DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 51-53 and 65, and the required species: MxR-B11 antibody (which the specification indicates has a CDRH1 of SEQ ID NO: 43, CDRH2 of SEQ ID NO: 44, CDRH3 of SEQ ID NO: 45, CDRL1 of SEQ ID NO: 46, CDRL2 “DNN”, CDRL3 of SEQ ID NO: 47, VH of SEQ ID NO: 178, and VL of SEQ ID NO: 179, in the reply filed on 4/23/2026 is acknowledged.
Claims 54-64 and 66-70 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 4/23/2026.
Claims 51-53 and 65 are under examination on the merits.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) submitted on 3/2/2026, 4/28/2025, 1/14/2025, and 9/22/2023 are in compliance with 37 CFR 1.97. Accordingly, the references in the IDSs are being considered by the examiner.
Claim Objections
Claim 51 is objected to because of the following informalities: claim 51 contains a typographical mistake on line 2, where “a complementarity determining regions” should instead recite “a complementarity determining region”; claim 51 should also recite the target of the antibody in line 1 of the claim. Appropriate correction is required.
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.
Scope of Enablement
Claims 51-53 and 65 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 monoclonal antibody wherein the antibody comprises a complete set of six CDRs that can bind its target, does not reasonably provide enablement for antibody molecules containing an incomplete set of CDRs. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
The breadth of the claims is found in claim 51.
The nature of the invention is “an antibody or binding fragment thereof, comprising: a complementarity determining region (CDR) heavy (H)1 comprising SEQ ID NO: 43, a CDRH2 comprising SEQ ID NO: 44, a CDRH3 comprising SEQ ID NO: 45, a CDR light (L)1 comprising SEQ ID NO: 46, a CDRL2 comprising DNN, and a CDRL3 comprising SEQ ID NO: 47”. As discussed in the rejection under 35 U.S.C. §112(b) below, it is unclear whether the claim is drawn to (i) a single molecule comprising the 6 recited CDRs or a solution with identical antibodies comprising the CDRs, or (ii) the claimed CDRs are present on different antibodies within the same solution (e.g., a polyclonal antibody). Thus, the claimed antibodies read on a polyclonal antibody, wherein each clone can possess less than the full claimed set of CDRs. However, to be properly enabled, the claimed antibody must be defined by its 6 CDRs on a single molecule. Claim 52 also recites antibodies that comprise a heavy chain variable domain as set forth in SEQ ID NO: 178 or a sequence with at least 95% sequence identity to SEQ ID NO: 178, and a light chain variable domain as set forth in SEQ ID NO: 179 or a sequence with at least 95% sequence identity to SEQ ID NO: 179. Claim 52 also reads on a polyclonal antibody composition, wherein no single antibody necessarily contains all 6 claimed CDRs or both variable chains.
The level of skill of one skilled in this art is high.
The specification teaches a number of antibodies that bind to HMPV/RSV prefusion protein, and defines their 6 CDRs (CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3, and variable domains). See e.g., paras. [0017] and [0073]. These teachings do not enable the full breadth of the claims because an antibody lacking any of the 6 parental CDRs would not predictably bind antigen.
The state of the prior art is such that it is well established in the art that the formation of an intact antigen-binding site of antibodies generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs or hypervariable regions, which provide the majority of the contact residues for the binding of the antibody to its target epitope (Paul, Fundamental Immunology, 3rd Edition, 1993, pp. 292-295, under the heading “Fv Structure and Diversity in Three Dimensions”). The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity, which is characteristic of the immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites (Paul, page 293, first column, lines 3-8 and line 31 to column 2, line 9 and lines 27-30).
Additionally, Bendig M. M. (Methods: A Companion to Methods in Enzymology, 1995; 8:83-93) reviews that the general strategy for “humanizing” antibodies involves the substitution of all six CDRs from a rodent antibody that binds an antigen of interest, and that all six CDRs are involved in antigen binding (see entire document, but especially Figures 1-3). It is noted that Bendig used Kabat CDRs in their humanization process (Pg. 86, Column 2, Paragraph, second). Similarly, the skilled artisan recognized a “chimeric” antibody to be an antibody in which both the heavy chain variable region (which comprises the three heavy chain CDRs) and the light chain variable region (which comprises the three light chain CDRs) of a rodent antibody are recombined with constant region sequences from a human antibody of a desired isotype (see entire document, but especially Figures 1-3).
Thus, the state of the art recognized that it would be highly unpredictable that a specific antibody binding domain comprising less than all six parental CDRs would have antigen binding function. The minimal structure which the skilled artisan would consider predictive of the function of binding the antigen of an antibody includes six CDRs (three from the heavy chain variable region and three from the light chain variable region) in the context of framework sequences which maintain their correct spatial orientation and have the requisite binding function. One of skill in the art would neither expect nor predict the appropriate functioning of the antibodies as broadly as currently claimed.
In view of the lack of the predictability of the art to which the invention pertains as evidenced by Paul and Bendig, the lack of guidance and direction provided by applicants, and the absence of working examples, undue experimentation would be required to make and use functional antibodies with binding domains having fewer than all six CDRs with a reasonable expectation of success, absent a specific and detailed description in applicant’s specification of how to effectively practice this and absent working examples providing evidence which is reasonably predictive that the claimed antibodies are functional, commensurate in scope with the claimed invention.
In the case of antibodies, it is especially important to disclose which residues are permissive to mutation. Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al. (Proceedings of the National Academy of Sciences USA, Vol., 79, Pg. 1979-1983, 1982). Rudikoff et al. teach that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function (Abstract).
Not knowing, absent further experimentation, which modifications function and which do not, when, as set forth above, even a single change of an encoded amino acid can unpredictably affect antibody structure and function, leads to one having no predictability or expectation of success for the function of any given antibody modification. Such random experimentation to identify at a later time what structure or fragment or modification is or is not functional and is embraced by Applicant’s claims is undue experimentation. This affects all claims that can mutate any CDR by reciting percent identity, for example claim 52.
Moreover, claims not containing elements critical or essential to the practice of the invention, such as antibodies or antibody fragments not having all of the relevant functional complementarity determining regions (CDRs) in the proper site on an appropriate antibody heavy or light chain framework, are not enabled by the disclosure. See In re Mayhew, 527 F.2d 1229, 188 USPQ 356 (CCPA 1976).
Note that an enabling disclosure for the preparation and use of only a few analogs of a product does not enable all possible analogs where the characteristics of the analogs are unpredictable. See Amgen Inc. v. Chugai Pharmaceutical Co. Ltd. (18 USPQ 2d 1027 (CAFC 1991)).
It is recommended that monoclonal be added before antibody in claim 51.
Written Description
Claims 51-53 and 65 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.
The instant claims above are drawn to a genus of antibodies or binding fragments thereof, comprising particular CDRs. However, each antibody generally requires at least 6 CDRs to function, yet the claims encompass a polyclonal antibody, wherein the particular claimed CDRs may be present on different antibody clones of the polyclonal antibody composition. See rejection under 35 U.S.C. §112(b) below. Thus, there are embodiments of the claimed invention that are not defined by a total set of 6 CDRs for each antibody molecule therein. Similarly, claim 52 also recites antibodies that comprise a heavy chain variable domain as set forth in SEQ ID NO: 178 or a sequence with at least 95% sequence identity to SEQ ID NO: 178, and a light chain variable domain as set forth in SEQ ID NO: 179 or a sequence with at least 95% sequence identity to SEQ ID NO: 179. Claim 52 also reads on a polyclonal antibody composition, wherein no single antibody necessarily contains all 6 claimed CDRs or both variable chains .
When one goes to the instant specification to identify a representative number of species to define the claimed genera with respect to such an antibody, they do not find any representative species of an antibody able to bind its target with less than a full set of 6 CDRs specific for the particular epitope.
Even if the prior art is aware of such antibodies, the totality of known antibodies would not be representative of each entire genus for the reasons discussed below. Claims 52-53 and 65 depend on claim 51 but do not remedy this deficiency, and therefore also fail the written description requirement.
On 22 February 2018, the USPTO provided a Memorandum clarifying the Written Description Guidelines for claims drawn to antibodies. That Memorandum indicates that, in compliance with recent legal decisions, the disclosure of a fully characterized antigen no longer is sufficient written description of an antibody to that antigen. Accordingly, the instant claims have been evaluated in view of that guidance.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the 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. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
An applicant may show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613.
Furthermore, to satisfy the written description requirement for the genus antibody capable of binding to its target epitope with incompletely defined CDRs, Applicant must adequately describe representative antibodies to reflect the structural diversity of the claimed genus. See Eli Lilly, 119 F.3d at 1568 (“[N]aming 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.”); Fiers v. Revel, 984 F.2d 1164, 1171 (Fed. Cir. 1993) (“Claiming all DNA[s] that achieve a result without defining what means will do so is not in compliance with the description requirement; it is an attempt to preempt the future before it has arrived.”).
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A “representative number of species” means that the species which are adequately described are representative of the entire genus. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 111 USPQ2d 1780 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, as here in which the antibodies claimed can have incomplete CDR sets, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615. “A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.” One of skill in this art cannot envision the structure of any antibody comprising less than 6 CDRs that alone specifically binds to its target epitope. Therefore, since no species is provided to represent these genera, the claims encompassing the same clearly fail the written description requirement.
Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. See ABBVIE DEUTSCHLAND GMBH & 2 CO. v. JANSSEN BIOTECH, INC., Appeals from the United States District Court for the District of Massachusetts in Nos. 09-CV-11340-FDS, 10-CV-40003-FDS, and 10-CV-40004-FDS, Judge F. Dennis Saylor, IV. See also Ariad, 598 F.3d at 1351 (“[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology.”); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011) (noting the technical challenges in developing fully human antibodies of a known human protein).
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members. The Federal Circuit has cautioned that, for claims reciting a genus of antibodies with particular functional properties (e.g., high affinity, neutralization activity, competing with a reference antibody for binding), “[c]laiming antibodies with specific properties, e.g., an antibody that binds to human TNF-α with A2 specificity, can result in a claim that does not meet written description even if the human TNF-α protein is disclosed because antibodies with those properties have not been adequately described." Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011).
“Functional” terminology may be used “when the art has established a correlation between structure and function” but “merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing one has invented a genus and not just a species.” Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 598 F3d 1336, 94 USPQ2d 1161, 1171 (Fed Cir. 2010). Since the CDR set of each antibody is responsible for antigen binding function of an antibody, and said set varies structurally from antibody to antibody, there is no correlation between structure and function between the members of an antibody genus. One cannot “represent” the entire genus defined only by function with any structural consensus. Thus, functional language should not be used to define an antibody genus. Rather, structure should be used.
Even when several species are disclosed, these are not necessarily representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, as here, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. Since each genus recited in the instant claims is large, it would be very challenging to describe sufficient species to cover the structures of the entire genus. Zero species is certainly not adequate.
Overall, at the time the invention was made, the level of skill for preparing antibodies and then selecting those antibodies with desired functional properties was high. However, even if a selection procedure was, at the time of the invention, sufficient to enable the skilled artisan to identify antibodies with the recited functional properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336 (Fed. Cir. 2010); see also Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1876 (Fed. Cir. 2011) (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”) Absent the conserved structure provided by all six CDRs of a parental antibody in the context of appropriate VH and VL framework sequences, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, what an antibody with a particular set of functional properties would look like structurally.
Since no antibodies possessing less than 6 CDRs are shown to be capable of binding to a target epitope, the instant claims above clearly fail the written description requirement. A representative number of species has not been taught to describe these genera. Given the well-known high level of polymorphism of immunoglobulins / antibodies, the skilled artisan would not have been in possession of the vast repertoire of antibodies and the unlimited number of antibodies encompassed by the claimed invention; one of skill in the art would conclude that applicant was not in possession of the structural attributes of a representative number of species possessed by the members of the genera of antibodies capable of binding its target epitope that only comprise less than 6 CDRs, partial CDRs, or heavy chain variable domains or light chain variable domains having at least 95% sequence identity. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genera.
Owed to the variation among antibodies with respect to their CDRs, the structure of antibodies that correlates with their function, it is very difficult to provide adequate representation of a functionally defined antibody genus. There is unlikely to be any CDR structure shared by the entire genus, for example. Also, the disclosure of one set of antibody CDRs does not guide one of skill to the next set of CDRs. This is because it is well-known in this art that mutation of CDR residues leads to loss of antigen binding. Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al. (Proceedings of the National Academy of Sciences USA, Vol., 79, Pg. 1979-1983, 1982). Rudikoff et al. teach that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function (Abstract). Thus, while applicant has described one or a few species within each of the genera recited, and the art may provide more, each genus is very large and would encompass antibody structures (CDR sets) that cannot be visualized from the prior art or instant disclosure. One of skill in this art cannot determine the antibody structures encompassed by the claimed genera only defined by function. Any future antibody structure may or may not be encompassed, and if it is, it would not have been represented in Applicant’s disclosed species. Thus, the described species cannot be considered representative of the recited genera of antibodies. E.g., AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, the claims are rejected here.
As discussed above, an applicant may show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613. Therefore, it is recommended that the instant claims be amended to recite complete structural information of the claimed antibodies that bind their target epitopes, including full CDRs, specific, and full-length heavy and light variable chain domains.
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 51-53 and 65 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 51 recites “an antibody or binding fragment thereof, comprising: a complementarity determining region (CDR) heavy (H)1 comprising SEQ ID NO: 43, a CDRH2 comprising SEQ ID NO: 44, a CDRH3 comprising SEQ ID NO: 45, a CDR light (L)1 comprising SEQ ID NO: 46, a CDRL2 comprising DNN, and a CDRL3 comprising SEQ ID NO: 47”. However, it is unclear whether the claim is drawn to (i) a single molecule comprising the 6 recited CDRs or a solution with identical antibodies comprising the CDRs, or (ii) the claimed CDRs are present on different antibodies within the same solution (e.g., a polyclonal antibody). Claims 52-53 and 65 are also indefinite because they depend on claim 51 but do not resolve the lack of clarity. The examiner suggests adding “Monoclonal” at the beginning of claim 51 to resolve the lack of clarity and prevent the claims from reading on a polyclonal antibody composition.
Claim 53 is indefinite because it recites “an IgG antibody with M252Y, S254T, and T256E mutations in the Fc region”, but it is unclear which numbering scheme these residues refer to, as there are multiple Fc numbering schemes commonly used in the art, for example EU or Kabat. The claims are indefinite without a reference to a numbering scheme to determine which residues must be mutated.
Claim Rejections – Improper Markush Grouping
Claims 51-53 and 65 are rejected on the judicially-created basis that they contain an improper Markush grouping of alternatives.
See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984).
The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature. The members of the improper Markush grouping do not share a substantial structural feature and a common use that flows from the substantial structural feature for the following reasons:
MPEP 803.02 provides guidance on the analysis of a proper Markush group. Members of a proper Markush group are disclosed in the specification to possess at least one property in common which is mainly responsible for their function in the claimed relationship, and it is clear from their very nature or from the prior art that all of them possess this property. The MPEP further provides that in the members of a proper Markush group there should be (1) a common utility, and (2) a substantial structural feature essential to that utility.
In the instant case, claims 51-53 and 65 include the group of antibodies or binding fragments, but they do not appear to share a substantial structural feature. Claim 51 recites a number of antibodies or binding fragments defined by sequences that comprise their CDRs, and claim 52 recites a number of antibodies or binding fragments defined by VL and VH sequences. The six CDRs are the substantial structural feature responsible for antigen binding function. However, each of these sequences is unique. The state of the prior art is such that it is well established in the art that the formation of an intact antigen-binding site of antibodies generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs or hypervariable regions, which provide the majority of the contact residues for the binding of the antibody to its target epitope (Paul, Fundamental Immunology, 3rd Edition, 1993, pp. 292-295, under the heading “Fv Structure and Diversity in Three Dimensions”). Thus, a common use cannot flow from a shared substantial structural feature in these claims. Since the instant claims contain Markush groups with members of antibodies or binding fragments that possess differing sequences lacking shared, discernable, discrete domains associated with the claims; function of binding target epitopes, the claims contain an improper Markush group and are rejected here.
In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. §134 and 37 CFR 41.31(a)(1).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 51-53 and 65 are rejected under 35 U.S.C. 101 because
the claimed invention is directed to a natural product without significantly more. The claim(s) recite(s) “an antibody or binding fragment thereof, comprising: a complementarity determining region (CDR) heavy (H)1 comprising SEQ ID NO: 43, a CDRH2 comprising SEQ ID NO: 44, a CDRH3 comprising SEQ ID NO: 45, a CDR light (L)1 comprising SEQ ID NO: 46, a CDRL2 comprising DNN, and a CDRL3 comprising SEQ ID NO: 47”. The claimed antibodies are a judicial exception because they encompass natural products. This judicial exception is not integrated into a practical application because the claimed antibody appears to be a natural product isolated from human B cells without additional elements that raise it above well-understood, routine, and convention due to lack of such elements. The specification seems to indicate that the antibodies of the disclosure were generated from human subjects that possessed viral immunity from natural infection (spec., paras. [0195-198] “a pre-screen of donors for sero-positivity against HPIV3 was not needed”), so these antibodies were naturally produced in the human subject. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim does not recite additional elements.
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.
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Claims 51-53 and 65 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 47-54 of copending Application No. 19/108,083 (reference application, PGPub US 20250304657 A1) in view of Jung (Biotechnology and Bioprocess Engineering 18: 625-636. 2013). Although the claims at issue are not identical, they are not patentably distinct from each other because each set of claims is drawn to an antibody or binding fragment thereof comprising CDRH1 of SEQ ID NO: 43, CDRH2 of SEQ ID NO: 44, CDRH3 of SEQ ID NO: 45, CDRL1 of SEQ ID NO: 46, CDRL2 of “DNN” and CDRL3 of SEQ ID NO: 47 (instant claim 51, ‘083 claim 52). Each set of claims also encompasses an antibody comprising a variable chain comprising a sequence as set forth in SEQ ID NO: 178 or a sequence with at least 95% sequence identity to the sequence as set forth in SEQ ID NO: 178, and a variable light chain comprising a sequence as set forth in SEQ ID NO: 178 or a sequence with at least 95% sequence identity to the sequence as set forth in SEQ ID NO: 179 (instant claim 52, ‘083 claim 53). Each set of claims also encompasses embodiments of a composition comprising the claimed antibodies and a pharmaceutically-acceptable carrier (instant claim 65, ‘083 claim 54). Therefore, instant claims 51-52 and 65 are not patentably distinct from the copending claims.
The claims differ in that the instant claims are also drawn to an antibody or binding fragment thereof, whereas the copending claims are drawn specifically to an antibody. The claims also differ in that while the ‘083 claims require an antibody with a mutated Fc region including modifications M252Y, S254T, T256E, M428L, and N434S, the instant claim 53 encompasses an antibody with M25Y, S254T, and T256E mutations in the Fc region.
Notably, the instant claim 53 requires that the antibody is an IgG antibody, which the copending claims do not require.
Jung discloses that the antibody Fc region mediates potent immune effector functions by engaging Fc receptors and serum complement proteins (Abstract), and that IgG antibodies show highly specific targeting abilities and excellent serum half-lives compared to small-molecule chemical drugs (p. 625, col. 1). Jung also teaches that pH-dependent human FcRn (hFcRn) binding is critical for the serum half-life of a therapeutic antibody, and engineering Fc domains may improve pH-dependent hFcRn binding profiles (p. 631, col. 1, para. 3), and a triple mutation at the CH2-CH3 interface region (M252Y/S254T/T256E) exhibits approximately 10-fold improved ph-dependent hFcRn binding affinity at pH 6.0 and increased serum half-life by 4-fold in a cynomolgus monkey model (p. 631, col. 2, para. 3).
Therefore, it would have been obvious to one of ordinary skill in the art to make and use therapeutic antibodies that are IgG with M252Y/S254T/T256E mutations in the Fc domain. One of ordinary skill in the art would have been motivated to increase the serum-half life of the antibody. There would have been a reasonable expectation of success because these mutations are known and well-characterized in therapeutic antibodies. Therefore, claims 51-53 and 65 were prima facie obvious to one of ordinary skill in the art.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEFFREY MARK SIFFORD whose telephone number is 571-272-7289. The examiner can normally be reached 8:30 a.m. - 5:30 p.m. ET with alternating Fridays off.
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/JEFFREY MARK SIFFORD/Examiner, Art Unit 1671 /Michael Allen/Supervisory Patent Examiner, Art Unit 1671
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