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 .
Claims 1-21 are pending.
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 02/08/2026 is acknowledged. The following species elections are acknowledged:
HCDR1 (SEQ ID NO:4), HCDR2 (SEQ ID NO:25), HCDR3 (SEQ ID NO:46)
LCDR1 (SEQ ID:172), LCDR2 (SEQ ID NO:193), LCDR3 (SEQ ID NO:214)
VH of SEQ ID NO:353 and VL of SEQ ID NO:354
SIF-001 as the specific antibody by laboratory designation.
Claims 3-6, 12-13, 16-17, and 19-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-2, 7-11, 14-15, 18, and 21 are pending and under consideration.
Information Disclosure Statement
Some of the information in the IDS filed 10/29/2025 could not be considered. For example, CN115427449 and CN117561080 did not appear to be present in the file although the corresponding WO documents were present. Under the non-patent literature documents, the line item for the international search report could not be considered because it lacked a date. Further, the abstract of the Rasool et al. document could not be considered due to the poor quality of the scan.
Also, the listing of references in the specification (last page) 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.
Specification
The disclosure is objected to on page 45, [0127], because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
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, 7-8, 10-11, 14-15, 18, and 21 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. This is a Written Description rejection.
The claims are broadly drawn antibodies or binding fragments thereof that bind to Galectin-3. Claims 1-2 define the antibodies by the complementary determining regions (CDRs) wherein the heavy (HCDRs 1-3) and light (LCDRs) chain CDRs have at least 70% identity to applicant’s elected species (see para 2 above). Further, regarding claims 1, 7, and 11 the claims include the phrase “and/or”. For example, claim 1 is drawn to a HCDR1 amino acid sequence at least 70% identical to any one of SEQ ID NOS: 1-21 and 370-389, a HCDR2 amino acid sequence at least 70% identical to any one of SEQ ID NOS: 22-42 and 390-417, and/or a HCDR3 amino acid sequence at least 70% identical to any one of SEQ ID NOS: 43-63 and 418-439, and/or a light chain variable (VL) region comprising. The use of “and/or” introduces alternative antibody structures such as those that do not require all of six CDRs or even the three CDRs of the light chain. Claim 7 presents the same option in that both variable light chains and variable heavy chains are written in the alternative. Dependent claims 7-8 are inclusive of at least 70% identity to a corresponding variable heavy (SEQ ID:353) and variable light (SEQ ID:354) region. Claims 10 is drawn to the antibodies of claim 1 and include humanized, chimeric, and human antibody forms. Claims 11 is inclusive of fusion polypeptides that comprise a variable heavy and/or variable light chain of Claim 1. Claim 18 is broadly drawn to claim 1 but wherein each CDR can have up to three substitutions, optionally at specific residues. However, what applicants are in possession of is an anti-Galactin-3 antibody comprising HCDR1 (SEQ ID NO:4), HCDR2 (SEQ ID NO:25), HCDR3 (SEQ ID NO:46) and LCDR1 (SEQ ID:172), LCDR2 (SEQ ID NO:193), LCDR3 (SEQ ID NO:214) or an antibody comprising the VH domain of SEQ ID NO:353 and the VL domain of SEQ ID NO:354. Claim 21 was included in this rejection because the broadest reasonable interpretation of “comprising a sequence of” can be any two peptides of each CDR and is thus not limited each CDR defined by uppercase amino acids. Thus, the claims are broadly drawn to a genus of antibodies that bind to galactin-3 defined by percent identity (70%) to the six CDRs.
A description of a genus of may be achieved by means of a recitation of a representative number of species, defined by structure, falling within the scope of the genus. However, the instant specification fails to provide sufficient descriptive information, such as definitive structural or functional features of the claimed genus of antibodies that bind to galactin-3 defined by a genus of amino acids within the CDR regions. Since the disclosure fails to describe the common attributes or characteristics that identify members of the genus, and because the genus is highly variant, the disclosure of one such species of CDRs is insufficient to describe the large diverse genus of antibodies that are capable of binding to galactin-3. Thus, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe and enable the genus as broadly claimed.
It is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin.
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. Chiu et al. (Antibodies 2019 8(4);55, 1-80) taught the antigen binding of antibodies often results in conformational changes in the contact surface areas of both the antibody and the antigen (page 5, first paragraph). Thus, the prediction of CDR binding to the epitope is difficult to predict. Chiu further taught antibody modeling has been shown to be accurate for the framework region sequences, but CDR modeling requires further development and improvements (page 6, second paragraph). Prediction of the structure of HCDR3 could not be accurately produced when given the Fv structures without their CDR-H3s (page 6, second paragraph). Chiu taught the quality of antibody structure prediction, particularly regarding CDR-H3, remains inadequate, and the results of antibody–antigen docking are also disappointing (page 11, paragraph 2). 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. (Biochemical and Biophysical Research Communications, Vol. 307, pg. 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 (Abstract). 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 col.) and this is demonstrated in this work by using all CDRs except L2 and additionally using a framework residue located just before the H3 (see page 202, left col.). Vajdos et al. (Journal of Molecular Biology, Vol. 320, pg. 415-428, 2002) additionally state that antigen binding is primarily mediated by the CDRs and that the more highly conserved framework segments which connect the CDRs are mainly involved in supporting the CDR loop conformations although in some cases framework residues also contact the antigen (page 416, left col.). Thus, 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. Thus, the art demonstrates that the antibody structure correlated with its antigen-binding function is six defined CDRs, and the position of each CDR.
Moreover, all of the claims can have as much as 30% variability in the CDR regions or in the entire VH or VL regions and applicants are not in possession of the genus of variant CDRs or VH/VL domains. However, the instant specification fails to provide sufficient descriptive information, such as definitive structural or functional features of the claimed genus of CDRs or variable domains that defines anti-galactin 3 binding requirements. Since the disclosure fails to describe the common attributes or characteristics that identify members of the genus, and because the genus is highly variant, the disclosure of 70% variability to a genus of anti-galactin 3 antibodies is insufficient to describe the large genus. In this case, a recitation of “percent identity” does not necessarily limit the differences in amino acid sequence to residues outside the CDRs. And while it is possible to screen for variants that retain antigen binding, it is respectfully submitted that the number of possible substitutions permitted by “percent identity” language does not allow the skilled artisan to envisage those variants not yet made which would retain the required function. The heavy chain variable region section alone recited in the instant claim 8 (SEQ ID NO:353) is over 100 amino acids. If one amino acid is substituted by each of the other 19 amino acids in a polypeptide with only 100 residues, there are 1,900 variant polypeptides. Substituting 30 amino acids (i.e., 30% identity) results in approximately 190030 variant polypeptides, or over 2.398 variants for a single variable region. The ability of the claimed antibody to bind to its antigen is an essential feature of the claimed invention; therefore, the skilled artisan would need to identify functional variants of the antibody in order to make and use the invention. The diversity of polypeptide libraries that can be screened by present-day high-throughput methods is generally assumed to be about 109, or one billion variants. E.g., Rentero et al., Chimia, 65: 843-845 (2011); see entire document, in particular e.g. the first sentence of the Introduction at page 843). Thus, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe and enable the genus as broadly claimed.
Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991) clearly states “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 page 1117.) 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). As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of second polypeptides, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required.
Thus, only an antibody claiming the six defined CDRs of HCDR1 (SEQ ID NO:4), HCDR2 (SEQ ID NO:25), HCDR3 (SEQ ID NO:46) and LCDR1 (SEQ ID:172), LCDR2 (SEQ ID NO:193), LCDR3 (SEQ ID NO:214) or an antibody comprising the VH domain of SEQ ID NO:353 and the VL domain of SEQ ID NO:354 but not the full scope of the claims meets the written description.
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 and 18 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, 7-8, 9-11, 14-15, 18, 21 are rejected under the judicially approved ''improper Markush grouping'' doctrine. (See Federal Register, Vol. 76, No. 27, Wednesday, February 9, 2011, page 7166). A Markush claim may be rejected under judicially approved "improper Markush grouping" principles when the claim contains an improper grouping of alternatively useable members. A Markush claim contains an "improper Markush grouping" if either: (1) the members of the Markush group do not share a "single structural similarity" or (2) the members do not share a common use. Supplementary Guidelines at 7166 (citing In re Harnisch, 631 F.2d 716, 721-22, 206 USPQ 300, 305 (CCPA 1980)) This rejection is appropriate when the claim contains an improper grouping of alternatively useable species. Where a Markush grouping describes part of a chemical compound, regardless of whether the claim is limited to a compound per se or the compound is recited as part of a combination or process, the members following "selected from the group consisting of" (or similar introductory phrase) need not share a community of properties themselves; the propriety of the grouping is determined by a consideration of the compound as a whole. See Harnisch, 631 F.2d at 722, 206 USPQ at 305 ("in determining the propriety of a Markush grouping the compounds must be considered as wholes and not broken down into elements or other components"). See also In re Jones, 162 F.2d 479, 481, 74 USPQ 149, 151 (CCPA 1947) ("In determining the propriety of a Markush grouping, moreover, the compounds which are grouped must each be considered as a whole and should not be broken down into elements or other components").
Thus, the Markush grouping of the anti-galactin 3 antibodies is improper because the compounds must be considered as a whole and the alternatives (e.g., defined by up to 30% variability and including various substitutions) would encompass thousands of diverse antibody structures with or without the properties of binding to galactin-3. Thus, the multitude of alternatives would not share both a single structural similarity and a common use. 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. MPEP 2117.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GARY B NICKOL, Ph.D. whose telephone number is (571)272-0835. The examiner can normally be reached M-F 9AM-5:30PM.
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/GARY B NICKOL/Primary Examiner, Art Unit 1643