different key residues, with some overlap. Vajdos et al. states that key residues for binding are present in both the heavy and light chain and include both solvent exposed and buried residues, where the buried residues may act as essential scaffolding residues that maintain the structural integrity of the antigen binding site (Vajdos et al, page 423). Thus, Vajdos demonstrates that identification of key residues in an antibody that affect antigen binding and are not tolerant of modification, or which may only tolerate certain modifications, is a labor intensive process which cannot be predicted a priori. Chen et al. provides the results of random point mutation mutagenesis of the heavy chain CDR2 in the PC-specific T15 antibody and demonstrates that mutations in this CDR alone can abrogate binding and further that increasing the number of mutations within this one CDR results in a significant increase in non-binding mutants, from approximately 7% nonbinding mutants with 1 mutation to 58% nonbinding mutants with 2 mutations in HCDR2 (Chen et al., pages 855-859, Table 2).Chen et al. also demonstrated that mutations in at least 5 residues in this CDR2 were important in antigen binding (Chen et al., page 855). Thus, Chen et al., like Vajdos et al. demonstrates that mutations affecting antigen binding in antibody chains cannot be determined a priori, and further teaches that increasing the number of mutations within a CDR substantially increases the chances of generating a non-binding mutant. Sela-Culang et al., in a recent review of the structural basis of antibody-antigen recognition teaches that some off-CDR residues can contribute critically to the interaction of the antibody with antigen (Sela-Culang et al. (2013) Frontiers in Immunology, Vol. 4, pages 1-13, page 1). Sela-Culang et al. teaches that in some antibodies framework residues contribute to the antigen binding site, and in other antibodies, the frame work residues affect the antigen binding site indirectly by shaping the antigen binding site (Sela-Culang et al., page 7). In fact, Sela-Culang et al. teaches that constructing an antibody using only the CDRs from an known antigen-specific antibody usually results in a significant drop or a complete loss of binding of the antibody to its antigen (Sela-Culang et al., page 7). Sela-Culang et al. further teaches that different CDR identification methods may often identify radically different stretches as “CDRs”, indicating that CDRs are not well defined and thus are not necessarily a good proxy for the binding site (Sela-Culang et al., page 8). Thus, Sela-Culang et al. provides additional evidence that the binding site and criticality of residues in even a known antibody with known heavy and light chain sequences cannot be predicted a priori, including mutations within the framework regions of the antibody. Therefore, the prior art at time of filing clearly teaches that the structure and sequence of the binding region of an antibody specific for a particular peptide cannot be predicted by the observation of antigen binding and instead requires isolation of the antibody and experimentation determination of at minimum the heavy and light chain variable regions.
Turning to the use of any monoclonal antibody or polyclonal antibody serum for preventing or treating any Aspergillus infection or condition in an immunocompetent or immunocompromised patient, it is noted that the art at the time of filing teaches that the passive administration of antiserum or monoclonal antibodies for treatment of fungal disease was neither routine nor predictable. Elluru et al., for example, teaches that while some studies have determined that antibodies may have a role in restricting fungal burden and clearance during fungal infection, it is evident from the data on monoclonal antibodies that the efficacy of antibodies in fungal infections is dependent on epitope specificity, abundance of protective antibodies, and their isotype (Elluru et al. (2015) Semin. Immunopathol., Vol. 37: 187-197, see page 187). Elluru et al. teaches that there are many components of the immune system that act to protect from fungal infection and inhibit fungal growth, particularly the innate immune response and the phagocytic activity of macrophages and dendritic cells (Elluru et al., page 188). Elluru et al. teaches that initial studies to understand the role of antibodies in anti-fungal immunity were largely inconclusive due potentially to an insufficient proportion of protective antibodies in the serum that are capable of clearing fungal infection, and/or the presence of inhibitory antibodies in serum that neutralize the effect of protective antibodies (Elluru et al., page 188). More specifically in regards to treatment of Aspergillus infection and Aspergillus fumigatus in particular, Lian et al. teaches that in a recent review of advances in Aspergillus therapy that while monoclonal antibodies may have the potential to form the basis for novel treatments of aspergillus infection and Invasive aspergillosis (IA), they have yet to reach their full potential as of 2022 (Lian et al. (2022) Int. J. Mol. Sci., Vol. 23:5563, pages 1-16, see page 2). Lian et al. teaches that monoclonal antibodies against a number of cell wall antigens of Aspergillus fumigatus have been isolated and tested for antifungal activity in vitro and vivo, and provides review of the literature from the prior art and more recent studies, concluding that while there is evidence that passive immunization with monoclonal antibodies can act in preventing aspergillus infection and improve survival in mouse models of IA, there are no reports, even post-filing, of humanized or human monoclonal antibodies for use I prophylaxis or treatment of aspergillus infection or aspergillosis. Note as well that kexin is not a cell wall antigen of Aspergillus fumigatus. Thus, the prior art of record and statements made post-filing by the skilled artisan demonstrate that neither passive administration of antiserum comprising anti-fungal antibodies nor monoclonal antibodies specific for fungal antigen was considered routine or predictable as a means for preventing or treating aspergillus infection or aspergillosis at the time of filing.
Therefore, in view of the art recognized unpredictability in treating aspergillus infection or aspergillosis by passive administration of antiserum or a monoclonal antibody that binds to a fungal antigen, the complete lack of guidance for even a single antibody which recognizes any Aspergillus kexin peptide, the lack of working examples demonstrating the effects of the administration of any antiserum or monoclonal antibody that binds to any Aspergillus kexin peptide to inhibit or treat any species of Aspergillus infection, and the breadth of the claims, it would have required undue experimentation to make and use the anti-kexin antiserum and antibodies as claimed.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 26-35, 37, 52, and 54-70 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO 2019/067592 (April 4, 2019), hereafter referred to as Norris and Rabacal, with an effective filing date of 9/27/2017.
The applied reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Norris and Rabacal teach methods of treating or preventing infection and/or disease associated with a fungal pathogen such as Aspergillus in a subject in need, using an isolated antiserum, and antibody generated against an immunogenic peptide of a fungal pathogen, and in particular where the antiserum or antibody is against a Kexin peptide derived from Aspergillus (Norris and Rabacal, pages 2-3, 16, and 80-82). Norris and Rabacal disclose that the Aspergillus Kexin peptide recognized by the antiserum or antibody is an Aspergillus fumigatus Kexin peptide, and more specifically a 90 amino acid kexin peptide with a sequence identical to instant SEQ ID NO:2 (Norris and Rabacal, pages 3-4, see also Figure 3 and SEQ ID NO:10). Norris and Rabacal further teach that treating or preventing disease associated with aspergillus including preventing or treating aspergillosis, allergic pulmonary reactions, and lung infections (Norris and Rabacal, page 4). Norris and Rabacal further teach to administer the antiserum of antibody to a subject pre- or post-transplant, where the patient is immunosuppressed, and/or has received immunosuppressive drugs (Norris and Rabacal, page 85). Thus, by teaching all the limitations of the claims as written, Norris and Rabacal anticipate the instant claims as written.
Claims 26-35, 37, 52, and 54-70 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by U.S. Patent Application Publication 2020/0222517 (July 16, 2020), hereafter referred to as Norris et al., with an effective filing date of 9/27/2017.
The applied reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Norris et al. teach methods of treating or preventing infection and/or disease associated with a fungal pathogen such as Aspergillus in a subject in need, using an isolated antiserum, and antibody generated against an immunogenic peptide of a fungal pathogen, and in particular where the antiserum or antibody is against a Kexin peptide derived from Aspergillus (Norris et al., abstract, pages 1-2, 7, and 43-44). Norris et al. disclose that the Aspergillus Kexin peptide recognized by the antiserum or antibody is an Aspergillus fumigatus Kexin peptide, and more specifically a 90 amino acid kexin peptide with a sequence identical to instant SEQ ID NO:2 (Norris et al., page 2, see also Figure 3 and SEQ ID NO:10). Norris et al. further teach that treating or preventing disease associated with aspergillus including preventing or treating aspergillosis, allergic pulmonary reactions, and lung infections (Norris et al., page 1). Norris et al. further teach to administer the antiserum of antibody to a subject pre- or post-transplant, where the patient is immunosuppressed, and/or has received immunosuppressive drugs (Norris et al., pages 7 and 43-44). Thus, by teaching all the limitations of the claims as written, Norris et al. anticipate the instant claims as written.
Additional Comments
Note that WO 2019/067592 (April 4, 2019), hereafter referred to as Norris and Rabacal, has not been applied as prior art under 35 U.S.C. 102(a)(1) because as set forth in MPEP 2153.01(a), a disclosure made within the grace period is not prior art under AIA 35 U.S.C. 102(a)(1) if it is apparent from the disclosure itself that it is an inventor-originated disclosure. MPEP section 2153.01(a) explain that, “Office personnel may not apply a disclosure as prior art under AIA 35 U.S.C. 102(a)(1) if the disclosure: (1) was made one year or less before the effective filing date of the claimed invention; (2) names the inventor or a joint inventor as an author or an inventor; and (3) does not name additional persons as authors on a printed publication or joint inventors on a patent. This means that in circumstances where an application names additional persons as joint inventors relative to the persons named as authors in the publication (e.g., the application names as joint inventors A, B, and C, and the publication names as authors A and B), and the publication is one year or less before the effective filing date, it is apparent that the disclosure is a grace period inventor disclosure, and the publication is not prior art under AIA 35 U.S.C. 102(a)(1)”. This is the exact situation with WO 2019/067592, where the prior art document names as inventors Norris and Rabacal, and the instant application names as inventors Norris, Rabacal, and Rayens.
Further note that an obviousness type double patenting rejection based on the claims issued in U.S. Patent 11,547,747, hereafter referred to as the ‘747 patent, or claims issued in U.S. Patent 12,453,761, hereafter referred to as the ‘761 patent, has not been made as neither the claims in the ‘747 patent nor the claims in the ‘761 patent are directed to the same subject matter as currently claimed, but are rather directed to the subject matter of non-elected invention I.
No claims are allowed.
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Dr. A.M.S. Wehbé
/ANNE MARIE S WEHBE/Primary Examiner, Art Unit 1634