The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
The amendment filed on 9-29-2025 is acknowledged. Claims 1, 6, 12-13 and 15-17 have been amended. Claims 3-5, 7-8, 14 and 19-25 have been canceled. Claims 1-2, 6, 9-13 and 16-18 are pending. Claim 18 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1-2, 6, 9-13 and 16-17 are currently under examination.
Sequence Compliance
The objection to the specification/drawings for no being in sequence compliance is maintained for reasons of record. Applicant’s argument that the multitude of sequences in Figure 1A are all SEQ ID NO:2 and those in Figure 1B are all SEQ ID NO:14 is noted. However, neither the specification nor the drawings reflect it. The only mention of Figure 1A and Figure B is on page 10 which states:
Figure 1 shows a complete analysis (ProPred predictions) of the antigenic regions within a SpCBM sequence (Figure 1A) and a PaTD sequence (Figure 1B). Predicted binders are coloured blue, with the first residue of each binding region shown in red. Predicted antigenic peptides (green bars) and ProImmune (purple bars) are shown under the sequences.
There is no mention of any SEQ ID NO:s much less SEQ ID NO:2 or SEQ ID NO:14. Moreover, it is unclear why if all the sequences in a given drawing are the same why each sequence has a different identifying label.
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - Sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.831(c). Sequence identifiers for sequences (i.e., “SEQ ID NO:X” or the like) must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Amended drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers (i.e., “SEQ ID NO:X” or the like) into the Brief Description of the Drawings, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Claim Objections Withdrawn
The objection to claims 1-3 and 4 for reciting claim language drawn to non-elected inventions is withdrawn in light of the amendment thereto.
Claim Rejections Withdrawn
The rejection of claims 1-9 under 35 U.S.C. 102(a)(1) as being anticipated by Taylor et al. (WO 2015/110831 – IDS filed on 9-6-2022) is withdrawn in light of the amendment thereto.
Claim Rejections Maintained
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.
The rejection of claims 1-2, 6, 9-13 and 16-17 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 is maintained for reason of record. Cancellation of claims 3-5, 7-8, 14 and 19-25 has rendered the rejection of those claims moot. 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.
Applicant argues:
1. Claim 1 has been amended to incorporate the limitations of claim 14 which was not part of the rejection.
Applicant’s arguments have been fully considered and deemed non-persuasive.
With regard to Point 1, the amendment is insufficient to overcome the rejection of record. The amended claims are now drawn to sialic acid binding molecules comprising one or more modified family 40 carbohydrate binding modules (CBM40s) wherein said CBM40s contain one or more mutations relative to a reference sequence “derived” from SEQ ID NO:1 and wherein said CBM40s have an A162P mutation. Given, the specification is silent with regard to what constitutes a “derived” CBM sequence, the instant claims still read any sialic acid binding molecules comprising a CBM40 which has a proline at the position correlating to position 162 of SEQ ID NO:1 as well as those sialic acid binding molecules comprising an oligomerization domain “derived” from the Pseudomonas aeruginosa pseudaminidase of SEQ ID NO:13.
To adequately describe the genus of molecules capable of binding sialic acid, Applicant must adequately describe the amino acids within a given CBM40 that is essential for said binding when part of a given fusion protein. This entails not only defining the sequence of the CBM40(s) but the sequence of the other portions of the sialic acid binding molecule as well. The specification, however, does not disclose distinguishing and identifying features of a representative number of members of the genus of antibodies to which the claims are drawn, such as a correlation between the structure of the sialic acid binding molecules and its recited function (e.g. binding sialic acid when part of a fusion protein; modulating IL-8 expression), so that the skilled artisan could immediately envision, or recognize at least a substantial number of members of the claimed genus of sialic acid binding molecules. Additionally, with regard to claims 6 and 16-17, Applicant must adequately describe what mutations can be made in the Pseudomonas aeruginosa pseudaminidase of SEQ ID NO:13 and still maintain its ability to oligomerize a given sialic acid binding molecule. Even in situations where there is some confidence of a similar overall structure between two proteins, only experimental research can confirm the artisan's best guess as to the function of the structurally related protein. Thus, one skilled in the art would not accept the assertion, which is based only upon an observed similarity in amino acid sequence, that a variant of a given polypeptide would necessarily have the same biological activities as the parent polypeptide. Accordingly, it follows that the variant molecules that can bind sialic acid can only be identified empirically. Therefore, absent a detailed and particular description of a representative number, or at least a substantial number of the members of the genus of modified CBM40s and oligomerization domains, the skilled artisan could not immediately recognize or distinguish members of the claimed genus of sialic acid binding molecules to which the claims refer.
The instant claims are drawn to sialic acid binding molecules comprising one or more modified family 40 carbohydrate binding modules (CBM40s) wherein said CBM40s contain one or more mutations relative to a reference sequence “derived” from SEQ ID NO:1 and wherein said CBM40s have an A162P mutation. Moreover, said sialic acid binding molecules can optionally:
contain an oligomerization domain “derived” from SEQA ID NO:13 and variants thereof (claim 6);
modulates IL-8 expression (claim 9); or
inhibits IL-8 in A549 cells (claims 10 and 11).
Given, the baseline sequence is of the CBM40 is variable (with the exception of CBM40s consisting of SEQ ID NO:1) and that the none of the portions of the sialic acid binding molecules are defined, none of the recited compositions meet the written description provision of 35 USC 112, first paragraph. The specification provides insufficient written description to support the genus encompassed by the claims.
To adequately describe the genus of molecules capable of binding sialic acid, Applicant must adequately describe the amino acids within a given CBM40 that is essential for said binding when part of a given fusion protein. This entails not only defining the sequence of the CBM40(s) but the sequence of the other portions of the sialic acid binding molecule as well. The specification, however, does not disclose distinguishing and identifying features of a representative number of members of the genus of antibodies to which the claims are drawn, such as a correlation between the structure of the sialic acid binding molecules and its recited function (e.g. binding sialic acid when part of a fusion protein; modulating IL-8 expression), so that the skilled artisan could immediately envision, or recognize at least a substantial number of members of the claimed genus of sialic acid binding molecules. Additionally, with regard to claims 6 and 16-17, Applicant must adequately describe what mutations can be made in the Pseudomonas aeruginosa pseudaminidase of SEQ ID NO:13 and still maintain its ability to oligomerize a given sialic acid binding molecule. Even in situations where there is some confidence of a similar overall structure between two proteins, only experimental research can confirm the artisan's best guess as to the function of the structurally related protein. Thus, one skilled in the art would not accept the assertion, which is based only upon an observed similarity in amino acid sequence, that a variant of a given polypeptide would necessarily have the same biological activities as the parent polypeptide. Accordingly, it follows that the variant molecules that can bind sialic acid can only be identified empirically. Therefore, absent a detailed and particular description of a representative number, or at least a substantial number of the members of the genus of modified CBM40s and oligomerization domains, the skilled artisan could not immediately recognize or distinguish members of the claimed genus of sialic acid binding molecules to which the claims refer.
MPEP § 2163.02 states, “[a]n objective standard for determining compliance with the written description requirement is, 'does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed' ”. The courts have decided:
The purpose of the “written description” requirement is broader than to merely explain how to “make and use”; the 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 is, for purposes of the “written description” inquiry, whatever is now claimed.
See Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991). Furthermore, the written description provision of 35 USC § 112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
MPEP 2163.02 further states, “[p]ossession may be shown in a variety of ways including description of an actual reduction to practice, or by showing the invention was 'ready for patenting' such as by disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention” See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997); Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it"). Moreover, because the claims encompass a genus of variant species, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed.
Additionally, MPEP 2163 states:
"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)”
And:
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, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date." See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014) (Holding that claims to all human antibodies that bind IL-12 with a particular binding affinity rate constant (i.e., koff) were not adequately supported by a specification describing only a single type of human antibody having the claimed features because the disclosed antibody was not representative of other types of antibodies in the claimed genus, as demonstrated by the fact that other disclosed antibodies had different types of heavy and light chains, and shared only a 50% sequence similarity in their variable regions with the disclosed antibodies.).
Given the lack of a specific baseline sequence either the unmodified sialic acid binding molecule generally or the CBM40 specifically or the specific mutations that can be made while maintaining the recited biological characteristics set forth in the specification between structure and function as required by the written description requirements.
Protein chemistry is probably one of the most unpredictable areas of biotechnology. Consequently, the effects of sequence dissimilarities upon protein structure and function cannot be predicted. Bowie et al (Science, 1990, 257:1306-1310) teach that an amino acid sequence encodes a message that determines the shape and function of a protein and that it is the ability of these proteins to fold into unique three-dimensional structures that allows them to function and carry out the instructions of the genome and further teaches that the problem of predicting protein structure from sequence data and in turn utilizing predicted structural determinations to ascertain functional aspects of the protein is extremely complex. (column 1, page 1306). Bowie et al further teach that while it is known that many amino acid substitutions are possible in any given protein, the position within the protein's sequence where such amino acid substitutions can be made with a reasonable expectation of maintaining function are limited. Certain positions in the sequence are critical to the three-dimensional structure/function relationship and these regions can tolerate only conservative substitutions or no substitutions (column 2, page 1306). The sensitivity of proteins to alterations of even a single amino acid in a sequence are exemplified by Burgess et al (J. of Cell Bio. 111:2129-2138, 1990) who teach that replacement of a single lysine reside at position 118 of acidic fibroblast growth factor by glutamic acid led to the substantial loss of heparin binding, receptor binding and biological activity of the protein and by Lazar et al. (Molecular and Cellular Biology, 1988, 8:1247-1252) who teach that in transforming growth factor alpha, replacement of aspartic acid at position 47 with alanine or asparagine did not affect biological activity while replacement with serine or glutamic acid sharply reduced the biological activity of the mitogen. These references demonstrate that even a single amino acid substitution will often dramatically affect the biological activity and characteristics of a protein. Protein function is context dependent, and both molecular and cellular aspects have to be considered (p. 398, column 2). Conclusions from the comparison analysis are often stretched with regard to protein products (p. 398, column 3). Further, although gene annotation via sequence database searches is already a routine job, even here the error rate is considerable (p. 399, column 2). Most features predicted with an accuracy of greater than 70% are of structural nature and, at best, only indirectly imply a certain functionality (see legend for table 1, page 399). As more sequences are added and as errors accumulate and propagate it becomes more difficult to infer correct function from the many possibilities revealed by database search (p. 399, paragraph bridging columns 2 and 3). The reference finally cautions that although the current methods seem to capture important features and explain general trends, 30% of those features are missing or predicted wrongly. This has to be kept in mind when processing the results further (p. 400, paragraph bridging cols 1 and 2). Clearly, given not only the teachings of Bowie et al., Lazar et al. and Burgess et al. but also the limitations and pitfalls of using computational sequence analysis and the unknown effects of alternative splicing, post translational modification and cellular context on protein function as taught by Bork, the functional variants of the polypeptide of SEQ ID NO:1 (and variants and fragments thereof) cannot be predicted. Clearly, it could not be predicted that a polypeptide that is a “variant” of a given reference sequence (e.g. SEQ ID NO:1) will function in a given manner. Reasonable correlation must exist between structure and function. In the instant case there is no correlation between the structure (i.e. sequence) of a given variant sialic acid binding molecule and its recited function (bind sialic acid). The specification, however, fails to disclose which amino acid residues of a given modified CBM40 are essential for the reciting biological functions or which amino acids might be added, replaced or deleted so that the resultant polypeptide retains the immunological characteristics of its parent, or by which other amino acids the essential amino acids might be replaced with so that the resultant peptide retains the biological characteristics of its parent.
Recently, describing molecules by their functions was addressed in the Centocor decision (CENTOCOR ORTHO BIOTECH, INC. v ABBOTT LABORATORIES (Fed Cir, 2010-1144, 2/23/2011)). In said case the court stated”
To satisfy the written description requirement, "the 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,' and demonstrate that by disclosure in the specification of the patent." Carnegie Mellon Univ. v. Hoffmann-La Roche Inc., 541 F.3d 1115, 1122 (Fed. Cir. 2008) (quoting Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563-64 (Fed. Cir. 1991)). Assessing such "possession as shown in the disclosure" requires "an objective inquiry into the four corners of the specification." Ariad, 598 F.3d at 1351. Ultimately, "the specification must describe an invention understandable to [a person of ordinary skill in the art] and show that the inventor actually invented the invention claimed." Id. A "mere wish or plan" for obtaining the claimed invention is not adequate written description. Regents of the Univ. of Cal. v. Eli Lilly & Co., 119 F.3d 1559, 1566 (Fed. Cir. 1997).
The court further opined that Centocor's suggestion
that our decision in Noelle and the PTO written description guidelines support the view that fully disclosing the human TNF-α protein provides adequate written description for any antibody that binds to human TNF-α. That suggestion is based on an unduly broad characterization of the guidelines and our precedent.
The court concluded that
While our precedent suggests that written description for certain antibody claims can be satisfied by disclosing a well-characterized antigen, that reasoning applies to disclosure of newly characterized antigens where creation of the claimed antibodies is routine. Claiming 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.
Given the skilled artisan would not be able to predict whether a given modified CBM40/ sialic acid binding molecules would be able to bind sialic acid when part of a fusion protein, there is no correlation between structure and function as required by the written description requirements. Consequently, proper written description is lacking.
New Grounds of Rejection
35 USC § 112
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, 6, 9-13 and 16-17 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 1 is rendered vague and indefinite by the use of the phrase “…wherein the modified CBM40 is derived from the CBM sequence of SEQ ID NO: 1 and relative to the CBM sequence of SEQ ID NO: 1 the modified CBM40 of the sialic acid binding molecule comprises a substitution of the alanine residue at position 162 with a proline residue.”. It is unclear whether the modified CBM40 “derived” from SEQ ID NO:1 must have the full sequence set forth in SEQ ID NO:1 or merely have a proline at the position that correlates to position 162 of SEQ ID NO:1. As written, it is impossible to determine the metes and bounds of the claimed invention.
Claim 6 is rendered vague and indefinite by the use of the phrase “…wherein the modified oligomerization domain is derived from the oligomerization domain of Pseudomonas aeruginosa pseudaminidase of SEQ ID NO: 13 and relative to SEQ ID NO: 13 contains one or more mutations. It is unclear what is meant to be engendered by said phrase as there is no requirement that the claimed oligomerization domain “derived” from SEQ ID NO:13 have any similarity to the sequence of SEQ ID NO:13. As written, it is impossible to determine the metes and bounds of the claimed invention.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
/ROBERT A ZEMAN/Primary Examiner, Art Unit 1645 January 29, 2026