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 1-2, 12-17, 20-22, 37 and 39, and the species of clone S24-1476 for the first antibody/antigen binding fragment and clone S144-1339 as the second antibody/antigen binding fragment in the reply filed on 13 April 2026 is acknowledged.
Applicant asserts that claims 1, 2, 12-17, 20-22, 37 and 39 are “generic” or read on the elected species. While the claims do read on the elected species, the claims are not considered generic as the claims recite a Markush group (referring back to Table 1 of the specification) rather than a generic invention or generic antibody/antigen binding fragment.
Claims 25, 28-29, 31, 35, 51 and 59 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 13 April 2026.
Claims 1-2, 12-17, 20-22, 37 and 39 are under consideration in the instant Office action.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Drawings
The drawings are objected to for the following reasons:
Figure 1A-1E includes panels which reference the subparts in lower case letters which is not compliant with 37 CFR 1.84(u)(1). All of the figures which include subparts or additional panels fail to comply with 37 CFR 1.84(u)(1) as they all fail to utilize capital letters. Once the Figures are corrected, the Brief Description of the Drawings and the rest of the specification should be amended to reflect this correction.
Several Figures/panels are blurry (see for example Figure 1A, 1B, 1C, 1D, etc. which results in figure legends being unreadable, the axis labels being unreadable, details of the figures being undiscernible, etc. The drawings do not comply with 37 CFR 1.84(a)(1), (l) and (p) with regard to clarity, legibility, and solid, well-defined lines. See example below.
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Figure 1A appears to include nucleic acid sequences which do not include the required Sequence identifier (see screenshot below). Correction is required.
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Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Nucleotide and/or Amino Acid Sequence Disclosures
Applicant’s preliminary amendment filed 30 December 2025 to correct sequence deficiencies in the instant application (inclusion of Sequence identifiers and to update the incorporation statement) has been received and entered.
As noted above in the objection to the drawings, it would appear that Figure 1A includes nucleic acid sequences. These nucleic acid sequences do not include a reference to a Sequence identifier. Portions of Figure 1A are so blurry, it is not clear if a nucleic acid sequence is being depicted or not (portions of figure which have depiction of “Spike”, “NP”, “ORF8” and one other element which cannot be decerned). If there are nucleic acid sequence present, they must also have a Sequence identifier which could either be included in the drawing itself or in the Brief Description of the Drawings (with associated text to make clear which identifiers go to which sequence). If the sequences are not already included in the sequence listing which has been provided to the USPTO, a corrected sequence listing which includes the missing sequences will need to be provided. If a new listing is necessary, the incorporation statement will need to be corrected which will require a corrected substitute specification. If the identifiers are added to the specification, a corrected substitute specification will also be required.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because it refers to “the disclosure” as well as characterizing the invention as “novel”. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
The disclosure is objected to because of the following informalities: the text of the specification (version filed 30 December 2025) at pages 291-298 in the Tables does not comply with 37 CFR 1.52 (a)(1)(iv) as the text is not “plainly and legibly written”. The lines of the tables and the lines that create the text are blurry and not solid.
The use of various trade names and/or marks used in commerce has been noted in this application. See for example paragraph [0398] which recites EZ-Link™, and No-Weigh™. While this example does indicate that the appropriate symbol was used in this instance, the generic terminology is not found. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms. The entire specification should be reviewed for appropriate usage and inclusion of generic terminology.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is required.
Claim Objections
Claims 1-2 are objected to because of the following informalities: claims 1-2 refer to “a clone of Table 1”. MPEP 2173.05(s) indicates that the claims must be complete in themselves and incorporation by reference to a specific figure or table “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.” Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted). Reference to the table and incorporation of the subject matter which is being claimed would be remedial.
Claim 1 is objected to for the following grammatical error: the recitation of “a antibody clone” in line 4 should be “an antibody clone”.
Appropriate correction is required.
Improper Markush
Claims 1-2 (and dependent claims 12-17, 20-22, 37 and 39) are rejected on the 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). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Antibodies which bind to leptin are not a recognized physical or chemical class. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of clones/heavy/light chain variable regions/CDRs in claims 1-2 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: the different collections of heavy chain/light chains and CDRs relate to a multitude of specific antibodies which bind a specific target and not necessarily the same target. The structures of these heavy/light chains and CDRs are not shared by the different alternatives because each antibody has a specific amino acid sequence and therefore, the recited species do not share a common structure which provides for a common function and therefore, are not proper species of one another.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
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 1-2, 12-16, 20-21, 37 and 39 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 antigen binding fragment comprising a heavy/light chain variable region comprising 6 CDRs having at least 80% sequence identity to SEQ ID NO:561-563 and 570-572 (elected species of antibody; clone S24-1476). Example 1, beginning at page 251 of the specification (filed 13 April 2026), states that peripheral blood mononuclear cells (PBMCs) and serum was collected from 25 subjects upon recovery from SARS-CoV-2 viral infection from which B cells were identified which were specific to SARS-CoV-2 spike protein, spike RBD, ORF7a, ORF8 and NP. CD19+ B cells were then used to prepare probes and libraries. B cells specific to SARS-CoV-2 viral proteins were identified and 90 monoclonal antibodies were synthesized and characterized (see [0389]). The amino acid sequence information for specific clones is provided in Table 1 (pages 90-168). Therefore, the antibody of the instant claims is a natural product produced by a B cell obtained from a human subject following recovery from SARS-CoV-2 viral infection. The B cells and the antibodies they produce, are natural products. Therefore, an antibody characterized by these CDR structures as recited in the instant claims is a natural product.
This judicial exception is not integrated into a practical application because the claims are to the antibody or antigen binding fragment and there are no additional limitations that would integrate the exception into a practical application. Claims 12-13 recite certain characteristics of the antibody of claim 1. Claim 14 recites that the antibody/antigen binding fragment is one of a number of different antibody formats, including a human antibody. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no additional elements recited in the claims.
Claim 15 is directed to an antigen binding fragment with a particular format. However, the claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the antigen binding fragment is a nature-based product which does not differ from the naturally-occurring structure found in the intact antibody. Claim 16 is directed to a polypeptide comprising the antigen binding fragment of claim 1, which read on the intact antibody which is a natural product. Claim 20 is directed to a composition comprising the antibody or antigen binding fragment of claim 1 and claim 21 recites that the composition comprises a pharmaceutical excipient however, the inclusion of the antibody/antigen binding fragment in a composition with or without an excipient does not sufficient to amount to significantly more than the judicial exception as the excipient does not significantly alter the structure or the function of the antibody/antigen binding fragment. Furthermore, the composition could be plasma or blood which would further be a natural product and not distinguish the antibody/antigen binding fragment from what would be found in nature.
Claim 37 is directed to a method for treating or preventing a coronavirus infection in a subject by administering the antibody/antigen binding fragment of claim 1 and claim 39 limits the coronavirus infection to SARS-CoV-2. However, the antibody/antigen binding fragment was obtained from a B cell of a patient who was recovering from a SARS-CoV-2 infection. Therefore, the instant claim encompasses a natural process as the subject was infected with SARS-CoV-2, the subjects immune system generated B cells which produced antibodies which were “administered” and the antibodies bound to antigens of the SARS-CoV-2, thus “treating” the infection. Therefore, the claims encompass a natural process which uses the natural product of the instant claims and therefore, does not add significantly more to the judicial exception.
Applicant’s attention is directed to the USPTO January 7, 2019 Revised Patent Subject Matter Eligibility Guidance (i.e. Guidance) available at URL: https://www.govinfo.gov/content/pkg/FR-2019-01-07/pdf/2018-28282.pdf.
The guidance addresses the impact of Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S._, 133 S. Ct. 2107, 2116, 106 USPQ2d 1972 (2013) (Myriad) on the Supreme Court’s long-standing “rule against patents on naturally occurring things”, as expressed in its earlier precedent including Diamond v. Chakrabarty, 447 U.S. 303 (1980) (Chakrabarty), and Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. _, 132 S. Ct. 1289, 101 USPQ2d 1961 (2012) {Mayo). See Myriad, 133 S. Ct. at 2116. Myriad relied on Chakrabarty as “central” to the eligibility inquiry, and re-affirmed the Office’s reliance on Chakrabartys criterion for eligibility of natural products (i.e., whether the claimed product is a non-naturally occurring product of human ingenuity that is markedly different from naturally occurring products). Id. at 2116-17. Myriad also clarified that not every change to a product will result in a marked difference, and that the mere recitation of particular words (e.g., “isolated”) in the claims does not automatically confer eligibility. Id. at 2119. See also Mayo, 132 S. Ct. at 1294 (eligibility does not “depend simply on the draftsman’s art”). Thus, while the holding in Myriad was limited to nucleic acids, Myriad is a reminder that claims reciting or involving natural products should be examined for a marked difference under Chakrabarty.
In Mayo Collaborative Services v. Prometheus Laboratories, Inc. (Mayo) 101
USPQ2d 1961, 1965-1966 (SC 2012) it was stated:
“Phenomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U. S. 63, 67 (1972). And monopolization of those tools through the grant of a patent might tend to impede innovation more than it would tend to promote it. (Emphasis added)
Still, as the Court has also made clear, to transform an unpatentable law of nature into a patent-eligible application of such a law, one must do more than simply state the law of nature while adding the words “apply it.”
Our conclusion rests upon an examination of the particular claims before us in light of the Court’s precedents. Those cases warn us against interpreting patent statutes in ways that make patent eligibility “depend simply on the draftsman’s art” without reference to the “principles underlying the prohibition against patents for [natural laws].” Flook, supra, at 593. They warn us against upholding patents that claim processes that too broadly preempt the use of a natural law. Morse, supra, at 112- 120; Benson, supra, at 71-72. And they insist that a process that focuses upon the use of a natural law also contain other elements or a combination of elements, sometimes referred to as an “inventive concept,” sufficient to ensure that the patent in practice amounts to significantly more than a patent upon the natural law itself. Flook, supra, at 594; see also Bilski, supra, at_(slip op., at 14) (“[T]he prohibition against patenting abstract ideas ‘cannot be circumvented by attempting to limit the use of the formula to a particular technological environment’ or adding ‘insignificant post solution activity’” (quoting Diehr, supra, at 191-192)). (Emphasis added)
We find that the process claims at issue here do not satisfy these conditions, in particular, the steps in the claimed processes (apart from the natural laws themselves) involve well-understood, routine, conventional activity previously engaged in by researchers in the field. At the same time, upholding the patents would risk disproportionately tying up the use of the underlying natural laws, inhibiting their use in the making of further discoveries. (Emphasis added)
For the reasons set forth above, when the claims are considered as a whole, the claims are not considered to recite something significantly more than a judicial exception and thereby are not directed to patent eligible subject matter.
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 1-2, 12-17, 20-22, 37 and 39 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 are directed to an antibody or antigen binding fragment (no indication of what antigen is bound by the fragment) comprising CDRs, wherein the CDRs have at least 80% sequence identity to a given sequence (claim 1) and wherein the heavy and light chain variable regions come from Table 1. The elected species for examination is indicated to be clone S24-1476 (found at page 108 of the specification filed 13 April 2026). Claim 17 requires two antigen binding fragments, wherein each is independently selected from an antigen binding fragment of claim 1; the second election of species is indicated to be clone S144-1339 (found at page 105 of the specification filed 13 April 2026).
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Example 1, beginning at page 251 of the specification (filed 13 April 2026), states that peripheral blood mononuclear cells (PBMCs) and serum was collected from 25 subjects upon recovery from SARS-CoV-2 viral infection from which B cells were identified which were specific to SARS-CoV-2 spike protein, spike RBD, ORF7a, ORF8 and NP. CD19+ B cells were then used to prepare probes and libraries. B cells specific to SARS-CoV-2 viral proteins were identified and 90 monoclonal antibodies were synthesized and characterized (see [0389]). The amino acid sequence information for specific clones is provided in Table 1 (pages 90-168). While the specification provides structures for a large number of antibodies, the specification provides no information as to modifications to the CDR regions of these antibodies.
The specification fails to provide an adequate written description an antibody or antigen binding fragment comprising a heavy chain variable region and a light chain variable region wherein the heavy chain variable region comprises a HCDR1, HCDR2, and HCDR3 having at least 80% sequence identity to the HCDR1, HCR2, HCR3 from a heavy chain variable region of an antibody clone of Table 1 and wherein the light chain variable region comprises a LCDR1, LCDR2, and LCDR3 having at least 80% sequence identity to the LCDR1, LCDR2, and LCDR3 from the light chain variable region of the same antibody clone of Table 1. The instant specification does not provide an adequate written description for CDRs of a given antibody differing by up to 20% from the nature amino acid sequence for the given antibody as currently claimed.
The elected invention (clone S24-1476) in the instant application is an antibody which has 6 CDRS which have the amino acid sequences of SEQ ID NO:561-563 and 570-572 (heavy and light chain CDRs 1-3, respectively). The elected invention also has heavy/light chain variable regions with the amino acid sequence of SEQ ID NO:560 and 569 as well as heavy/light chains with the amino acid sequence of SEQ ID NO:559 and 568. For claim 17 which recites two antigen binding fragments, the second elected species (clone S144-1339) has 6 CDRs (SEQ ID NO: 471-472 and 480-482) as well as heavy/light variable regions (SEQ ID NO: 470 and 479) and heavy/light chains (SEQ ID NO: 469 and 478). These molecules have written description.
The prior art recognizes that the 6CDRs of an antibody are the portion of the antibody that primarily define the binding region of a given antibody. However, the instant specification does not adequately describe antibodies or antigen binding proteins that differ by as much as 20% from the native amino acid sequence of the disclosed antibody/antigen binding fragment. The specification further fails to provide any structure/function relationship for the recited CDRs and any possible mutation/alteration that would encompass up to 20% variation in the disclosed structures. It does not appear that the instant disclosure modified any of the isolated antibodies.
The structures of the antigen binding proteins claimed are not adequately described. In AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc., Ill USPQ2d 1780 (Fed. Cir. 2014) AbbVie had claims to functionally claimed antibodies and Centocor presented evidence that the antibodies described in AbbVie's patents were not representative of other members of the functionally claimed genus. The decision states, “When a patent claims a genus using functional language to define a desired result, ‘the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus.’ Id. at 1349. We have held that 'a sufficient description of a genus ... requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can “visualize or recognize” the members of the genus.’ Id. at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). Here, the claimed invention is a class of fully human antibodies that are defined by their high affinity and neutralizing activity to human IL-12, a known antigen. AbbVie's expert conceded that the '128 and '485 patents do not disclose structural features common to the members of the claimed genus.”
The AbbVie decision considers how large of a genus is involved and what species of the genus are described in the patent. With the written description of a genus, however, merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus. See Ariad, 598 F.3d at 1353 (The written description requirement guards against claims that “merely recite a description of the problem to be solved while claiming all solutions to it and ... cover any compound later actually invented and determined to fall within the claim's functional boundaries.”).
The specification provides no written description for CDR structures which differ from those which are disclosed as encompassed by the claim limitation of “having at least 80% sequence identity”. There is no written description for any antibody/antigen binding fragment with as much as 20% variation in amino acid sequence structure, as encompassed by the claims, nor have any functional antibodies which bind to particular target with such variation been described. Furthermore, claim 1 does not even recite what the antigen-binding fragment binds. There is no written description for making the multitude of encompassed CDRs recited with an expectation of obtaining an antibody or antigen binding fragment that has any particular functional activity.
In the instant application, the specification and claims draw a fence around a perceived genus but the genus is not adequately described. While the specification discloses an antibody clone S24-1476 which comprises CDRs with the amino acid sequences of SEQ ID NO:561-563 and 570-572 which binds spike protein and RBD, the claims are not so limited and the structural variability of the claimed genus is large as it encompasses numerous variations in the CDRs without any recitation of binding and/or functionality. No reasonable structure-function correlation has been established that is commensurate in scope with the claims and the specification does not describe representative examples to support the full scope of the claims as not a single variant of a given antibody has been provided.
The state of the prior art is such that the formation of an intact antigen-binding
site of antibodies routinely 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). 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. (PNAS 79: 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. MacCallum et al. (J. Mol. Biol. 262: 732-745, 1996) analyzed many different antibodies for interactions with antigen and state that although CDR3 of the heavy and light chain dominate, a number of residues outside the standard CDR definitions make antigen contacts (see page 733, right column) and non-contacting residues within the CDRs coincide with residues as important in defining canonical backbone conformations (see page 735, left column). De Pascalis et al. (J. Immunol. 169: 3076-3084, 2002) demonstrate that grafting the CDRs into a human framework was performed by grafting CDR residues and maintaining framework residues that were deemed essential for preserving the structural integrity of the antigen binding site (see page 3079, right column). Although abbreviated CDR residues were used in the constructs, some residues in all 6 CDRs were used for the constructs (see page 3080, left column). Thus, the art discloses that a change of even one amino acid of an antibody may change the ability of that antibody to bind to its original epitope. In addition, the art discloses that amino acids outside the CDRs are critical for antigen binding.
The fact that not just one CDR is essential for antigen binding or maintaining the conformation of the antigen binding site is underscored by Casset et al. (Biochem. Biophys. Res. Comm. 307: 198-205, 2003) which constructed a peptide mimetic of an anti-CD4 monoclonal antibody binding site by rational design and the peptide was designed with 27 residues formed by residues from 5 CDRs (see entire document). Casset et al. also states that although CDR H3 is at the center of most if not all antigen interactions, clearly other CDRs play an important role in the recognition process (page 199, left column) and this is demonstrated in this work by using all CDRs except L32 and additionally using a framework residue located just before the H3 (see page 202, left column). Chen et al. (J. Mol. Biol. 293: 865-881, 1999) describe high affinity variant antibodies binding to VEGF wherein the results show that the antigen binding site is almost entirely composed of residues from heavy chain CDRs, CDRH1-H3 (page 866). Wu et al. (J. Mol. Biol. 294: 151-162, 1999) state that it is difficult to predict which framework residues serve a critical role in maintaining affinity and specificity due in part to the large conformational change in antibodies that accompany antigen binding (page 152, left column) but certain residues have been identified as important for maintaining conformation.
In the absence of sufficient direction and guidance, the disclosure of a specific antibody/antigen-binding fragment which comprises CDRs of SEQ ID NO:561-563 and 570-572 does not provide sufficient written description for the entire genus of antigen binding proteins which lack such sequences as encompassed by the claims in view of the evidence cited above.
Vas-Cath Inc. V. Mahurkar, 19 USPQ2d 1111, states that Applicant must 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. The invention, for purposes of the written description inquiry, is whatever is now claimed (see page 1117). To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus. Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). In Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. At section B(1), the court states, “An adequate written description of a DNA ... requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention.”
Thus, given the level of skill and knowledge and predictability in the art, those of skill in the art would not conclude that the applicant was in possession of the claimed genera of antibody variants based on disclosures set forth above. "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." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004). For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly.
Further, it is not sufficient to define the genus solely by its principal biological property, because an alleged conception having no more specificity than that is simply a wish to know the identity of any material with that biological property. Per the Enzo court's example, (Enzo Biochem, Inc. v. Gen-Probe Inc., 63 USPQ2d 1609 (CA FC 2002) at 1616) of a description of an anti-inflammatory steroid, i.e., a steroid (a generic structural term) couched "in terms of its function of lessening inflammation of tissues" which, the court stated, "fails to distinguish any steroid from others having the same activity or function" and the expression "an antibiotic penicillin" fails to distinguish a particular penicillin molecule from others possessing the same activity and which therefore, fails to satisfy the written description requirement. Applicant has not disclosed any relevant, identifying characteristics, such as structure or other physical and/or chemical properties, sufficient to show possession of the claimed genus. Mere idea or function is insufficient for written description; isolation and characterization at a minimum are required. A description of what a material does, rather than what it is, usually does not suffice. (Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406).
In the absence of sufficient recitation of distinguishing characteristics, the specification does not provide adequate written description of the claimed genus, which are antigen binding proteins which vary from the disclosed antibody which comprises SEQ ID NO561-563 and 570-572. One of skill in the art would not recognize from the disclosure that the applicant was in possession of the genus. The specification does not clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed (see Vas-Cath at page 1116).
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).
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 1-2, 12-17, 20-22, 37 and 39 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.
Claims 1-2, 12-17, 20 and 37 are indefinite because the claim recites “antigen-binding fragment” but the claim does not indicate what is being bound. Without knowing what is bound, it is unclear what would constitute an “antigen-binding fragment”. Antibodies can bind many different things even if the antibody was generated against a single antigen, therefore, the metes and bounds of “antigen-binding fragment” is indefinite. Claims 21-22 and 39 are indefinite for depending on an indefinite claim.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 12-14 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 12-13 appear to fail to further limit the subject matter of the claim from which they depend. A given antibody/antigen binding fragment has characteristics such as equilibrium dissociation constant and ability to neutralize the antigen to which it binds. Claims 12-13 appear to merely recite properties/characteristics which are already possessed by the antibody/antigen-binding fragment of claim 1 and therefore those characteristics/properties are inherent and claims 12-13 do not further limit the subject matter of claim 1.
Claim 14 attempts to limit the antibody/antigen binding fragment of claim 1 to humanized antibody, chimeric antibody, antibody derivative, veneered antibody and single domain antibody. The antibody/antigen binding fragment of claim 1 was obtained from a human B-cell, therefore, the antibodies/antigen binding fragments are human in nature. A humanized antibody would not include all the limitations of the claim from which it depends because a humanized antibody would comprise CDRs from a different species with select positions being changed to amino acids that would reduce the incidence of inappropriate immune responses, therefore, it does not include all the limitations of the claim from which it depends. A chimeric antibody is one that combines the antigen-binding region (variable domains) of a non-human animal with the functional regions (constant domains of a human antibody), which again would mean that this embodiment would not include all the limitations of the claim from which it depends. Antibody derivative is not defined but may encompass embodiments which do not include all the limitations of the claim from which it depends (such as additional modifications in the CDR regions). A veneered antibody is a type of engineered antibody which normally replaces exposed, foreign-looking surface amino acids of a non-human antibody with human-like ones. Because the antibody/antigen binding fragment of claim 1 is human in origin, a veneered antibody would not include all the limitations of the claim from which it depends. A single domain antibody is comprised of only heavy chain regions and therefore, would not include all the limitations of the claim from which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Conclusion
No claim is allowed.
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/Christine J Saoud/Primary Examiner, Art Unit 1645
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