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 .
Priority
The instant application, filed October 23, 2023, is a continuation of PCT application PCT/US2022/026005, filed April 22nd, 2022, which claims domestic benefit to US provisional application 63/179,879, filed on April 26th, 2021.
Status of Claims
The preliminary amendment filed February 5th, 2024 for claims filed on October 23rd, 2023 is acknowledged. Claims 1-2,5,7,9,11,13,15,18,22-23,26-27,29,35,37-39,42-43,45,48-49,52-54,62-64,68-69,72-73,76-77,88,102,104,108 and 110-111 are currently pending and are examined on the merits herein.
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.
Claim 37 is 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 the pharmaceutical antibody formulation comprising the HCDR1-3 and LCDR1-3 and corresponding SEQ ID NOs, does not reasonably provide enablement for the CDRs that can have up to 1, 2, 3, 4, or 5 amino acids changed from recited sequences. 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 and use the invention commensurate in scope with these claims.
Nature of the invention and breadth of claims
Claim 37 is drawn to pharmaceutical antibody formulation comprising: a therapeutically effective amount of an antibody, wherein the antibody comprises a HCDR1 having the sequence of SEQ ID NO: 2, a HCDR2 having the sequence of SEQ ID NO: 3, a HCDR3 having the sequence of SEQ ID NO: 4, a LCDR1 having the sequence of SEQ ID NO: 5, a LCDR2 having the sequence of SEQ ID NO: 6; and a LCDR3 having the sequence of SEQ ID NO: 7, wherein each CDR can have up to 1, 2, 3, 4, or 5 amino acids changed from the recited sequence. The invention as disclosed in claim 97 recite “wherein each CDR can have up to 1, 2, 3, 4, or 5 amino acids changed from the recited sequence. The claim encompasses a genus of heavy and/or light chain variable regions which are claimed as having the function of specifically binding to galectin 3 (instant disclosure, page 1, paragraph 0003). This means that the variability in the sequence identity can occur in the CDRs, which are domains that are critical for the antibody binding to its target. One of ordinary skill in the art would understand that the changes to the CDRs would result in unpredictable binding characteristics with no reasonable expectation of maintaining galectin 3 antigen binding. Additionally, the instant specification and claim 37 does not provide an adequate number of species of the claimed genus and does not provide a structure-function correlation that would allow for a person of ordinary skill in the art to envision what variation can occur to the CDR domains, such that the obtained structure would result in binding to galectin-3.
State of the prior art
At the time of filing, antibody functionality were known to depend on the entire structure, particularly a full complement of six CDRs. It is understood by one of ordinary skill in the art that a mutation of CDRs is unpredictable and requires structure-function testing as they would have different binding affinity and target specificity. Sela-Culang (Sela-Culang I, Kunik V, Ofran Y. The structural basis of antibody-antigen recognition. Front Immunol. 2013 Oct 8;4:302. doi: 10.3389/fimmu.2013.00302. PMID: 24115948; PMCID: PMC3792396.), reviews the structural basis of antibody-antigen recognition in the state of the art. Naturally occurring antibodies that have six hypervariable loops are commonly termed complementary determining regions (CDRs) and are widely assumed to be responsible for antigen recognition (page. 1, abstract; page. 3, “The Role of CDRs and their Definition”]. A person of ordinary skill in the art would understand that although the above basics of antibody-antigen binding are known, that the specifics of antibody structure (e.g., within the CDRs) that underlie the antigen recognition are not well characterized (page 1, “The Motivations for…”).
Further, Herold (Herold, E.M., John, C., Weber, B. et al. Determinants of the assembly and function of antibody variable domains. Sci Rep 7, 12276 (2017). https://doi.org/10.1038/s41598-017-12519-9) teaches that it should be emphasized that there is no correlation between experimentally determined change in antibody binding affinity and a given mutation and additionally that no such correlation is expected because antigen binding is “affected by each CDR loop differently” and changes thereto “can in principle affect antigen binding affinity in an unpredictable way” (page 14, paragraph 2). Further, Herold asserts that multiple determinants regulate antigen affinity and the interactions with CDRs are complex (page 14, paragraph 3).
At the time of filing, Stasenko teaches a species of an anti-galectin3 antibodies that could be used to treat ovarian cancer (Stasenko M, Smith E, Yeku O, Park KJ, Laster I, Lee K, Walderich S, Spriggs E, Rueda B, Weigelt B, Zamarin D, Rao TD, Spriggs DR. Targeting galectin-3 with a high-affinity antibody for inhibition of high-grade serous ovarian cancer and other MUC16/CA-125-expressing malignancies. Sci Rep. 2021 Feb 12;11(1):3718. doi: 10.1038/s41598-021-82686-3. PMID: 33580170; PMCID: PMC7881041, title). Stasenko teaches the “inhibitory murine monoclonal anti–Gal3 carbohydrate-binding domain antibody, 14D11” could be a “viable therapeutic strategy in patients with MUC16-expressing tumors, supporting further development of human blocking antibodies against Gal3 as potential cancer therapeutics” (page 1, abstract). Furthermore, Invitrogen teaches a list of multiple antibody clones that have different species specificity as well as different epitope binding and affinity (Anonymous “Anti-Galectin 3 Antibodies | Invitrogen.” Archive.org, 2019, web.archive.org/web/20191020134455/www.thermofisher.com/antibody/primary/target/galectin%203. Accessed 11 June 2026.). Therefore, the prior art demonstrates that there are multiple antibodies that bind to galectin-3 and does not teach the predictability of the CDR residues that would allow a person of ordinary skill in the art to make the antibody that would have a binding affinity to galectin-3.
Existence of working examples and amount of direction by the applicant
The claims and the instant disclosure does not provide an adequate number of species of the claimed genus of the antibody that would allow for a person of ordinary skill in the art to envision what variation can occur to the light and heavy chains, particularly in the CDR regions, such that the obtained structure would result in the antibody that can bind to galectin 3 (specification, page 1, paragraph 0003). Applicant recites only one species of the antibody TB006 and the CDRs sequences (Drawings, page 2, FIG. 2A). Applicant only shows working examples of the TB006 antibody to formulate in a pharmaceutical formulation and in the method to treat Alzheimers (page 119, Example 1).
Relative skill of those in the art, level of predictability, and quantity of experimentation needed to make or use the invention
Making changes to the CDR sequence of an antibody sequence is a highly unpredictable process and one skilled in the art, like a highly skilled scientist, could not a priori make any predications regarding such mutations with any reasonable expectation of success nor envisage the breadth of structurally unrelated CDR combinations that would result in an antibody that can bind to galectin-3. Further, the amount of experimentation to require to formulate each antibody with such guidance would be enormous. One would have to demonstrate the binding affinity and specificity to galectin-3 of each variation that contain 1-5 amino acid residue changes within the 6 CDRs of the antibody.
Conclusion
Thus, considering the high level of skill in the art, the state of the art, the level of predictability, and the guidance and examples provided, the experimentation required to enable the full scope of the claimed invention would not be reasonable. As indicated by the art, a full complement of 6 CDRs are required for antigen binding and one cannot predict which CDR residues may be changed and still result in an antibody that binds galectin 3. Enablement can be met if the claims recite the minimal structure of the antibody as recited in claim 1 and shown in FIG. 2A of the instant disclosure drawings, that is the claims would need to recite the 6 CDRs in the antibody that bind galectin 3 antigen, without variability in the sequences thereof.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-2,5,7,9,11,13,15,18,22-23,26-27,29,35,37-39,42-43,45,48-49,52-54,62-64,68-69,72-73,76-77,88,102,104,108 and 110-111 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent 11,427,638, published August 30th, 2022 (herein “Sun”) and further in view of WO 2018/204374, published on November 8th, 2018 (herein “Desai”), Kang (Kang, Jichao , et al. “Rapid Formulation Development for Monoclonal Antibodies.” Www.bioprocessintl.com, BioProcess International, 12 Apr. 2016, www.bioprocessintl.com/formulation/rapid-formulation-development-for-monoclonal-antibodies. Accessed 26 June 2026), Srejovic (Srejovic et al. Galectin-3: Roles in Neurodevelopment, Neuroinflammation, and Behavior. Biomolecules. 2020; 10(5):798. https://doi.org/10.3390/biom10050798) and as evidenced by Expasy Translate Tool (Expasy Translate Tool for instant SEQ ID NOs: 12-15 (https://web.expasy.org/translate/)). It is noted that Sun names the same Applicant (“TrueBinding, Inc.”) and same inventor (“Sun, Dongxu”). However, Sun also names other inventors that is different from the instant application (“Wang, Yan”, “Wu, Yinan”, “Gordon, Catherine A.”, and “Williams, Samuel A.F.”) and the earliest effective filing date of Sun is January 30th, 2019 from provisional applications 62/798,949 and 62/798,945 and is more than 1 year older than the effective filing date of the instant application. Therefore, Sun is considered as prior art under 35 U.S.C. 102(a)(2). See MPEP 2154.01.
Regarding claim 1, 26, 37, 42, and 102, Sun teaches the pharmaceutical antibody formulation comprising a therapeutically effective amount of an antibody, wherein the antibody comprises a heavy chain CDR1 (HCDR1) having the sequence of SEQ ID NO: 2, a heavy chain CDR2 (HCDR2) having the sequence of SEQ ID NO: 3, a heavy chain CDR3 (HCDR3) having the sequence of SEQ ID NO: 4, a light chain CDR1 (LCDR1) having the sequence of SEQ ID NO: 5, a light chain CDR2 (LCDR2) having the sequence of SEQ ID NO: 6; and a light chain CDR3 (LCDR3) having the sequence of SEQ ID NO: 7 (Drawings, page 52-53, Fig 35A-B, Figure 1 and 2 of this office action).
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Figure 1. Sun, drawings, page 52, Fig 35A showing HCDR1-3 sequences
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Figure 2. Sun, drawings, page 53, Fig. 35B showing LCDR1-3 sequences
Sun further teaches pharmaceutical compositions (page 97, column 53, line 41-43, “a pharmaceutical formulation for reducing tissue fibrosis can comprise an anti-Gal3 antibody described supra.”). While Sun discloses pharmaceutically acceptable carriers for NaCl to maintain osmolarity of the formulation, buffers to provide pH control or maintenance, sugars as cryoprotectant and polysorbate to prevent aggregation (page 97, column 54, line 17-23, “pharmaceutical compositions include one or more salts in an amount required to bring osmolality of the composition into an acceptable range. Such salts include […] sodium chloride”; line 7-16 “pH adjusting agents or buffering agents […] Such acids, bases and buffers are included in an amount required to maintain pH of the composition in an acceptable range”; page 80, column 20, line 1-5, “Examples include, but are not limited to, any of the standard pharmaceutical carriers such as a phosphate buffered saline solution, water, emulsions such as oil/water emulsion, various types of wetting agents, detergents such as polysorbate 20 to prevent aggregation, and sugars such as sucrose as cryoprotectant”), Sun does not teach the pharmaceutical composition comprises histidine, methionine, and the pH is between 5.3 and 6.3. Furthermore, Sun does not teach the specific concentration ranges of each excipient recited in instant claims 2, 5, 7, 11, 13, 15, 23, 26, 29, 37, and 102.
Desai teaches a pharmaceutical antibody formulation for another antibody specific for LAG3 that comprises histidine, methionine, NaCl, sucrose, polysorbate80, histidine, and the pH is 5.8-6.0 (page 3, line 8-11, “In one aspect, the invention provides one or more of an excipient selected from the group consisting of histidine, aspartate, glutamine, glycine, proline, methionine, arginine or a pharmaceutically acceptable salt thereof, NaCl […] at a total concentration of 10-1000 mM, and a buffer at pH about 5-8” and line 17-20, “In a further embodiment, the formulation comprises about 25 mg/mL anti-LAG3 antibody; about 50 mg/mL sucrose; about 0.2 mg/mL polysorbate 80; about 10 mM L-histidine buffer at about pH 5.8-6.0; about 70 mM L-Arginine-HCl thereof; and optionally about 10 mM L-methionine”).
Desai further teaches that the antibody formulation is stable over months to years under conditions typical for storage for drugs for self-administration, i.e. at refrigerator temperature in a syringe, resulting in a long shelf-life for the corresponding drug product (page 5, line 1-3). As a teaching reference, Kang teaches that “although every antibody is unique, the molecules are highly similar structurally” (page 40, column 2, paragraph 1). Kang further summarizes and reviews excipients that are used successfully in commercially available antibody formulations (page 41, Table 1, and page 40, column 2, paragraph 1, “Lessons learned from successful examples are invaluable in developing stable and effective formulations for new MAbs”).
Therefore, it would have been obvious to the person of ordinary skill in the art to use the excipients taught by Desai and Kang to form antibody formulations of the anti-Gal3 antibody recited by Sun to keep the formulation stable for long term storage.
It would further be obvious that the compound dosage in a composition is clearly a result effective parameter that a person having ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been obvious for an artisan of ordinary skill to determine the optimal amount of each ingredient, i.e., the dosage and dosing regimen, needed to achieve the desired results. The principle of law states from MPEP §§ 2144.05: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages," (see In re Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382). Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation," (See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)).
Regarding instant claim 2, Desai teaches L-histidine concentration at less than 40 mM which is within range of the instant claims (page 64, Table 4, and see figure 3 of this office action).
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Figure 3. Desai teaches the formulation of the antibody (page 64, Table 4)
Regarding instant claim 5, Desai teaches the methionine concentration to be optimal at 10 mM but also teaches the range from 5 mM to 10 mM to be colloidally stabilizing the antibody (page 76, line 9-12, “L-methionine (5 mM to 10 mM) was found to colloidally stabilize anti-LAG3 (25 mg/mL anti-LAG3, 10 mM L-histidine, 70 mM L-arginine, 5% w/v sucrose, pH 5.8) in comparison to the control as listed in Table 8; with 10 mM L-methionine as the optimal amount”).
Regarding instant claim 7, Desai teaches the sodium chloride concentration of 40 to 100 mM to have improved chemical stability (page 63, line 15-17, “Sodium chloride showed an improvement in chemical stability in the concentration range of 40 to 100 mM, especially at [less than or equal to] 70 mM concentration” and page 64, table 4, figure 3 of this office action). Further, Desai teaches the pH is about 5.8 (page 64, Table 4, Figure 3 of this office action).
Regarding instant claim 9 and 11, Desai teaches the polysorbate 80 concentration (page 74, line 9-12, “In the presence of 0.1 mg/mL to 1.0 mg/mL polysorbate 80 concentrations in the formulation matrix (25 mg/mL anti-LAG3 in 10 mM L-histidine, 70 mM L-arginine hydrochloride, 5% w/v sucrose, pH 5.8), anti-LAG3 was found to be stable”). Further, Desai teaches that the polysorbate 80 concentration is at 0.01% (page 73, table 7, figure 4 of this office action).
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Figure 4. page 73, Table 7)
Regarding instant claim 13, Desai teaches the pH is about 5.8 (page 73, Table 7, Figure 4 of this office action).
Regarding instant claim 15 and 29, Desai teaches the sucrose is at 5% w/v (page 80, line 1-2, “of 200 mg/mL anti-LAG3 was comparatively high in the presence of 5% w/v sucrose”). Desai also teaches polyols that comprise mannitol as recited in claim 29 (page 33, line 8-15, “the polyol is selected from the group consisting of mannitol” and “the polyol is at a concentration of 10-200 mg/ml”).
Regarding instant claims 18, 22, 23, 26, 27, 35, 39, 49, 52, 53, 54, 102, 104, 110, and 111, Desai teaches an antibody is present at a concentration of 25 mg/ml (page 73, table 7, figure 10 of this office action) and concentration can be as high as 500 mg/ml (page 48, line 30-32, “The protein may be reconstituted at a concentration of about 10, 15, 20, 25, 30, 40, 50, 60, 75, 80, 90 or 100 mg/mL or higher concentrations such as 150 mg/mL, 200 mg/mL, 250 mg/mL, or 300 mg/mL up to about 500 mg/mL”).
Sun teaches that the anti-Gal3 antibody is administered to a patient at 10 mg/kg of the patient’s body weight (page 110, column 79, line 44-45).
Regarding the recited dilutions prior to administration in instant claims 52, 53, 54, 110, and 111, Desai further discloses methods to determine therapeutically effective doses (page 51, line 31-33, “The data obtained from these cell culture assays and animal studies can be used in formulating a range of dosage for use in human. The dosage of such compounds lies preferably within a range of circulating concentrations that include the ED50 with little or no toxicity” and page 52, line 1-7, “The appropriate dosage ("therapeutically effective amount") of the protein will depend, for example, on the condition to be treated, the severity and course of the condition, whether the protein is administered for preventive or therapeutic purposes, previous therapy, the patient's clinical history and response to the protein, the type of protein used, and the discretion of the attending physician. Generally, the dose begins with an amount somewhat less than the optimum dose and it is increased by small increments thereafter until the desired or optimum effect is achieved relative to any negative side effects”).
Further, Desai teaches high concentrations solution formulations can be used for lower concentrations which means that the doses can be diluted to administer at lower doses (page 51, line 25-31 “Although the high concentration solution formulations of the present invention are particularly advantageous for uses requiring a high concentration of antibody, there is no reason that the formulations can't be used at lower concentrations in circumstances where high concentrations are not required or desirable. Lower concentrations of antibody may be useful for low dose subcutaneous administration, or in other modes of administration (such as intravenous administration) where the volume that can be delivered is substantially more than 1 ml. Such lower concentrations can include 15, 10, 5, 2, 1 mg/ml or less.”)
Further, Desai teaches that “selecting an administration regimen for a therapeutic depends on several factors, including the serum or tissue turnover rate of the entity, the level of symptoms, the immunogenicity of the entity, and the accessibility of the target cells in the biological matrix. Preferably, an administration regimen maximizes the amount of the therapeutic delivered to the patient consistent with an acceptable level of side effects.” (page 50, line 17-22)
Based on Desai’s teaching of antibody formulation and concentrations and Sun’s therapeutic dose of the anti-Gal3 antibody, one of ordinary skill in the art would have been able to optimize the unit dose and dilutions needed to administer a therapeutically effective dose of the antibody to the subject with reasonable expectation of success at balancing effective dosing and minimizing undesirable side effects. In regards to the specific dosage and interval amounts recited in the instant claims "[w]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955), and see M.P.E.P. § 2144.05 II.A. Moreover, it is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804,809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989). This because, as is made clear from the prior art, the determination of the dosage regimen of a known drug is well within the purview of one of ordinary skill in the art at the time the invention was made, and it would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal intervals of treatment because optimal intervals is an art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art. Therefore, it would be conventional and within the skill of the art to identify the optimal dosages administered and optimal intervals to achieve target levels and therapeutically effective doses. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. It is clear that both the prior art and claimed method perform the same protocol to achieve the same results. It would be conventional and within the skill of the art to determine the optimal treatment regimens. Accordingly, one can see that the courts, over a period of over 50 years, have consistently held that treatment (i.e. dosage and intervals) optimization is obvious.
Regarding the recited unit doses in instant claims 18, 23, 26, 27, 39, 45, 102, 104, 108, Desai teaches the range of doses that the pharmaceutical antibody composition can be formulated to achieve the desired concentrations and which is intended to be administered by injection device or vessel (Desai, page 48, line 16-20). Further, Sun teaches a dose for a subject as described prior. Therefore, it would have been obvious to a person of ordinary skill in the art to formulate and optimize the unit doses to achieve maximal therapeutic effective dosages in a subject based on Sun’s teaching of the anti-Gal3 antibody and Desai’s stable pharmaceutical antibody formulation.
Regarding instant claim 42 and 45, Desai teaches that the pharmaceutical antibody formulation is packaged in a sterile glass vial (page 55, line 19-20, “The drug product was packaged in a single-use, sterile 2 mL Type 1 glass tubing vial with a 13-mm elastomeric stopper and aluminum seal with plastic flip-off cap. Each vial contains a label claim of 50 mg (2.2 mL fill) at a concentration of 25 mg/mL”).
Regarding instant claims 62, 63, and 64, Sun teaches the VH and VL sequences (drawings, page 55 and 57, Fig 36A and 36B cont. See figure 5 and 6 of this office action)
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Figure 5. Sun teaches the VH sequences (page 55 of drawings, Fig. 36A cont.)
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Figure 6. Sun teaches the VL sequences (page 57 of drawings, Fig. 36B cont.)
Regarding instant claims 68 and 69, Sun teaches the amino acid sequences of the heavy chain and light chains (Drawings, page 58, Fig. 37, See figure 7 of this office action).
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Figure 7 Sun teaches the amino acid sequences of the HC and LC of the claimed antibody (drawings, page 58, Fig. 37)
Regarding instant claims 72 and 73, Sun teaches the nucleic acid sequences for VH and VL of the instant claims because the nucleic acid sequences translate to the amino acid sequences as taught by Sun (Expasy Translate Tool (https://web.expasy.org/translate/) SEQ ID NO: 12, page 2) of instant SEQ ID NO: 12 discloses the amino acid sequence of SUN’s SEQ ID NO 229 (See Figure 5 of this office action). Accordingly, the nucleic acid sequences of the instant SEQ ID NO: 13 translated using Expasy Translate tool resulted in the same amino acid sequence as taught by Sun (page 2 of Expasy tool translate for SEQ ID NO: 13 and VL sequence of Sun (page 57 of drawings, Fig. 36B cont.)).
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Figure 8. Expasy Translation tool of instant SEQ ID NO: 12 translated to amino acids aligns with Sun's amino acid sequence, Sun teaches the VH sequences (page 55 of drawings, Fig. 36A cont.)
Regarding instant claims 76 and 77, as described previously the SEQ ID NO: 14 and 15 are nucleic acid sequences of the HC and LC respectively. When translated, SEQ ID NO: 14 and 15 are taught by Sun (Drawings, page 58, Fig. 37, See figure 7 of this office action, see Expasy Translate Tool for SEQ ID NO: 14 and 15, page 2).
Regarding instant claim 88, Sun teaches the antibody binding affinity of the anti-Gal3 antibodies was assessed using biolayer interferometry (page 108, column 75, line 64-67) and discloses the kD of the antibody at 1.2 nM (page 108, column 76, line 8-10), but does not teach that the kD of the antibody is between 1.7-4.2 nM when stored at a) 40°C for 7, 14, 21, or 28 days, b) 25°C for 14 days or 1, 3, 6, or 9 months, c) 4°C for 1, 3, 6, 9, 12, or 18 months, or d) -80°C for 1, 3, 6, 9, 12, or 18 months, and/or after being subjected to shear stress or freeze thaws, optionally 3 or 5 freeze thaws. Desai teaches the antibody is developed to be frozen or refrigerated (page 55, line 13-16, “developed as either frozen drug product (recommended storage at <-70°C) or refrigerated drug product (recommended storage at 2 to 8°C) and stability studies were conducted in the below examples”). Further, Desai teaches that the diffusion interaction parameter (kD) is assessed using dynamic light scattering (DLS) (page 61, line 8-9, “The diffusion interaction parameter (kD) of the nine formulations were assessed using dynamic light scattering (DLS) at 20°C for five acquisitions” and page 103, figure 15 depicting the kD constant is between 1.7 and 4.2”, see figure 9 of this office action).
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Figure 9. Desai, Fig 15. page 103, teaching the kD of the antibody formulation).
However, Sun does not teach the method of treating Alzheimer’s disease, comprising administering the pharmaceutical antibody formulation to a subject in need of Alzheimer’s disease treatment as recited in instant claim 102 and 108.
Srejovic teaches that galectin-3 “plays an important role in the pathogenesis of neuroinflammatory and neurogenerative disorders such as multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease” (page 1, abstract). Srejovic further teaches anti-Gal3 antibody that is neuroprotective and decreases pro-inflammatory markers and attenuated microglial activation (page 9, paragraph 1, “Application of anti-Gal-3 antibody exhibited neuroprotective effect due to decreased trauma-induced synthesis of proinflammatory markers, IL-1b, IL-6 and iNOS, and attenuated microglial activation”). Finally, Srejovic further discloses that the galectin-3 can be used as a therapeutic target in a variety of pathological conditions as an immunomodulator (page 13, paragraph 1). Therefore, it would have been obvious to the person of ordinary skill in the art to use the pharmaceutical formulation of the antibody as recited in Sun and Desai to treat Alzheimer’s taught by Srejovic. One of ordinary skill in the art would have been motivated to substitute the method of treating fibrosis using the anti-Gal3 antibody taught by Sun with the method of treating Alzheimer’s because galectin 3 is a therapeutic target in Alzheimer’s as taught by Srejovic.
Regarding instant claims 110 and 111, Desai teaches methods to administer the antibody formulation and that the determination of the appropriate dose is made by the clinician, e.g., using parameters or factors known or suspected in the art to affect treatment or predicted to affect treatment (page 51, line 1-5, and line 11-14, “Antibodies, or antibody fragments can be provided by continuous infusion, or by doses at intervals of, e.g., one day, 1-7 times per week, one week, two weeks, three weeks, monthly, bimonthly, etc. A preferred dose protocol is one involving the maximal dose or dose frequency that avoids significant undesirable side effects”). "In regards to the specific dosage and interval amounts recited in the instant claims "[w]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955), and see M.P.E.P. § 2144.05 II.A. Moreover, it is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804,809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989). This because, as is made clear from the prior art, the determination of the dosage regimen of a known drug is well within the purview of one of ordinary skill in the art at the time the invention was made, and it would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal intervals of treatment because optimal intervals is an art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art. Therefore, it would be conventional and within the skill of the art to identify the optimal dosages administered and optimal intervals to achieve target levels and therapeutically effective doses. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. It is clear that both the prior art and claimed method perform the same protocol to achieve the same results. It would be conventional and within the skill of the art to determine the optimal treatment regimens. Accordingly, one can see that the courts, over a period of over 50 years, have consistently held that treatment (i.e. dosage and intervals) optimization is obvious."
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.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
U.S. Patents
Claims 1-2,5,7,9,11,13,15,18,22-23,26-27,29,35,37-39,42-43,45,48-49,52-54,62-64,68-69,72-73,76-77,88,102,104,108 and 110-111 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-5 of U.S. Patent No. 11,427,638 B2, issued on August 3rd, 2022 (herein “Patent‘638” and “Sun” as referenced prior) in view of WO 2018/204374, published on November 8th, 2018 (herein “Desai”), Srejovic (Srejovic I, Selakovic D, Jovicic N, Jakovljević V, Lukic ML, Rosic G. Galectin-3: Roles in Neurodevelopment, Neuroinflammation, and Behavior. Biomolecules. 2020; 10(5):798. https://doi.org/10.3390/biom10050798), and Domnowski (Domnowski M, Hackner B, Neuber T, Jaehrling J, Frieß W. Analysis of antibody self-interaction by bio-layer interferometry as tool to support lead candidate selection during preformulation and developability assessments. Int J Pharm. 2020 Nov 15;589:119854. doi: 10.1016/j.ijpharm.2020.119854. Epub 2020 Sep 6. PMID: 32898632).
Patent’638 claim 1 recites the antibody with 100% identity to the 6 CDRs and VH and VL as well as HC and LC as the instant claims 1, 26, 37, 42, and 102. Specifically, instant claim 1, 26, 37, 42, 102, recite the HCDR1-3 with the SEQ ID NOs: 2,3, and 4 and LCDR1-3 with the SEQ ID NOs: 5,6, and 7. The patented claim 1 recite the same HCDR1-3 and LCDR1-3 with the SEQ ID NOs: 62,90, 118 and SEQ ID NOs: 146, 174 and 202 as shown in the figures 10,11,12, 13, 14, 15 of this office action.
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Figure 10. Patent’638 claim 1, SEQ ID NO: 62, page 119
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Figure 11. Patent’638 Claim 1, SEQ ID NO: 90, page 129
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Figure 12. Patent’638 claim 1, SEQ ID NO: 118, page 137
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Figure 13. Patent’638 Claim 1, SEQ ID NO: 146, page 147
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Figure 14. Patent’638 claim 1, SEQ ID NO: 174, page 156-157
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Figure 15. Patent’638 claim 1, SEQ ID NO: 202, page 165
Regarding instant claims 62, 63, and 64, Patent’638 claim 2 and 4 recite the VH region instant SEQ ID NO: 8 and VL region instant SEQ ID NO: 9 (Claim 2 and 4 of patent, VH SEQ ID NO: 230 and VL SEQ ID NO: 258 and see figure 16 and 17 of this office action). Instant claim 72 and 73 recite the VH and VL that is encoded by nucleic acid sequences SEQ ID NO: 12 and 13 which translated to amino acids results in the same sequences as instant SEQ ID NO: 8 and 9. Therefore, Patent’638 claims 2 and 4 also recite the nucleic acid sequences in instant claims 72 and 73 (see previous analysis of claims 72 and 72 rejection above).
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Figure 16. Patent’638 claim, SEQ ID NO: 230,
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Figure 17. Patent’638 claim, VL of SEQ ID NO 258
Regarding instant claims 68 and 69, instant SEQ ID NO: 10 and 11 has 100% identity to SEQ ID NO: 265 and 266 of Patent’638 claims 3 and 5. Instant claim 76 and 77 recite the HC and LC that is encoded by nucleic acid sequences SEQ ID NO: 14 and 15. Instant claim 76 and 77 recite the HC and LC that is encoded by nucleic acid sequences SEQ ID NO: 14 and 15 which translated to amino acids results in the same sequences as instant SEQ ID NO: 10 and 11. Therefore, Patent’638 claims 2 and 4 also recite the nucleic acid sequences in instant claims 76 and 77 (see prior rejection of claims 76 and 77 above).
However, Patent’638 claims do not recite the pharmaceutical formulation of the antibody as recited in instant claims 1, 2, 5, 7, 9, 11, 13, 15, 22, 23, 26, 29, 37, 38, and 102.
Desai teaches the sodium chloride concentration of 40 to 100 mM to have improved chemical stability (page 63, line 15-17, “Sodium chloride showed an improvement in chemical stability in the concentration range of 40 to 100 mM, especially at [less than or equal to] 70 mM concentration” and page 64, table 4, Figure 18 of this office action). Further, Desai teaches the pH is about 5.8 (page 64, Table 4, Figure 18 of this office action).
Desai teaches the methionine concentration to be optimal at 10 mM but also teaches the range from 5 mM to 10 mM to be colloidally stabilizing the antibody (page 76, line 9-12, “L-methionine (5 mM to 10 mM) was found to colloidally stabilize anti-LAG3 (25 mg/mL anti-LAG3, 10 mM L-histidine, 70 mM L-arginine, 5% w/v sucrose, pH 5.8) in comparison to the control as listed in Table 8; with 10 mM L-methionine as the optimal amount”).
Desai teaches the sucrose is at 5% w/v (page 80, line 1-2, “of 200 mg/mL anti-LAG3 was comparatively high in the presence of 5% w/v sucrose”). Desai also teaches polyols that comprise mannitol as recited in claim 29 (page 33, line 8-15, “the polyol is selected from the group consisting of mannitol” and “the polyol is at a concentration of 10-200 mg/ml”).
Desai teaches L-histidine concentration at less than 40 mM which is within range of the instant claims (page 62, line 1-4, “A positive diffusion interaction parameter(kD) is suggestive of repulsive interaction. With increasing concentration (> 40 mM) of L-arginine, L-histidine or sodium chloride, anti-LAG3 shows increase in kd suggesting reduction of molecular self-association (less molecular crowding)”).
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Figure 18. Desai teaches the formulation of the antibody (page 64, Table 4)
Desai teaches the polysorbate 80 concentration (page 74, line 9-12, “In the presence of 0.1 mg/mL to 1.0 mg/mL polysorbate 80 concentrations in the formulation matrix (25 mg/mL anti-LAG3 in 10 mM L-histidine, 70 mM L-arginine hydrochloride, 5% w/v sucrose, pH 5.8), anti-LAG3 was found to be stable”). Further, Desai teaches that the polysorbate 80 concentration is at 0.01% (page 73, table 7, figure 10 of this office action).
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Figure 19. page 73, Table 7)
Desai finally teaches that the antibody formulation is stable over months to years under conditions typical for storage for drugs for self-administration, i.e. at refrigerator temperature in a syringe, resulting in a long shelf-life for the corresponding drug product (page 5, line 1-3). Therefore, it would have been obvious to the person of ordinary skill in the art to use the excipients taught by Desai to form antibody formulations of the anti-Gal3 antibody recited by Pat’638 to keep the formulation stable for long term storage.
However, Patent’638 claims do no recite the unit doses of the antibody formulation as recited in instant claim 18, 23, 26, 27, 35, 39, 102, 104, 110, and 111.
Desai teaches an antibody is present at a concentration of 25 mg/ml (page 73, table 7, figure 10 of this office action) and concentration can be as high as 500 mg/ml (page 48, line 30-32, “The protein may be reconstituted at a concentration of about 10, 15, 20, 25, 30, 40, 50, 60, 75, 80, 90 or 100 mg/mL or higher concentrations such as 150 mg/mL, 200 mg/mL, 250 mg/mL, or 300 mg/mL up to about 500 mg/mL.”)
Desai further discloses methods to determine therapeutically effective doses (page 51, line 31-33, “The data obtained from these cell culture assays and animal studies can be used in formulating a range of dosage for use in human. The dosage of such compounds lies preferably within a range of circulating concentrations that include the ED50 with little or no toxicity” and page 52, line 1-7, “The appropriate dosage ("therapeutically effective amount") of the protein will depend, for example, on the condition to be treated, the severity and course of the condition, whether the protein is administered for preventive or therapeutic purposes, previous therapy, the patient's clinical history and response to the protein, the type of protein used, and the discretion of the attending physician. Generally, the dose begins with an amount somewhat less than the optimum dose and it is increased by small increments thereafter until the desired or optimum effect is achieved relative to any negative side effects.”). Desai also teaches the dose regimen of antibodies (page 53, line 11-14, “Antibodies, or antibody fragments can be provided by continuous infusion, or by doses at intervals of, e.g., one day, 1-7 times per week, one week, two weeks, three weeks, monthly, bimonthly, etc. A preferred dose protocol is one involving the maximal dose or dose frequency that avoids significant undesirable side effects.”)
In regards to the specific dosage and interval amounts recited in the instant claims "[w]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955), and see M.P.E.P. § 2144.05 II.A. Moreover, it is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804,809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989). This because, as is made clear from the prior art, the determination of the dosage regimen of a known drug is well within the purview of one of ordinary skill in the art at the time the invention was made, and it would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal intervals of treatment because optimal intervals is an art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art. Therefore, it would be conventional and within the skill of the art to identify the optimal dosages administered and optimal intervals to achieve target levels and therapeutically effective doses. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. It is clear that both the prior art and claimed method perform the same protocol to achieve the same results. It would be conventional and within the skill of the art to determine the optimal treatment regimens. Accordingly, one can see that the courts, over a period of over 50 years, have consistently held that treatment (i.e. dosage and intervals) optimization is obvious.
However, the Patent’638 claims do not recite a sterile vial comprising the pharmaceutical antibody formulation as recited in instant claims 42, 43, 45, 48, 49, 52, 53, and 54. Desai teaches that the pharmaceutical antibody formulation is packaged in a sterile glass vial (page 55, line 19-20, “The drug product was packaged in a single-use, sterile 2 mL Type I glass tubing vial with a 13-mm elastomeric stopper and aluminum seal with plastic flip-off cap. Each vial contains a label claim of 50 mg (2.2 mL fill) at a concentration of 25 mg/mL”).
However, the Patent’638 claims do not recite the pharmaceutical antibody formulation wherein the formulation exhibits a dissociation constant (KD) of 1.7-4.2 or about 1.7-4.2 as determined by biolayer interferometry (BLI) when stored at a) 40°C for 7, 14, 21, or 28 days, b) 25°C for 14 days or 1, 3, 6, or 9 months, c) 4°C for 1, 3, 6, 9, 12, or 18 months, or d) -80°C for 1, 3, 6, 9, 12, or 18 months, and/or after being subjected to shear stress or freeze thaws, optionally 3 or 5 freeze thaws as recited in instant claim 88.
Desai teaches the antibody is developed to be frozen or refrigerated (page 55, line 13-16, “developed as either frozen drug product (recommended storage at <-70°C) or refrigerated drug product (recommended storage at 2 to 8°C) and stability studies were conducted in the below examples”) using . Further, Desai teaches that the diffusion interaction parameter (kD) is assessed using dynamic light scattering (DLS) (page 61, line 8-9, “The diffusion interaction parameter (kD) of the nine formulations were assessed using dynamic light scattering (DLS) at 20°C for five acquisitions” and page 103, Fig. 15 depicting the kD constant is between 1.7 and 4.2”, see figure 20 of this office action).
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Figure 20. Desai page 103, figure 15
However, Desai doesn’t teach the method of measuring kD is by using biolayer interferometry. Domnowski teaches that the bio-layer interferometry can be used instead of dynamic light scattering (DLS) measurements (page 1, abstract) and that the BLI can be performed in high throughput with minimal material and sample preparation needs. Therefore, it would have been obvious to the person of ordinary skill in the art to substitute DLS with BLI to perform high throughput analysis of antibody with minimal material and sample preparation.
However, Patent’638 claims do not recite the method of treating Alzheimer’s disease, comprising administering the pharmaceutical antibody formulation to a subject in need of Alzheimer’s disease treatment as recited in instant claim 102 and 108.
Srejovic teaches that galectin-3 “plays an important role in the pathogenesis of neuroinflammatory and neurogenerative disorders such as multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease” (page 1, abstract). Srejovic further teaches anti-Gal3 antibody that is neuroprotective and decreases pro-inflammatory markers and attenuated microglial activation (page 9, paragraph 1, “Application of anti-Gal-3 antibody exhibited neuroprotective effect due to decreased trauma-induced synthesis of proinflammatory markers, IL-1b, IL-6 and iNOS, and attenuated microglial activation”). Finally, Srejovic further discloses that the galectin-3 can be used as a therapeutic target in a variety of pathological conditions as an immunomodulator (page 13, paragraph 1). Therefore, it would have been obvious to the person of ordinary skill in the art to use the pharmaceutical formulation of the antibody as recited in the instant claim to treat Alzheimer’s. One of ordinary skill in the art would have been motivated to use the anti-Gal3 antibody in the Pat’638 claims in the method of treating Alzheimer’s recited in instant claims because galectin 3 is a therapeutic target in Alzheimer’s as taught by Srejovic.
Claims 1-2,5,7,9,11,13,15,18,22-23,26-27,29,35,37-39,42-43,45,48-49,52-54, 88,102,104,108 and 110-111 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 12,281,166 B2, issued on April 22nd, 2025 (herein “Pat’166”) in view of Desai (cited previously), Srejovic (cited previously), and Domnowski (cited previously).
Pat’166 claim 1 recites the LCDR1-3 (SEQ ID: 171, 222, 249) and HCDR1-3 (SEQ ID NO: 31, 72, 113) sequences that are 100% match with the sequences recited in the instant claim 1, 26, 37, 42, and 102. It is noted that Pat’458 claims do not teach the VH, VL, HC, LC sequences as recited in instant claims 62, 63, 64, 68, 69, 72, 73, 76, and 77.
However, Patent’166 claims do not recite the pharmaceutical formulation of the antibody as recited in instant claims 1, 2, 5, 7, 9, 11, 13, 15, 22, 23, 26, 29, 37, 38, and 102.
As described previously in the nonstatutory double patenting rejection of Pat’638, Desai teaches the pharmaceutical antibody formulation and the excipients. Therefore, it would have been obvious to the person of ordinary skill in the art to formulate the antibody formulation of the anti-Gal3 antibody in the Pat’166 claims with Desai’s teachings to formulate stable antibody formulation for long term storage.
However, Patent’166 claims do no recite the unit doses of the antibody formulation as recited in instant claim 18, 23, 26, 27, 35, 39, 102, 104, 110, and 111.
As described previously, Desai teaches methods in determining the therapeutically effective dose of the antibody and formulations that allow administration of the antibody. In regards to the specific dosage and interval amounts recited in the instant claims "[w]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955), and see M.P.E.P. § 2144.05 II.A. Moreover, it is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804,809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989). This because, as is made clear from the prior art, the determination of the dosage regimen of a known drug is well within the purview of one of ordinary skill in the art at the time the invention was made, and it would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal intervals of treatment because optimal intervals is an art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art. Therefore, it would be conventional and within the skill of the art to identify the optimal dosages administered and optimal intervals to achieve target levels and therapeutically effective doses. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. It is clear that both the prior art and claimed method perform the same protocol to achieve the same results. It would be conventional and within the skill of the art to determine the optimal treatment regimens. Accordingly, one can see that the courts, over a period of over 50 years, have consistently held that treatment (ie dosage and intervals) optimization is obvious.
However, the Patent’166 claims do not recite a sterile vial comprising the pharmaceutical antibody formulation as recited in instant claims 42, 43, 45, 48, 49, 52, 53, and 54. As described previously, Desai teaches that the pharmaceutical antibody formulation is packaged in a sterile glass vial (page 55, line 19-20).
However, the Patent’166 claims do not recite the pharmaceutical antibody formulation wherein the formulation exhibits a dissociation constant (KD) of 1.7-4.2 or about 1.7-4.2 as determined by biolayer interferometry (BLI) when stored at a) 40°C for 7, 14, 21, or 28 days, b) 25°C for 14 days or 1, 3, 6, or 9 months, c) 4°C for 1, 3, 6, 9, 12, or 18 months, or d) -80°C for 1, 3, 6, 9, 12, or 18 months, and/or after being subjected to shear stress or freeze thaws, optionally 3 or 5 freeze thaws as recited in instant claim 88. As described previously, Desai teaches storage conditions of the antibody formulation as well as stability studies that allow refrigeration and freezing of the formulation by using DLS to measure Kd. However, Desai does not teach the Kd is measured by bio-layer interferometry. As described previously, Domnowski teaches the BLI can be used instead of DLS to allow high throughput performance with minimal preparation. Therefore, it would have been obvious to the person of ordinary skill in the art to substitute DLS with BLI to perform high throughput analysis of antibody with minimal material and sample preparation.
However, Patent’166 claims do not recite the method of treating Alzheimer’s disease, comprising administering the pharmaceutical antibody formulation to a subject in need of Alzheimer’s disease treatment as recited in instant claim 102 and 108.
As described previously, Srejovic teaches that galectin-3 “plays an important role in the pathogenesis of neuroinflammatory and neurogenerative disorders such as multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease” (page 1, abstract). Srejovic further teaches anti-Gal3 antibody that is neuroprotective and decreases pro-inflammatory markers and attenuated microglial activation (page 9, paragraph 1). Finally, Srejovic further discloses that the galectin-3 can be used as a therapeutic target in a variety of pathological conditions as an immunomodulator (page 13, paragraph 1). Therefore, it would have been obvious to the person of ordinary skill in the art to use the pharmaceutical formulation of the antibody as recited in the instant claim to treat Alzheimer’s. One of ordinary skill in the art would have been motivated to use the anti-Gal3 antibody in the Pat’166 claims in the method of treating Alzheimer’s recited in instant claims because galectin 3 is a therapeutic target in Alzheimer’s as taught by Srejovic.
Claims 1-2,5,7,9,11,13,15,18,22-23,26-27,29,35,37-39,42-43,45,48-49,52-54, 88,102,104,108 and 110-111 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 12,497,458 B2, issued on December 16th, 2025 (herein “Pat’458”) in view of in view of Desai (cited previously), Srejovic (cited previously), and Domnowski (cited previously).
Pat’458 claim 1 recites the antibody comprising the VH CDR1-3 amino acid sequence that is 100% match with the HCDR1-3 recited in the instant claim 1, 26, 37, 42, and 102. (Pat’458 claim 1,“VH-CDR1 comprises an amino acid sequence comprising SEQ ID NO: 39, the VH-CDR2 comprises an amino acid sequence comprising SEQ ID NO: 67, the VH-CDR3 comprises an amino acid sequence comprising SEQ ID NO: 95”) and VL CDR1-3 amino acid sequence that is 100% match with the LCDR1-3 recited in the instant claims 1, 26, 37, 42, and 102 (Pat’458 claim 1, “the VL-CDR1 comprises an amino acid sequence comprising SEQ ID NO: 121, the VL-CDR2 comprises an amino acid sequence comprising RMS, the VL-CDR3 comprises an amino acid sequence comprising SEQ ID NO: 177”).
It is noted that Pat’458 claims do not teach the VH, VL, HC, LC amino acid and nucleic acid sequences as recited in instant claims 62, 63, 64, 68, 69, 72, 73, 76, and 77.
However, Pat’458 claims do not recite the pharmaceutical formulation of the antibody as recited in instant claims 1, 2, 5, 7, 9, 11, 13, 15, 22, 23, 26, 29, 37, 38, and 102.
As described previously in the nonstatutory double patenting rejection of Pat’638, Desai teaches the pharmaceutical antibody formulation and the excipients. Therefore, it would have been obvious to the person of ordinary skill in the art to formulate the antibody formulation of the anti-Gal3 antibody in the Pat’458 claims with Desai’s teachings to formulate stable antibody formulation for long term storage.
However, Pat’458 claims do no recite the unit doses of the antibody formulation as recited in instant claim 18, 23, 26, 27, 35, 39, 102, 104, 110, and 111.
As described previously, Desai teaches methods in determining the therapeutically effective dose of the antibody and formulations that allow administration of the antibody. In regards to the specific dosage and interval amounts recited in the instant claims "[w]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955), and see M.P.E.P. § 2144.05 II.A. Moreover, it is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804,809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989). This because, as is made clear from the prior art, the determination of the dosage regimen of a known drug is well within the purview of one of ordinary skill in the art at the time the invention was made, and it would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal intervals of treatment because optimal intervals is an art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art. Therefore, it would be conventional and within the skill of the art to identify the optimal dosages administered and optimal intervals to achieve target levels and therapeutically effective doses. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. It is clear that both the prior art and claimed method perform the same protocol to achieve the same results. It would be conventional and within the skill of the art to determine the optimal treatment regimens. Accordingly, one can see that the courts, over a period of over 50 years, have consistently held that treatment (i.e. dosage and intervals) optimization is obvious.
However, the Pat’458 claims do not recite a sterile vial comprising the pharmaceutical antibody formulation as recited in instant claims 42, 43, 45, 48, 49, 52, 53, and 54. As described previously, Desai teaches that the pharmaceutical antibody formulation is packaged in a sterile glass vial (page 55, line 19-20).
However, the Pat’458 claims do not recite the pharmaceutical antibody formulation wherein the formulation exhibits a dissociation constant (KD) of 1.7-4.2 or about 1.7-4.2 as determined by biolayer interferometry (BLI) when stored at a) 40°C for 7, 14, 21, or 28 days, b) 25°C for 14 days or 1, 3, 6, or 9 months, c) 4°C for 1, 3, 6, 9, 12, or 18 months, or d) -80°C for 1, 3, 6, 9, 12, or 18 months, and/or after being subjected to shear stress or freeze thaws, optionally 3 or 5 freeze thaws as recited in instant claim 88. As described previously, Desai teaches storage conditions of the antibody formulation as well as stability studies that allow refrigeration and freezing of the formulation by using DLS to measure kD. However, Desai does not teach the kD is measured by bio-layer interferometry. As described previously, Domnowski teaches the BLI can be used instead of DLS to allow high throughput performance with minimal preparation. Therefore, it would have been obvious to the person of ordinary skill in the art to substitute DLS with BLI to perform high throughput analysis of antibody with minimal material and sample preparation.
However, Pat’458 claims do not recite the method of treating Alzheimer’s disease, comprising administering the pharmaceutical antibody formulation to a subject in need of Alzheimer’s disease treatment as recited in instant claim 102 and 108.
As described previously, Srejovic teaches that galectin-3 “plays an important role in the pathogenesis of neuroinflammatory and neurogenerative disorders such as multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease” (page 1, abstract). Srejovic further teaches anti-Gal3 antibody that is neuroprotective and decreases pro-inflammatory markers and attenuated microglial activation (page 9, paragraph 1). Finally, Srejovic further discloses that the galectin-3 can be used as a therapeutic target in a variety of pathological conditions as an immunomodulator (page 13, paragraph 1). Therefore, it would have been obvious to the person of ordinary skill in the art to use the pharmaceutical formulation of the antibody as recited in the instant claim to treat Alzheimer’s. One of ordinary skill in the art would have been motivated to use the anti-Gal3 antibody in the Pat’458 claims in the method of treating Alzheimer’s recited in instant claims because galectin 3 is a therapeutic target in Alzheimer’s as taught by Srejovic.
U.S. Copending Applications
Claims 1-2,5,7,9,11,13,15,18,22-23,26-27,29,35,37-39,42-43,45,48-49,52-54,62-64 ,72-73 ,88,102,104,108 and 110-111 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 18, 19, 39, 40, 61, 62 of copending Application No. 17/834,703, filed June 7th, 2022, (herein “App’703”) in view of Desai (cited previously), Srejovic (cited previously), and Domnowski (cited previously).
Regarding instant claims 62, 64, and 72, App’703 claims 18, 40, and 61 recite the heavy chain variable region as a sequence having at least 80% identity to the sequence selected from App’703 SEQ ID NO: 960-968 or 1067-1109. The SEQ ID NO of App’703 has at least 80% identity to the instant SEQ ID NO: 8. For instant claim 73, the SEQ ID NO: 12 is the nucleic acid sequence of SEQ ID NO: 8 when translated as described prior.
Regarding instant claims 63, 64, and 73, App’703 claims 19, 39, and 62 recite the light chain variable region as a sequence having at least 80% identity to the sequence selected from App’703 SEQ ID NO: 974-982 or 1110-1152. The SEQ ID NO of App’703 has at least 80% identity to the instant SEQ ID NO: 9. For instant claim 73, the SEQ ID NO: 13 is the nucleic acid sequence of SEQ ID NO: 9 when translated as described prior.
It is noted that the LCDR1-3 and HCDR1-3 of the instant claim 1, 26, 37, 42, and 102 are not recited in the App’703 but are present in the heavy and light chain variable regions recited above. It is also noted that App’703 claims do not recite the HC, LC sequences as recited in instant claims 68, 69, 76, and 77.
However, App’703 claims do not recite the pharmaceutical formulation of the antibody as recited in instant claims 1, 2, 5, 7, 9, 11, 13, 15, 22, 23, 26, 29, 37, 38, and 102.
As described previously in the nonstatutory double patenting rejection of Pat’638, Desai teaches the pharmaceutical antibody formulation and the excipients. Therefore, it would have been obvious to the person of ordinary skill in the art to formulate the antibody formulation of the anti-Gal3 antibody in the Pat’458 claims with Desai’s teachings to formulate stable antibody formulation for long term storage.
However, App’703 claims do no recite the unit doses of the antibody formulation as recited in instant claim 18, 23, 26, 27, 35, 39, 102, 104, 110, and 111.
As described previously, Desai teaches methods in determining the therapeutically effective dose of the antibody and formulations that allow administration of the antibody. In regards to the specific dosage and interval amounts recited in the instant claims "[w]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955), and see M.P.E.P. § 2144.05 II.A. Moreover, it is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804,809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989). This because, as is made clear from the prior art, the determination of the dosage regimen of a known drug is well within the purview of one of ordinary skill in the art at the time the invention was made, and it would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal intervals of treatment because optimal intervals is an art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art. Therefore, it would be conventional and within the skill of the art to identify the optimal dosages administered and optimal intervals to achieve target levels and therapeutically effective doses. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. It is clear that both the prior art and claimed method perform the same protocol to achieve the same results. It would be conventional and within the skill of the art to determine the optimal treatment regimens. Accordingly, one can see that the courts, over a period of over 50 years, have consistently held that treatment (ie dosage and intervals) optimization is obvious.
However, the App’703 claims do not recite a sterile vial comprising the pharmaceutical antibody formulation as recited in instant claims 42, 43, 45, 48, 49, 52, 53, and 54. As described previously, Desai teaches that the pharmaceutical antibody formulation is packaged in a sterile glass vial (page 55, line 19-20).
However, the App’703 claims do not recite the pharmaceutical antibody formulation wherein the formulation exhibits a dissociation constant (KD) of 1.7-4.2 or about 1.7-4.2 as determined by biolayer interferometry (BLI) when stored at a) 40°C for 7, 14, 21, or 28 days, b) 25°C for 14 days or 1, 3, 6, or 9 months, c) 4°C for 1, 3, 6, 9, 12, or 18 months, or d) -80°C for 1, 3, 6, 9, 12, or 18 months, and/or after being subjected to shear stress or freeze thaws, optionally 3 or 5 freeze thaws as recited in instant claim 88. As described previously, Desai teaches storage conditions of the antibody formulation as well as stability studies that allow refrigeration and freezing of the formulation by using DLS to measure Kd. However, Desai does not teach the Kd is measured by bio-layer interferometry. As described previously, Domnowski teaches the BLI can be used instead of DLS to allow high throughput performance with minimal preparation. Therefore, it would have been obvious to the person of ordinary skill in the art to substitute DLS with BLI to perform high throughput analysis of antibody with minimal material and sample preparation.
However, App’703 claims do not recite the method of treating Alzheimer’s disease, comprising administering the pharmaceutical antibody formulation to a subject in need of Alzheimer’s disease treatment as recited in instant claim 102 and 108.
As described previously, Srejovic teaches that galectin-3 “plays an important role in the pathogenesis of neuroinflammatory and neurogenerative disorders such as multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease” (page 1, abstract). Srejovic further teaches anti-Gal3 antibody that is neuroprotective and decreases pro-inflammatory markers and attenuated microglial activation (page 9, paragraph 1). Finally, Srejovic further discloses that the galectin-3 can be used as a therapeutic target in a variety of pathological conditions as an immunomodulator (page 13, paragraph 1). Therefore, it would have been obvious to the person of ordinary skill in the art to use the pharmaceutical formulation of the antibody as recited in the instant claim to treat Alzheimer’s. One of ordinary skill in the art would have been motivated to use the anti-Gal3 antibody in the App’703 claims in the method of treating Alzheimer’s recited in instant claims because galectin 3 is a therapeutic target in Alzheimer’s as taught by Srejovic.
This is a provisional nonstatutory double patenting rejection.
Claims 1-2,5,7,9,11,13,15,18,22-23,26-27,29,35,37-39,42-43,45,48-49,52-54,62-64,68-69,72-73,76-77,88,102,104,108 and 110-111 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 3, 42, 43, 45, 46, 47, and 48 of copending Application No. 18/578,450, filed on January 11th, 2024, herein “App’450”, in view of Desai (cited previously), and Domnowski (cited previously).
Regarding instant claims 102 and 108, App’450 claim 3 and 42 recite the method of treating an amyloid proteopathy in a subject in need thereof, comprising administering tot the subject an anti-Gal3 antibody or binding fragment wherein the proteopathy is Alzheimer’s disease.
Regarding recited in the instant claim 1, 26, 37, 42, and 102, App’450 claim 43 recites the anti-Gal34 antibody comprises a HCDR1-3 and LCDR1-3 SEQ ID NOs with 100% match to the instant claims (See HCDR1 App’450 SEQ ID NO: 27 to instant SEQ ID NO: 2, HCDR2 App’450 SEQ ID NO: 72 to instant SEQ ID NO: 3, HCDR3 App’450 SEQ ID NO: 113 to instant SEQ ID NO: 4; Compare LCDR1 App’450 SEQ ID NO: 171 to instant SEQ ID NO: 5, LCDR2 App’450 SEQ ID NO: 222 to instant SEQ ID NO: 6, LCDR3 App’450 SEQ ID NO: 249 to instant SEQ ID NO: 7).
Regarding instant claims 62, 64, and 72, App’450 claim 45 recites the heavy chain variable region comprising at least 80% sequence identity to SEQ ID NO: 297-373,803,806-820,940,955-968,1067-1109,1415,1439 (compare to instant SEQ ID NO: 8 and 12).
Regarding instant claims 63, 64, and 73, App’450 claim 46 recites the light chain variable region comprising a sequence having at least 80% identity to the sequence selected from SEQ ID NO: 374-447,821-835,941,943,969-982,1110-1152,1140-1464 (compare to instant SEQ ID NO: 9 and 13).
Regarding instant claim 68 and 76, App’450 claim 47 recites the heavy chain comprising a sequence having at least 80% identity to the sequence selected from SEQ ID NO: 448-494,804,836-850,983-996,1153-1195,1411,1465-1489 (compare to instant SEQ ID NO: 10 and 14).
Regarding instant claims 69 and 77, App’450 claim 48 recites the light chain comprising a sequence having at least 80% identity to the sequence selected from SEQ ID NO: 495-538,805,851-865,997-1010,1196-1238,1412,1490-1514 (compare to SEQ ID NO: 11 and 15).
However, App’450 claims do not recite the pharmaceutical formulation of the antibody as recited in instant claims 1, 2, 5, 7, 9, 11, 13, 15, 22, 23, 26, 29, 37, 38, and 102.
As described previously in the nonstatutory double patenting rejection of Pat’638, Desai teaches the pharmaceutical antibody formulation and the excipients. Therefore, it would have been obvious to the person of ordinary skill in the art to formulate the antibody formulation of the anti-Gal3 antibody in the Pat’458 claims with Desai’s teachings to formulate stable antibody formulation for long term storage.
However, App’450 claims do no recite the unit doses of the antibody formulation as recited in instant claim 18, 23, 26, 27, 35, 39, 102, 104, 110, and 111.
As described previously, Desai teaches methods in determining the therapeutically effective dose of the antibody and formulations that allow administration of the antibody. In regards to the specific dosage and interval amounts recited in the instant claims "[w]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955), and see M.P.E.P. § 2144.05 II.A. Moreover, it is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804,809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989). This because, as is made clear from the prior art, the determination of the dosage regimen of a known drug is well within the purview of one of ordinary skill in the art at the time the invention was made, and it would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal intervals of treatment because optimal intervals is an art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art. Therefore, it would be conventional and within the skill of the art to identify the optimal dosages administered and optimal intervals to achieve target levels and therapeutically effective doses. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. It is clear that both the prior art and claimed method perform the same protocol to achieve the same results. It would be conventional and within the skill of the art to determine the optimal treatment regimens. Accordingly, one can see that the courts, over a period of over 50 years, have consistently held that treatment (ie dosage and intervals) optimization is obvious.
However, the App’450 claims do not recite a sterile vial comprising the pharmaceutical antibody formulation as recited in instant claims 42, 43, 45, 48, 49, 52, 53, and 54. As described previously, Desai teaches that the pharmaceutical antibody formulation is packaged in a sterile glass vial (page 55, line 19-20).
However, the App’450 claims do not recite the pharmaceutical antibody formulation wherein the formulation exhibits a dissociation constant (KD) of 1.7-4.2 or about 1.7-4.2 as determined by biolayer interferometry (BLI) when stored at a) 40°C for 7, 14, 21, or 28 days, b) 25°C for 14 days or 1, 3, 6, or 9 months, c) 4°C for 1, 3, 6, 9, 12, or 18 months, or d) -80°C for 1, 3, 6, 9, 12, or 18 months, and/or after being subjected to shear stress or freeze thaws, optionally 3 or 5 freeze thaws as recited in instant claim 88. As described previously, Desai teaches storage conditions of the antibody formulation as well as stability studies that allow refrigeration and freezing of the formulation by using DLS to measure Kd. However, Desai does not teach the Kd is measured by bio-layer interferometry. As described previously, Domnowski teaches the BLI can be used instead of DLS to allow high throughput performance with minimal preparation. Therefore, it would have been obvious to the person of ordinary skill in the art to substitute DLS with BLI to perform high throughput analysis of antibody with minimal material and sample preparation.
This is a provisional nonstatutory double patenting rejection.
Claims 1-2,5,7,9,11,13,15,18,22-23,26-27,29,35,37-39,42-43,45,48-49,52-54,62-64,68-69,72-73,76-77,88,102,104,108 and 110-111 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 25, 26, 27, 28, 29, 34, 35, 36, 30, 37, 38, 39, 31, 40, 32, and 33 of copending Application No. 18/637,068, filed on April 16, 2024, herein “App’068” in view of Desai (cited previously), Srejovic (cited previously), and Domnowski (cited previously).
Regarding instant claims 1, 26, 37, 42, and 102, App’068 claims 25, 26, 27, 28, and 29 recite HCDR1-3 and LCDR1-3 amino acid sequences of the instant claims 1, 26, 37, 42, and 102.
App’068 claim 34, 35, 36 recite the HCDR1 (SEQ ID NO: 27), HCDR2 (SEQ ID NO: 71), HCDR3 (SEQ ID NO: 112), LCDR1 (SEQ ID NO: 170), LCDR2 (SEQ ID NO: 221), and LCDR3 (SEQ ID NO: 248).
Regarding instant claims 62, 64, and 72, App’068 claims 30 recites the heavy chain variable comprises a sequence having at least 90% identity to SEQ ID NO: 248-296,1848-1864. It is noted that the instant claim requires 80% identity of the sequence. App’068 claim 37 recites the heavy chain variable with the SEQ ID NO: 297 with at least 90% identity. App’068 claim 38 recites the heavy chain variable with the SEQ ID NO: 374 with at least 90% identity. App’068 claim 39 recites the heavy chain variable with the SEQ ID NO: 448 with at least 90% identity.
Regarding instant claims 63, 64, and 73, App’068 claim 31 recites the light chain variable region comprises a sequence having at least 90% identity to SEQ ID NO: 374-447,821-835,941-943,969-982, 1110-1152,1440-1464.1898-1914,1921. It is noted that the instant claim requires 80% identity of the sequence. App’068 claim 40 recites the light chain variable with the SEQ ID NO: 495 with at least 90% identity.
Regarding instant claims 68 and 76, App’068 claim 32 recites the heavy chain comprises a sequence having at least 90% identity to SEQ ID NO: 448-494,804,836-850,983-996,1153-1195,1411,1465-1489,1695-1711. It is noted that the instant claim requires 80% identity of the sequence.
Regarding instant claims 69 and 77, App’068 claim 33 recites the light chain comprises a sequence having at least 90% identity to SEQ ID NO: 495-538,805,851-865,997-1010,1196-1238,1412,1490-1514,1746-1762. It is noted that the instant claim requires 80% identity of the sequence.
However, App’068 claims do not recite the pharmaceutical formulation of the antibody as recited in instant claims 1, 2, 5, 7, 9, 11, 13, 15, 22, 23, 26, 29, 37, 38, and 102.
As described previously in the nonstatutory double patenting rejection of Pat’638, Desai teaches the pharmaceutical antibody formulation and the excipients. Therefore, it would have been obvious to the person of ordinary skill in the art to formulate the antibody formulation of the anti-Gal3 antibody in the Pat’458 claims with Desai’s teachings to formulate stable antibody formulation for long term storage.
However, App’068 claims do no recite the unit doses of the antibody formulation as recited in instant claim 18, 23, 26, 27, 35, 39, 102, 104, 110, and 111.
As described previously, Desai teaches methods in determining the therapeutically effective dose of the antibody and formulations that allow administration of the antibody. In regards to the specific dosage and interval amounts recited in the instant claims "[w]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955), and see M.P.E.P. § 2144.05 II.A. Moreover, it is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804,809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989). This because, as is made clear from the prior art, the determination of the dosage regimen of a known drug is well within the purview of one of ordinary skill in the art at the time the invention was made, and it would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal intervals of treatment because optimal intervals is an art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art. Therefore, it would be conventional and within the skill of the art to identify the optimal dosages administered and optimal intervals to achieve target levels and therapeutically effective doses. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. It is clear that both the prior art and claimed method perform the same protocol to achieve the same results. It would be conventional and within the skill of the art to determine the optimal treatment regimens. Accordingly, one can see that the courts, over a period of over 50 years, have consistently held that treatment (ie dosage and intervals) optimization is obvious.
However, the App’068 claims do not recite a sterile vial comprising the pharmaceutical antibody formulation as recited in instant claims 42, 43, 45, 48, 49, 52, 53, and 54. As described previously, Desai teaches that the pharmaceutical antibody formulation is packaged in a sterile glass vial (page 55, line 19-20).
However, the App’068 claims do not recite the pharmaceutical antibody formulation wherein the formulation exhibits a dissociation constant (KD) of 1.7-4.2 or about 1.7-4.2 as determined by biolayer interferometry (BLI) when stored at a) 40°C for 7, 14, 21, or 28 days, b) 25°C for 14 days or 1, 3, 6, or 9 months, c) 4°C for 1, 3, 6, 9, 12, or 18 months, or d) -80°C for 1, 3, 6, 9, 12, or 18 months, and/or after being subjected to shear stress or freeze thaws, optionally 3 or 5 freeze thaws as recited in instant claim 88. As described previously, Desai teaches storage conditions of the antibody formulation as well as stability studies that allow refrigeration and freezing of the formulation by using DLS to measure Kd. However, Desai does not teach the Kd is measured by bio-layer interferometry. As described previously, Domnowski teaches the BLI can be used instead of DLS to allow high throughput performance with minimal preparation. Therefore, it would have been obvious to the person of ordinary skill in the art to substitute DLS with BLI to perform high throughput analysis of antibody with minimal material and sample preparation.
However, App’068 claims do not recite the method of treating Alzheimer’s disease, comprising administering the pharmaceutical antibody formulation to a subject in need of Alzheimer’s disease treatment as recited in instant claim 102 and 108.
As described previously, Srejovic teaches that galectin-3 “plays an important role in the pathogenesis of neuroinflammatory and neurogenerative disorders such as multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease” (page 1, abstract). Srejovic further teaches anti-Gal3 antibody that is neuroprotective and decreases pro-inflammatory markers and attenuated microglial activation (page 9, paragraph 1). Finally, Srejovic further discloses that the galectin-3 can be used as a therapeutic target in a variety of pathological conditions as an immunomodulator (page 13, paragraph 1). Therefore, it would have been obvious to the person of ordinary skill in the art to use the pharmaceutical formulation of the antibody as recited in the instant claim to treat Alzheimer’s. One of ordinary skill in the art would have been motivated to use the anti-Gal3 antibody in the App’068 claims in the method of treating Alzheimer’s recited in instant claims because galectin 3 is a therapeutic target in Alzheimer’s as taught by Srejovic.
This is a provisional nonstatutory double patenting rejection.
Claims 1-2,5,7,9,11,13,15,18,22-23,26-27,29,35,37-39,42-43,45,48-49,52-54, 88,102,104,108 and 110-111 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 28, 84, 88, 89 of copending Application No. 17/777,573, filed February 18th, 2026 in view of Sun (cited previously), Desai (cited previously), Srejovic (cited previously), and Domnowski (cited previously).
Regarding instant claims 1, 26, 37, 42, and 102, App’573 claim 1 recites a method of disrupting an interaction between galectin 3 and insulin receptor, the method comprising contacting interaction between Gal3 and INSR with an anti-Gal3 antibody wherein the anti-Gal3 antibody comprises a light chain variable region comprising a LCDR1-3 and heavy chain variable region comprising HCDR1-3 (App’573 claim 1, page 3, see figure 21 of this office action)
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Figure 21. App'573 claim 1, page 3
Regarding instant claims 1, 26, 37, 42, and 102, App’573 claim 1 recite HCDR1 SEQ ID NO: 30, HCDR2 SEQ ID NO: 51, HCDR3 SEQ ID NO: 75 which corresponds to the instant SEQ ID NO: 2, 3, and 4, of instant claims 1, 26, 37, 42, and 102.
Regarding instant claims 1, 26, 37, 42, and 102, App’573 claim 1 recite LCDR1 SEQ ID NO: 103, LCDR2 SEQ ID NO: 130, LCDR3 SEQ ID NO: 146 which corresponds to the instant SEQ ID NO: 5, 6, and 7, of instant claims 1, 26, 37, 42, and 102.
Regarding instant claims 1, 26, 37, 42, and 102, App’573 claim 28 recites a method in treating diabetes mellitus in a subject comprising administering the anti-Gal3 antibody to the subject wherein the antibody comprises the SEQ ID NOs of instant claims 1, 26, 37, 42, and 102 (HCDR1 SEQ ID NO: 30, HCDR2 SEQ ID NO: 51, HCDR3 SEQ ID NO: 75 and LCDR1 SEQ ID NO: 103, LCDR2 SEQ ID NO: 130, LCDR3 SEQ ID NO: 146) that correspond to the HCDR1-3 and LCDR1-3 of the instant claims 1, 26, 37, 42, and 102 (page 7 of App’573 claims).
Regarding instant claims 1, 26, 37, 42, and 102, App’573 claim 84 is withdrawn – currently amended also recites the anti-Gal3 antibody with the HCDR1-3 and LCDR1-3 SEQ ID NOs (page 11 of App’573 claims, “HCDR1 SEQ ID NO: 30, HCDR2 SEQ ID NO: 51, HCDR3 SEQ ID NO: 75 and LCDR1 SEQ ID NO: 103, LCDR2 SEQ ID NO: 130, LCDR3 SEQ ID NO: 146”).
It is noted that Pat’458 claims do not teach the VH, VL, HC, LC sequences as recited in instant claims 62, 63, 64, 68, 69, 72, 73, 76, and 77. Sun teaches the VH, VL, HC, LC amino acid and nucleic acid sequences as described prior (see rejections under 35 U.S.C. 103). Sun further teaches that the antibody induces immune activation or promotes T cell or Natural Killer Cell proliferation and can treat immune related disease in a subject (page 1, abstract and page 74 column 7, lines 4-6, “methods of inducing immune activation or promoting T cell or Natural Killer cell proliferation with an antibody that specifically binds to Gal3.”). Therefore, it would have been obvious to the person of ordinary skill in the art to use the sequences as taught by Sun to treat immune related diseases that express Galectin 3 with the anti-Gal3 antibody and expect reasonable expectation of success.
Regarding instant claims 1, 2, 5, 7, 9, 11, 13, 15, 22, 23, 26, 29, 37, 38, and 102, App’573 claim 88 and 89 are withdrawn – currently amended and recite the pharmaceutical formulation comprising the anti-Gal3 antibody but does not recite the specific excipients of the pharmaceutical antibody formulation of the claimed invention.
As described previously in the nonstatutory double patenting rejection of Pat’638, Desai teaches the pharmaceutical antibody formulation and the excipients. Therefore, it would have been obvious to the person of ordinary skill in the art to formulate the antibody formulation of the anti-Gal3 antibody in the App’573 claims with Desai’s teachings to formulate stable antibody formulation for long term storage.
However, App’573 claims do no recite the unit doses of the antibody formulation as recited in instant claim 18, 23, 26, 27, 35, 39, 102, 104, 110, and 111.
As described previously, Desai teaches methods in determining the therapeutically effective dose of the antibody and formulations that allow administration of the antibody. In regards to the specific dosage and interval amounts recited in the instant claims "[w]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955), and see M.P.E.P. § 2144.05 II.A. Moreover, it is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804,809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989). This because, as is made clear from the prior art, the determination of the dosage regimen of a known drug is well within the purview of one of ordinary skill in the art at the time the invention was made, and it would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal intervals of treatment because optimal intervals is an art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art. Therefore, it would be conventional and within the skill of the art to identify the optimal dosages administered and optimal intervals to achieve target levels and therapeutically effective doses. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. It is clear that both the prior art and claimed method perform the same protocol to achieve the same results. It would be conventional and within the skill of the art to determine the optimal treatment regimens. Accordingly, one can see that the courts, over a period of over 50 years, have consistently held that treatment (ie dosage and intervals) optimization is obvious.
However, the App’573 claims do not recite a sterile vial comprising the pharmaceutical antibody formulation as recited in instant claims 42, 43, 45, 48, 49, 52, 53, and 54. As described previously, Desai teaches that the pharmaceutical antibody formulation is packaged in a sterile glass vial (page 55, line 19-20).
However, the App’573 claims do not recite the pharmaceutical antibody formulation wherein the formulation exhibits a dissociation constant (KD) of 1.7-4.2 or about 1.7-4.2 as determined by biolayer interferometry (BLI) when stored at a) 40°C for 7, 14, 21, or 28 days, b) 25°C for 14 days or 1, 3, 6, or 9 months, c) 4°C for 1, 3, 6, 9, 12, or 18 months, or d) -80°C for 1, 3, 6, 9, 12, or 18 months, and/or after being subjected to shear stress or freeze thaws, optionally 3 or 5 freeze thaws as recited in instant claim 88. As described previously, Desai teaches storage conditions of the antibody formulation as well as stability studies that allow refrigeration and freezing of the formulation by using DLS to measure Kd. However, Desai does not teach the Kd is measured by bio-layer interferometry. As described previously, Domnowski teaches the BLI can be used instead of DLS to allow high throughput performance with minimal preparation. Therefore, it would have been obvious to the person of ordinary skill in the art to substitute DLS with BLI to perform high throughput analysis of antibody with minimal material and sample preparation.
However, App’573 claims do not recite the method of treating Alzheimer’s disease, comprising administering the pharmaceutical antibody formulation to a subject in need of Alzheimer’s disease treatment as recited in instant claim 102 and 108.
As described previously, Srejovic teaches that galectin-3 “plays an important role in the pathogenesis of neuroinflammatory and neurogenerative disorders such as multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease” (page 1, abstract). Srejovic further teaches anti-Gal3 antibody that is neuroprotective and decreases pro-inflammatory markers and attenuated microglial activation (page 9, paragraph 1). Finally, Srejovic further discloses that the galectin-3 can be used as a therapeutic target in a variety of pathological conditions as an immunomodulator (page 13, paragraph 1). Therefore, it would have been obvious to the person of ordinary skill in the art to use the pharmaceutical formulation of the antibody as recited in the instant claim to treat Alzheimer’s. One of ordinary skill in the art would have been motivated to use the anti-Gal3 antibody in the App’573 claims in the method of treating Alzheimer’s recited in instant claims because galectin 3 is a therapeutic target in Alzheimer’s as taught by Srejovic.
This is a provisional nonstatutory double patenting rejection.
Claims 1-2,5,7,9,11,13,15,18,22-23,26-27,29,35,37-39,42-43,45,48-49,52-54,62-64,68-69,72-73,76-77,88,102,104,108 and 110-111 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6, 7, 9, 8, 10, 12, 13, 14, 15, 16, 18, 19, 20, 21, and 22 of copending Application No. 19/382,093, filed April 24th, 2026 (herein “App’093”) in view of Desai (cited previously), Srejovic (cited previously), and Domnowski (cited previously).
Regarding instant claims 1, 26, 37, 42, and 102, App’093 claim 6 recites the method of inducing immune activation, comprising contacting cells expressing Gal3 and TIM-3 with an anti-Gal3 antibody. The antibody recited in App’093 claim 6 recites:
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, which corresponds to the LCDR1-3 and HCDR1-3 of the instant claims 1, 26, 37, 42, and 102.
App’093 claim 12 recites the same SEQ ID NOs of the LCDR1-3 and HCDR1-3 but for the method of promoting T cell or NK cell proliferation.
App’093 claim 18 recites the same SEQ ID NOs of the LCDR1-3 and HCDR1-3 but for the method of treating cancer.
Regarding instant claims 62, 63, 64, 72, and 73, App’093 claim 7 and 9 recites the heavy chain variable region (VH) comprising the SEQ ID NO: 230 and light chain variable region (VL) comprising the SEQ ID NO: 258 and having at least 90% identity.
Regarding instant claims 68, 69, 76, and 77, App’093 claim 8 and 10 recite the heavy chain comprising the SEQ ID NO: 265 and light chain comprising the SEQ ID NO: 266 and having at least 90% identity.
App’093 claims 13, 14, 15, and 16 recite the same antibody VH and VL as well as heavy chain and light chain sequences as described above.
App’093 claims 19, 20, 21, and 22 recite the same antibody VH and VL as well as heavy chain and light chain sequences as described above.
However, App’093 claims do not recite the pharmaceutical formulation of the antibody as recited in instant claims 1, 2, 5, 7, 9, 11, 13, 15, 22, 23, 26, 29, 37, 38, and 102.
As described previously in the nonstatutory double patenting rejection of Pat’638, Desai teaches the pharmaceutical antibody formulation and the excipients. Therefore, it would have been obvious to the person of ordinary skill in the art to formulate the antibody formulation of the anti-Gal3 antibody in the App’093 claims with Desai’s teachings to formulate stable antibody formulation for long term storage.
However, App’093 claims do no recite the unit doses of the antibody formulation as recited in instant claim 18, 23, 26, 27, 35, 39, 102, 104, 110, and 111.
As described previously, Desai teaches methods in determining the therapeutically effective dose of the antibody and formulations that allow administration of the antibody. In regards to the specific dosage and interval amounts recited in the instant claims "[w]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955), and see M.P.E.P. § 2144.05 II.A. Moreover, it is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804,809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989). This because, as is made clear from the prior art, the determination of the dosage regimen of a known drug is well within the purview of one of ordinary skill in the art at the time the invention was made, and it would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal intervals of treatment because optimal intervals is an art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art. Therefore, it would be conventional and within the skill of the art to identify the optimal dosages administered and optimal intervals to achieve target levels and therapeutically effective doses. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. It is clear that both the prior art and claimed method perform the same protocol to achieve the same results. It would be conventional and within the skill of the art to determine the optimal treatment regimens. Accordingly, one can see that the courts, over a period of over 50 years, have consistently held that treatment (ie dosage and intervals) optimization is obvious.
However, the App’093 claims do not recite a sterile vial comprising the pharmaceutical antibody formulation as recited in instant claims 42, 43, 45, 48, 49, 52, 53, and 54. As described previously, Desai teaches that the pharmaceutical antibody formulation is packaged in a sterile glass vial (page 55, line 19-20).
However, the App’093 claims do not recite the pharmaceutical antibody formulation wherein the formulation exhibits a dissociation constant (KD) of 1.7-4.2 or about 1.7-4.2 as determined by biolayer interferometry (BLI) when stored at a) 40°C for 7, 14, 21, or 28 days, b) 25°C for 14 days or 1, 3, 6, or 9 months, c) 4°C for 1, 3, 6, 9, 12, or 18 months, or d) -80°C for 1, 3, 6, 9, 12, or 18 months, and/or after being subjected to shear stress or freeze thaws, optionally 3 or 5 freeze thaws as recited in instant claim 88. As described previously, Desai teaches storage conditions of the antibody formulation as well as stability studies that allow refrigeration and freezing of the formulation by using DLS to measure Kd. However, Desai does not teach the Kd is measured by bio-layer interferometry. As described previously, Domnowski teaches the BLI can be used instead of DLS to allow high throughput performance with minimal preparation. Therefore, it would have been obvious to the person of ordinary skill in the art to substitute DLS with BLI to perform high throughput analysis of antibody with minimal material and sample preparation.
However, App’093 claims do not recite the method of treating Alzheimer’s disease, comprising administering the pharmaceutical antibody formulation to a subject in need of Alzheimer’s disease treatment as recited in instant claim 102 and 108.
As described previously, Srejovic teaches that galectin-3 “plays an important role in the pathogenesis of neuroinflammatory and neurogenerative disorders such as multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease” (page 1, abstract). Srejovic further teaches anti-Gal3 antibody that is neuroprotective and decreases pro-inflammatory markers and attenuated microglial activation (page 9, paragraph 1). Finally, Srejovic further discloses that the galectin-3 can be used as a therapeutic target in a variety of pathological conditions as an immunomodulator (page 13, paragraph 1). Therefore, it would have been obvious to the person of ordinary skill in the art to use the pharmaceutical formulation of the antibody as recited in the instant claim to treat Alzheimer’s. One of ordinary skill in the art would have been motivated to use the anti-Gal3 antibody in the App’093 claims in the method of treating Alzheimer’s recited in instant claims because galectin 3 is a therapeutic target in Alzheimer’s as taught by Srejovic.
This is a provisional nonstatutory double patenting rejection.
Claims 1-2,5,7,9,11,13,15,18,22-23,26-27,29,35,37-39,42-43,45,48-49,52-54,62-64, 69, 72-73, 77,88,102,104,108 and 110-111 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 51, 52, 53, 55, 69, 60, 62, 63, 64, 65, 66, 67, 68, 69, 70, of copending Application No. 19/116,297 filed March 27th, 2025 (herein “App’297”) in view of Desai (cited previously) and Domnowski (cited previously).
Regarding instant claims 1, 26, 37, 42, and 102, App’297 claim 51, 69, 70 recite the method of treating neurodegenerative disease comprising administering the anti-Gal3 antibody that has the HCDR1-3 and LCDR1-3 sequences:
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Regarding instant claims 102 and 108, App’297 claim 52 and 53 recite the method of treating a disease is Alzheimer’s disease with the anti-Gal3 antibody.
Regarding instant claims instant claim 18, 23, 26, 27, 35, 39, 102, 104, 110, and 111, App’297 claims 59, 60, and 64 recite the anti-Gal3 antibody and therapeutic formulation is administered at least 1-12 times a month or at least a month via intravenous infusion for a total administered dose of 140-4000 mg or 0.1-300 mg/kg. App’297 claim 55 recites the anti-Gal3 antibody is administered at a dose of at least 70 mg or at least 0.1 mg/kg. In regards to the specific dosage and interval amounts recited in the instant claims "[w]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955), and see M.P.E.P. § 2144.05 II.A. Moreover, it is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804,809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989). This because, as is made clear from the prior art, the determination of the dosage regimen of a known drug is well within the purview of one of ordinary skill in the art at the time the invention was made, and it would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal intervals of treatment because optimal intervals is an art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art. Therefore, it would be conventional and within the skill of the art to identify the optimal dosages administered and optimal intervals to achieve target levels and therapeutically effective doses. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. It is clear that both the prior art and claimed method perform the same protocol to achieve the same results. It would be conventional and within the skill of the art to determine the optimal treatment regimens. Accordingly, one can see that the courts, over a period of over 50 years, have consistently held that treatment (i.e. dosage and intervals) optimization is obvious.
Regarding instant claims 1, 2, 5, 7, 9, 11, 13, 15, 22, 23, 26, 29, 37, 38, and 102, App’297 claim 62, 63, 65, and 70 recite the anti-Gal3 antibody is administered as a therapeutic formulation comprising 20 mg/ml of antibody, 20 mM L-histidine, 5 mM Methionine, 100 mM NaCl, 0.02% polysorbate-80 and a pH of 5.8.
Regarding instant claims 62, 64, and 72, App’297 claim 66 recite the anti-Gal3 antibody comprises a heavy chain variable region of SEQ ID NO: 298, or 309-311. It is noted that the instant claim requires 80% identity of the sequence.
Regarding instant claims 63, 64, and 73, App’297 claim 67 recite the anti-Gal3 antibody comprises a light chain variable region of SEQ ID NO: 375, 387, or 388. It is noted that the instant claim requires 80% identity of the sequence.
Regarding instant claims 69 and 77, App’297 claim 68 recite the anti-Gal3 antibody comprises a light chain of SEQ ID NO: 496 or 508-510. It is noted that the instant claim requires 80% identity of the sequence. It is noted that App’297 claims do not recite the anti-Gal3 antibody with a heavy chain sequence as recited in instant claims 68 and 76.
However, the App’297 claims do not recite a sterile vial comprising the pharmaceutical antibody formulation as recited in instant claims 42, 43, 45, 48, 49, 52, 53, and 54. As described previously in the nonstatutory double patenting rejection of Pat’638, Desai teaches the pharmaceutical antibody formulation and the excipients and teaches that the antibody formulation is stable and can be stored for long term. Therefore, it would have been obvious to the person of ordinary skill in the art to formulate the antibody formulation of the anti-Gal3 antibody in the Pat’166 claims with Desai’s teachings to formulate stable antibody formulation for long term storage. As described previously, Desai teaches that the pharmaceutical antibody formulation is packaged in a sterile glass vial (page 55, line 19-20).
However, the App’297 claims do not recite the pharmaceutical antibody formulation wherein the formulation exhibits a dissociation constant (KD) of 1.7-4.2 or about 1.7-4.2 as determined by biolayer interferometry (BLI) when stored at a) 40°C for 7, 14, 21, or 28 days, b) 25°C for 14 days or 1, 3, 6, or 9 months, c) 4°C for 1, 3, 6, 9, 12, or 18 months, or d) -80°C for 1, 3, 6, 9, 12, or 18 months, and/or after being subjected to shear stress or freeze thaws, optionally 3 or 5 freeze thaws as recited in instant claim 88. As described previously, Desai teaches storage conditions of the antibody formulation as well as stability studies that allow refrigeration and freezing of the formulation by using DLS to measure Kd. However, Desai does not teach the Kd is measured by bio-layer interferometry. As described previously, Domnowski teaches the BLI can be used instead of DLS to allow high throughput performance with minimal preparation. Therefore, it would have been obvious to the person of ordinary skill in the art to substitute DLS with BLI to perform high throughput analysis of antibody with minimal material and sample preparation.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No Claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Lam Thuy Vi Tran Ho whose telephone number is (571)272-9135. The examiner can normally be reached Monday-Friday 7:30-3.
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/LAM THUY VI TRAN HO/Examiner, Art Unit 1647 /L.T./Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
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