DETAILED ACTION
1. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 5/19/2025 has been entered.
2. Claims 18-21, 23-27, 29, 30 and 32-35 are pending under examination as they read on a method of inhibiting galectin-10 crystal formation with anti-Galectin 10 antibody and the species 1) an epitope comprising Ser2, Leu3, Leu4, Pro5, Pro7, Tyr8, Thr9, Glu10, Ala11, Lys23, Arg25, Met44, Gly86, Gln87, Glu88, Phe89, Glu90, Asn105, Met123, Gln125, Thr133, Lys134, and Phe135 (ii) an antibody or antigen binding fragment thereof comprising a HCDR3, HCDR2, HCDR1, LCDR3, LCDR2, and LCDR1 corresponding to SEQ ID NOs: 162, 161, 160, 179, 178, and 177, respectively, and (iii) asthma.
3. Applicant’s IDS, filed 5/19/2025, is acknowledged.
4. The following is a quotation of 35 U.S.C. 112(a) (Pre-AIA 35 U.S.C. 112, first paragraph):
(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.
5. Claims 18-21 and 23-27 stand rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), as containing subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a New Matter rejection.
The amino acid “Met123” claimed in claims 18, 20, 23, 25, represents a departure from the specification and the claims as originally filed for the same reasons set forth in the previous Office Action mailed 02/19/2025.
Applicant’s arguments, filed 05/18/2025, have been fully considered, but have not been found convincing.
Applicant submits for support for “Met123” can be found in Tables 26 and 27 at pp. 104-105 of the instant specification. Specifically, these Tables show that antibody clone 7B7 makes contact with amino acid residue 123 of galectin-10. As shown by the sequence of SEQ ID NO: 141 at page 20 of the instant specification, the amino acid at position 123 of galectin-10 is methionine.
This is not found persuasive because clone 7B07 binds a specific conformational epitope comprising a single species of the following residues 4, 5, 7-11, 44, 123, 125 and 135. However, claims 18, 20, 23, 25 claims a genus of antibodies that bind only Met123 and a genus of antibodies that bind the Met123 in context with Ser2, Leu3, Leu4, . . . and/or Phe135. The specification does not contemplate antibodies that binds only Met123 or combination of Met123 in context with other resides recited in the claims.
PNG
media_image1.png
146
866
media_image1.png
Greyscale
PNG
media_image2.png
308
866
media_image2.png
Greyscale
A subgenus is not necessarily implicitly described by a genus encompassing it and a species upon which it reads, see In re Smith, 458 F.2d 1389, 1395, 173 USPQ 679, 683 (CCPA 1972).
Further, Novozymes A/S v. DuPont Nutrition Biosciences (Fed. Cir. 2013), the claimed invention is considered "as an integrated whole" rather than merely element by element. The instant specification does not particularly identify this particular combination of limitations.
6. Claims 18-21, 23-27, 29-30 and 32-34 stand rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention for the same reasons set forth in the previous Office Action mailed 10/07/2024 and 02/19/2025.
Applicant’s arguments, filed 05/19/2025, have been fully considered, but have not been found convincing.
Applicant submits in conjunction with statements from case laws and MPEP that the instant claims are not directed to a genus of antibodies. Rather, the instant claims are based on Applicant’s discovery that anti-galectin-10 antibodies bind to galectin-10, block Charcot-Leydon crystal (CLC) formation, solubilize pre-existing CLCs, and neutralize the effects of CLCs in vivo. CLCs are extracellular protein crystals that are formed by galectin-10 proteins and are associated with inflammatory diseases (e.g., asthma) and some cancers (e.g., AML). Applicants found that CLCs did not form when anti-galectin-10 monoclonal antibodies or scFvs were included in the CLC formation experiment, whereas there was 100% CLC formation in the samples that included control scFvs or IgGs (Example 9). The instant specification also demonstrates that an anti-galectin-10 antibody can solubilize already existing CLCs in vitro” and ex vivo (Example 13) in the environment of human mucus. Further, Applicants found that transferring CLCs to humanized mice caused bronchoconstriction and that administering an anti-galectin-10 antibody to the mice completely neutralized the bronchoconstriction. (see Example 14). These results demonstrate that anti- galectin-10 antibodies can reduce the amount of CLCs both in vitro and in vivo and that an anti-galectin-10 antibody could be used to treat diseases associated with CLCs.
Applicant further submits that the instant application also provides numerous explicit examples of anti-galectin-10 scFvs, monoclonal antibodies, Fab fragments, and VHHs (examples 8,15, 17, 19). The Examiner alleges that “the specification does not disclose a recognized correlation between the structure of the galectin-10 protein of SEQ ID NO: 141 and the protein’s claimed function, treating each and every disease associated with the presence or formation of galectin-10 crystals. Applicants traverse. Through epitope mapping and crystal structure experiments, Applicants have clearly demonstrated that the epitopes of galectin-10 that these antibodies bind to include the amino acids recited in claims 18 and 23. These epitopes form a crystal packing interface surface patch on galectin-10 that contacts one or more neighboring galectin-10 molecules in the crystalline lattice. The disclosed antibodies bind to many of these epitopes. Moreover, the numerous described antibodies were shown to cross-compete in a tandem assay, as claimed in claims 19, 24, 29, and 32, indicating that they bind to the same epitope on galectin-10-His.
Applicants submit that the extensive teachings in the instant specification regarding the claimed methods of inhibiting galectin-10 crystal formation and reducing the amount of galectin-10 crystals in a subject are more than sufficient to satisfy the written description requirement. The specification provides evidence that the anti-galectin-10 antibodies described therein block the formation of new CLCs and solubilize existing CLCs and that this translates to effectively blocking the effects of CLCs in vivo. The specification further discloses the epitopes that the anti-galectin-10 antibodies bind to and methods of making such antibodies. Thus, based on the disclosure of the instant application, the skilled artisan would understand that Applicants were in possession of the claimed invention at the time of filing. Applicant concluded that the requirement of 35 U.S.C. § 112(a) for written description has been satisfied.
This is not found persuasive because human galectin-10 is 142 amino acids in length. It is well known in the art that the epitope binding site of an antibody is usually defined by no more than six to eight amino acids. Neither the instant specification nor the art of record shows that the majority of antibodies that bind to any one of the multitude of epitopes present in a protein having the sequence of Gal-10 are capable of treating any disease or condition associated with the presence of formation of galectin-10 crystals, as is required for the operability of the claimed product. The required genus is not adequately described because neither the specification nor the art of record describes a representative number of species of antibody within the required genus.
For example, Persson et al. Protein crystallization promotes type 2 immunity and is reversible by antibody treatment. Science 364, 751, May 2019, teaches the epicenter of each crystal-dissolving antibody-binding epitope on Gal10 was situated at Tyr69, a residue we had identified as a critical crystal-packing hotspot. These antibodies rapidly dissolved preexisting CLCs in vitro and in the native mucus environment of patients. Crystal-dissolving antibodies suppressed airway inflammation, goblet-cell metaplasia, bronchial hyperreactivity, and IgE synthesis induced by CLC and house dust mite inhalation in a humanized mouse model.
Artisans are well aware that knowledge of a given antigen (for instance human galectin-10) provides no information concerning the sequence/structure of antibodies that bind the given antigen. For example, Edwards et al (J Mol Biol. 2003 Nov 14;334(1): 103-18) teach that over 1,000 different antibodies to a single protein can be generated, all with different sequences spanning almost the entire heavy and light chain germline repertoire (42/49 functional heavy chain germlines and 33 of 70 V-lambda and V-kappa light chain germlines, and with extensive diversity in the FICDR3 region sequences (that are generated by VDJ germline segment recombination) as well, see entire document). Similarly, Lloyd et al (Protein Eng Des Sel. 2009 Mar;22(3):159-68) teach that a large majority of VH/VL germline gene segments are used in the antibody response to an antigen, even when the antibodies were selected by antigen binding, as their sequencing studies revealed that out of 841 unselected and 5,044 selected antibodies, all but one of the 49 functional VH gene segments was observed (see entire document). Goel et al (J Immunol. 2004 Dec 15; 173(12):7358-67) disclose the synthesis of three mAbs that bind to the same short (12-mer) peptide and found that the sequences of these antibodies which bound the same epitope exhibited diverse V gene usage indicating their independent germline origin (see entire document). As such, it does not seem possible to predict the sequence/structure of an antibody that binds a given antigen as there does not appear to be any common or core structure present within all antibodies that gives rise to the function of antigen binding. Further, given data such as that of Edwards et al. indicating the diversity of sequence bound in a population of antibodies that bind to a given antigen no number of species appears to reasonably representative of the breadth of the genus of antibodies that bind the given antigen. Indeed, Kanyavuz et al (Nat Rev Immunol. 2019 Jun; 19(6):355-368) teach that “Theoretically, under physiological conditions, the human immune system can generate BCRs with 1026 distinct sequences, an astronomical number that is far greater than the calculated number of all B cell clones that can be generated during the lifespan of a healthy human (estimated to be 4 x 1014).
Importantly, the USPTO has released a Memo on the Clarification of Written Description Guidance For Claims Drawn to Antibodies and Status of 2008 Training Materials, 02/22/2018.
See https://www.uspto.gov/sites/default/files/documents/amgen_22feb2018.pdf.
The Memo clarifies the applicability of USPTO guidance regarding the written description requirement of 35 U.S.C. § 112(a) concerning the written description requirement for claims drawn to antibodies, including the following.
“In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional”.
In contrast to applicant’s reliance of describe the epitope of the galectin-10 in providing a fully characterized antigen / specific epitope as well as claiming structural elements of the antigen, one or more functions recited in the claims and binding affinity, there is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of the claimed anti-galectin-10 antibodies to demonstrate possession. Also, see Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017).
There is no evidence that knowledge of the chemical structure of an antigen gives the required kind of structure identifying information about the corresponding antibodies Applicants attempt to describe the invention by describing something that is not the invention: viz., the antigens to which the antibodies may bind. There nothing in the disclosure that describes the antibodies as required by the test set forth in Ariad.
However, the anti-galectin-10 antibodies are required to practice the invention. The specification fails to provide any specific structural or physical information so as to define a genus of antibodies having the desired therapeutic properties. Applicant is merely relying on the identification of galectin-10 as the antigen and the well-known structure of antibodies in general. However, the claims do not recite a general antibody, but an antibody having a specific desired activity. However, Federal Circuit clarification of the law of written description as it applies to antibodies. Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017).
The claims are directed to a genus of anti-galectin-10 antibodies. However, Federal Circuit clarification of the law of written description as it applies to antibodies. The U.S. Court of Appeals for the Federal Circuit (Federal Circuit) decided Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017), which concerned adequate written description for claims drawn to antibodies. The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. § 112(a) requires adequate written description of the antibody itself. Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called "newly characterized antigen" test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. § 112(a) for a claim drawn to an antibody. Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the court also stressed that the "newly characterized antigen" test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872 F.3d at 1378-79, quoting Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1345 (Fed. Cir. 2010). In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional.
Moreover, there is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of the claimed anti-Galectin-10 antibodies to demonstrate possession. Also, see Amgen Inc. v. Sanofi, Aventisub LLC, No. 2017-1480 (Fed. Cir. 2017). The Court reiterated that adequate written description must “contain enough information about the actual makeup of the claimed products . . . .” The Court simultaneously suggested that the “newly characterized antigen” test “flouts” section 112 because it “allows patentees to claim antibodies by describing something that is not the invention, i.e. the antigen.” The Court concluded that for written description of an antibody to be adequate when presented with “functional” terminology, there must be an established correlation in the art between structure and function.
Further, the claims encompass a genus of anti-Gal-10 antibodies that binds to non-contiguous conformational epitopes.
Table 27 of the specification shows that each antibody has different constant with residues of the galectin-10 dimer in the crystal structure.
There is no disclosure in the specification of antibody structures or other information necessary to obtain the functional result of binding to a conformational epitope within Ser2, Leu3, Leu4, Pro5, Pro7, Tyr8, Thr9, Glu10, Ala11, Lys23, Arg25, Met44, Gly86, Gln87, Glu88, Phe89, Glu90, Asn105, Met123, Gln125, Thr133, Lys134, and/or Phe135 of SEQ ID NO:141, and cross-reacting antibodies . Moreover, there is no disclosure in the specification of what antibody structures obtain the functional results of inhibiting galectin-10 crystal formation in a subject having asthma. Consequently , the instant “ claims merely recite a description of the problem to be solved while claiming all solutions to it and . . . cover any antibodies later actually invented and determined to fall within the claim’s functional boundaries leaving it to the pharmaceutical industry to complete an unfinished invention.” Ariad Pharmaceuticals, Inc. V. Eli Lilly and Co., 598 F.3d 1336, 1353 (Fed. Cir. 2010).
However, the specification does not provide adequate written description of a sufficient representative number of antibodies falling within the scope of the genus and has not described the antibody structural features common or shared among the antibodies having the claimed binding function sufficient to describe the entire genus of antibodies meeting the claims. Regarding the lack of structure/function description, a disclosure of 10 antibodies do not predict the entire claimed genus of any and all other anti-galectin-10 antibodies that binds within the non-contiguous conformational epitope of Ser2, Leu3, Leu4, Pro5, Pro7, Tyr8, Thr9, Glu10, Ala11, Lys23, Arg25, Met44, Gly86, Gln87, Glu88, Phe89, Glu90, Asn105, Met123, Gln125, Thr133, Lys134, and/or Phe135 of SEQ ID NO:141, yet to be discovered that function as claimed.
Claims require the anti-Galectin-10 antibody “cross competes for binding to human galectin-10 ” with known anti-Gal-10 antibody recited in claims 19, 24, 29 and 32. While the amino acid sequence of Galectin-10 was known, immunizing an animal with Galectin-10 will generate antibodies directed to a number of different epitopes within the non-contiguous conformational epitope of Ser2, Leu3, Leu4, Pro5, Pro7, Tyr8, Thr9, Glu10, Ala11, Lys23, Arg25, Met44, Gly86, Gln87, Glu88, Phe89, Glu90, Asn105, Met123, Gln125, Thr133, Lys134, and/or Phe135 of SEQ ID NO:141and not necessarily to the same epitope which is bound by the claimed antibody recited in claims 19, 24, 29, 32. The knowledge of the amino acid sequence of Galectin-10, by itself, did not put Applicants in possession of antibodies that competes with epitope as the epitope bound by the claimed anti-Galectin-10 antibodies.
This case is similar to Centocor Ortho Biotech, Inc. v. Abbott Laboratories, 636 F.3d 1341 (Fed. Cir. 2011). In Centocor, patentee claimed an antibody or antibody fragment that competitively inhibits binding of A2 (a mouse antibody) and that binds an epitope of TNF-α with a specified affinity. 636 F.3d at 1346. Both TNF-α protein and antibodies to that protein were known in the literature. Id. at 1352. Patentee argued that the patent at issue satisfied the written description for the claimed antibodies because it "not only describes the antibodies by their binding affinity for TNF-α, but further describes the antibodies by specifying that they competitively inhibit binding of the A2 mouse antibody to TNF-α." Id. At 1349. The Federal Circuit rejected this argument, finding that "[a]t bottom, the asserted claims constitute a wish list of properties that a fully-human, therapeutic TNF-α antibody should have: high affinity, neutralizing activity, and the ability to bind in the same place as the mouse A2 antibody." Id. At 1351. The court explained that "[t]he specification at best describes a plan for making fully-human antibodies and then identifying those that satisfy the claim limitations."
In finding that the specification at issue did not provide written description support for the claimed antibodies, the Centocor court recognized that the written description does not require examples or an actual reduction to practice, but clarified that "it does demand ... that one of skill in the art can 'visualize or recognize' the claimed antibodies based on the specification's disclosure." Id. at 1353. "In other words the specification must demonstrate constructive possession." Id; see also, AbbVie Deutschland GmbH & Co., KG., v. Janssen Biotech, Inc., 759 F.3d 1285, 1301 (Fed. Cir. 2014) (reiterating requirement for structure-function correlation in functionally defined claims and finding that the patents at issue do not meet the written description requirement because they "do not describe any common structural features of the claimed antibodies.").
Here, as in Centocor, Applicant seeks to ground written description support for a claimed antibody in its competitive inhibition of another antibody (here, scFv 7B07, in Centocor, mouse A2 antibody) and in the description of a known antigen (here Galectin-10, in Centocor, TNF-α). While the state of the art has progressed since the Federal Circuit's decision in Centocor, the basic problem remains that the description at issue must allow one of skill in the art to "visualize or recognize" the claimed antibodies. Here, the evidence of record does not support that the skilled artisan would have visualized or recognized the claimed antibodies based on the description provided. As in Centocor, the Specification provides only a plan for identifying the claimed antibodies.
Possession is not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. Sufficient description to show possession of such a genus may be achieved by means of a recitation of anti-Galectin competing antibodies falling within the scope of the genus or of a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. See Eli Lilly, 119F.3d at 1568, 43 USPQ2d at 1406.
While the claims here are directed to methods of using antibodies, rather than the antibodies themselves, but the same standard applies with regard to the written description requirement. See University of Rochester v. G.D. Searle & Co., 358 F.3d 916,926 (Fed. Cir. 2004):
Regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to that subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.
In University of Rochester, the "claimed method depend[ed] upon finding a compound that selectively inhibits PGHS-2 activity. Without such a compound, it is impossible to practice the claimed method of treatment." Id. ( citation omitted). Similarly here, the claimed methods cannot be practiced without antibodies having the inhibiting galectin-10 crystal formation activity recited in the claims. Applicant’s argument that the claims are adequately described because they are directed to a method, not a composition of matter, is therefore unpersuasive.
7. Claims 18-21, 23-27, 29-30 and 32-34 stand rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating asthma with the specific anti-galectin-10 antibodies having the CDRs sequences of 1D11, 6F5, 4E8, 1C9 3A03, 1A12, 2E12, 4G05, 2C02, 4B10, 6A11, 4H10, 6F11, 2B11, 2E12, 6A05, 6A05, 6A08, 2F09, 6F06, 6B06, 6E10, 7B7, 8H11, 10A06, 10B02, 10D02, 11F02, 11F12, 12G12, 13H07, 14F10, 13C06, 13V07, 14E10, 13D12, 13A05, 13E04, 13E04, 14E04, 13E02, 13C10, 13E07, 13C03, 13B06, 1D6 and 15A2, does not reasonably provide enablement for the methods recited in claims 12-14 and 18-24. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims for the same reasons set forth in the previous Office Action mailed 10/07/2024 and 02/19/2025.
Further, the Claims encompass a genus of anti-galectin-10 antibodies.
The claims are directed to a broad class of antibodies was that the class was defined by its function—the ability to bind to galectin-10 and inhibiting galectin-10 crystal formation in a subject in need thereof, wherein the subject has a disease or condition including asthma, chronic rhinosinusitis, celiac disease, helminth infection, gastrointestinal eosinophilic inflammation, cystic fibrosis (CF), allergic bronchopulmonary aspergillosis (ABPA), Churg-Strauss vasculitis, chronic eosinophilic pneumonia, and acute myeloid leukemia. However, the specification did not give the skilled in the art enough information to choose candidate antibodies from the millions of options and therefore required scientists to engage in a great deal of experimentation and failure. “That is not enablement”—it is a “hunting license.”
The specification fails to provide a single example of anti-galectin-10 antibodies that binds a single amino acid within galectin-10 and inhibits galectin-10 crystal formation.
The Federal Circuit, citing McRO, provided guidance on the application of enablement to genus claims, holding that “[a]lthough a specification does not need to describe how to make and use every possible variant of the claimed invention, when a range is claimed, there must be reasonable enablement of the scope of the range.” Sanofi-Aventisub, 987 F.3d at 1085 (internal quotations omitted). Additionally, the Federal Circuit characterized Wyeth as holding “that due to the large number of possible candidates within the scope of the claims and the specification's corresponding lack of structural guidance, it would have required undue experimentation to synthesize and screen each candidate to determine which compounds in the claimed class exhibited the claimed functionality.” Id. at 1086. Similarly, the Federal Circuit characterized Enzo as holding “that the specification failed to teach one of skill in the art whether the many embodiments of the broad claims would exhibit that required functionality.” Id. Finally, the Federal Circuit characterized Idenix as affirming “the district court's determination that the claims had both structural and functional limitations, and that undue experimentation would have been required to synthesize and screen the billions of possible compounds because, given a lack of guidance across that full scope, finding functional compounds would be akin to finding a `needle in a haystack.' ” Id.
This case is akin to the issue in Sanofi-Aventisub, the court relied on evidence showing that the scope of the claims encompassed millions of antibodies and that it was necessary to screen each candidate antibody in order to determine whether it met the functional limitations of the claim. Id. at 1088. Consequently, the Federal Circuit concluded that there was a lack of enablement. While the specification in Amgen identified 26 exemplary antibodies that performed the claimed function by their amino acid sequences, the claims at issue were directed to a class that included “a `vast' number of additional antibodies” that Amgen had not described by their amino acid sequences. Id. at 1256. The Supreme Court found that Amgen sought to monopolize an entire class of antibodies by their function, which was much broader than the 26 exemplary antibodies disclosed by their amino acid structure. In the instant case, the specification discloses only two species that performed the claimed function by their amino acid sequences, with the claimed genus of millions of different anti-galectin-10 antibodies. The instant claims are directed to a class of anti-galectin-10 antibodies that included “a `vast' number of additional antibodies” that the instant specification fails to describe their amino acid sequences.
The scope of the instant claims encompassed millions of anti-galectin-10 antibodies and that it was necessary to first generate and then screen each candidate to determine whether it met the functional limitations. The Federal Circuit concluded that there was a lack of enablement, which was affirmed by the Supreme Court in Amgen.
The claims simply direct skilled artisans to engage in the same iterative, trial-and-error process the inventors followed to discover the two antibodies they elected to disclose and that “[u]nder Amgen, such random trial-and-error discovery, without more, constitutes unreasonable experimentation that falls outside the bounds required by § 112(a).” Id. at *8, *10.
Amgen attempted to claim an entire class of compounds by their function, namely antibodies that bind to the “sweet spot” of PCSK9 thereby inhibiting it from binding to LDL, while only describing 26 amino acid sequences in its specification. The two processes, the “roadmap” and “conservative substitution” did not save Amgen. According to the Court, these amounted to “little more than two research assignments” which forced scientists to conduct “painstaking experimentation” to see what worked. (citing Incandescent Lamp). The Court therefore held that Amgen’s specification did not enable the claims.
Applicant’s arguments, filed 05/19/2025, have been fully considered, but have not been found convincing.
Applicants submit the specification, provides sufficient evidence and disclosure to enable one of skill in the art to practice the full scope of the instantly claimed methods.
Applicant submits that the instant specification discloses results that show anti-galectin-10 antibodies are able to block formation of CLCs and solubilize existing CLCs, and that an anti- galectin-10 antibody can neutralize the effect of CLCs in vivo. The instant specification also provides a method for reproducibly generating large amounts of CLCs in vitro for functional studies and provides methods for administering the CLCs to mouse models to mimic features of human disease. Further, the instant specification provides methods for determining whether an anti-galectin-10 antibody blocks CLC formation, solubilizes CLCs in vitro or ex vivo, or blocks the effects of CLCs in vivo. The instant specification also describes the epitopes of galectin-10 to which the antibodies bind, and methods of generating anti-galectin-10 antibodies that are useful in the claimed methods. One of skill in the art could readily understand how to practice the claimed methods based on the extensive methods and data disclosed in the instant specification.
Applicants submit that the claims do not encompass methods of treating any disease. The claims encompass methods of inhibiting galectin-10 crystal formation or reducing the amount of galectin-10 crystals in a subject in need thereof. However, Applicant submits that the working example of a humanized mouse model correlates not only with asthma but with other diseases in humans that are highly associated with galectin-10 crystals or CLCs, as shown by the extensive in vitro data together with the in vivo data disclosed in the instant specification (as discussed above). CLCs were first reported in 1853 in the blood and spleen of a leukemia patient and have long been considered a hallmark of eosinophilic inflammation. The crystallized protein is found in body fluids and secretions in a variety of pathological conditions, including non-allergic diseases. See, e.g., Ueki et al., Curr Allergy Asthma Rep. 2019 Jun 15;19(8):35; and Su, J. Molecules. 2018 Nov 9;23(11):2931, provided herein, which describe studies showing CLCs in acute myeloid leukemia, solid tumors, helminth infection, fungal sinusitis, celiac disease, asthma, allergic rhinitis, and many others.
Applicants submit that based on the teachings and guidelines of the present invention as disclosed in the application, in combination with the knowledge of one of skill in the art at the time the application was filed, the instant specification enables a person of ordinary skill in the art to determine whether an anti-galectin-10 antibody blocks formation of CLCs or solubilizes preexisting CLCs, and to use it in the methods of the claims without undue experimentation.
This is not found persuasive because the asthma in a humanized mouse model does not represent the clamed conditions such as chronic rhinosinusitis; celiac disease; helminth infection; gastrointestinal eosinophilic inflammation; cystic fibrosis (CF); allergic bronchopulmonary aspergillosis (ABPA); Churg-Strauss vasculitis; chronic eosinophilic pneumonia; and acute myeloid leukemia. One cannot extrapolate the teachings of the specification to the scope of the claims because the claims are drawn to the treatment of patients suffering from chronic rhinosinusitis; celiac disease; helminth infection; gastrointestinal eosinophilic inflammation; cystic fibrosis (CF); allergic bronchopulmonary aspergillosis (ABPA); Churg-Strauss vasculitis; chronic eosinophilic pneumonia; and acute myeloid leukemia using the anti-galectin-10 antibodies. Besides treatment of asthma, no working empirical data demonstrating that the anti-galectin-10 antibodies would be use for the claimed diseases/conditions. The specification lacks empirical data on the in vivo efficacy of the anti-galectin-10 antibodies on patient including human. The experiments in the specification never successfully used the anti-galectin-10 antibody to treat chronic rhinosinusitis; celiac disease; helminth infection; gastrointestinal eosinophilic inflammation; cystic fibrosis (CF); allergic bronchopulmonary aspergillosis (ABPA); Churg-Strauss vasculitis; chronic eosinophilic pneumonia; and acute myeloid leukemia. In re Fisher, 166 USPQ 18 indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute.
8. 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.
9. Claims 18-21, 23-27, 29-30 and 32-34 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11713354 for the same reasons set forth in the previous Office Action mailed 10/07/2024 and 02/19/2025.
Applicant’s arguments, filed 05/19/2025, have been fully considered, but have not been found convincing.
Applicant asserts that the instant claims are not obvious in view of the claims of US Patent No. 11,713,354.
However, it remains the Examiner’s position that the claims of the `354 patent claims methods of inhibiting galectin-10 crystal formation in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an antibody or antigen binding fragment thereof which specifically binds to human galectin-10, wherein the subject has a disease or condition selected from the group consisting of asthma; chronic rhinosinusitis; celiac disease; helminth infection; gastrointestinal eosinophilic inflammation; cystic fibrosis (CF); allergic bronchopulmonary aspergillosis (ABPA); Churg-Strauss vasculitis; chronic eosinophilic pneumonia; and acute myeloid leukemia, and wherein the antibody or antigen binding fragment thereof cross competes for binding to human galectin-10 with an antibody or antigen binding fragment thereof comprising a variable heavy chain domain (VH) and a variable light chain domain (VL) wherein the VH and VL domains comprise the CDR sequences selected from the group consisting of: (i) HCDR3 comprising SEQ ID NO: 3, HCDR2 comprising SEQ ID NO: 2, HCDR1 comprising SEQ ID NO: 1, LCDR3 comprising SEQ ID NO: 58, LCDR2 comprising SEQ ID NO: 57, and LCDR1 comprising SEQ ID NO: 56; (ii) HCDR3 comprising SEQ ID NO: 9, HCDR2 comprising SEQ ID NO: 8, HCDR1 comprising SEQ ID NO: 7, LCDR3 comprising SEQ ID NO: 64, LCDR2 comprising SEQ ID NO: 63, and LCDR1 comprising SEQ ID NO: 62; (iii) HCDR3 comprising SEQ ID NO: 12, HCDR2 comprising SEQ ID NO: 11, HCDR1 comprising SEQ ID NO: 10, LCDR3 comprising SEQ ID NO: 67, LCDR2 comprising SEQ ID NO: 66, and LCDR1 comprising SEQ ID NO: 65; (iv) HCDR3 comprising SEQ ID NO: 25, HCDR2 comprising SEQ ID NO: 24, HCDR1 comprising SEQ ID NO: 4, LCDR3 comprising SEQ ID NO: 78, LCDR2 comprising SEQ ID NO: 77, and LCDR1 comprising SEQ ID NO: 76; (v) HCDR3 comprising SEQ ID NO: 47, HCDR2 comprising SEQ ID NO: 46, HCDR1 comprising SEQ ID NO: 45, LCDR3 comprising SEQ ID NO: 94, LCDR2 comprising SEQ ID NO: 93, and LCDR1 comprising SEQ ID NO: 71; (vi) HCDR3 comprising SEQ ID NO: 43, HCDR2 comprising SEQ ID NO: 42, HCDR1 comprising SEQ ID NO: 4, LCDR3 comprising SEQ ID NO: 94, LCDR2 comprising SEQ ID NO: 93, and LCDR1 comprising SEQ ID NO: 92; (vii) HCDR3 comprising SEQ ID NO: 6, HCDR2 comprising SEQ ID NO: 44, HCDR1 comprising SEQ ID NO: 4, LCDR3 comprising SEQ ID NO: 97, LCDR2 comprising SEQ ID NO: 96, and LCDR1 comprising SEQ ID NO: 95; (viii) HCDR3 comprising SEQ ID NO: 36, HCDR2 comprising SEQ ID NO: 52, HCDR1 comprising SEQ ID NO: 51, LCDR3 comprising SEQ ID NO: 98, LCDR2 comprising SEQ ID NO: 97, and LCDR1 comprising SEQ ID NO: 80; (ix) HCDR3 comprising SEQ ID NO: 55, HCDR2 comprising SEQ ID NO: 54, HCDR1 comprising SEQ ID NO: 53, LCDR3 comprising SEQ ID NO: 81, LCDR2 comprising SEQ ID NO: 93, and LCDR1 comprising SEQ ID NO: 71; (x) HCDR3 comprising SEQ ID NO: 50, HCDR2 comprising SEQ ID NO: 49, HCDR1 comprising SEQ ID NO: 48, LCDR3 comprising SEQ ID NO: 96, LCDR2 comprising SEQ ID NO: 63, and LCDR1 comprising SEQ ID NO: 95; (xi) HCDR3 comprising SEQ ID NO: 6, HCDR2 comprising SEQ ID NO: 5, HCDR1 comprising SEQ ID NO: 4, LCDR3 comprising SEQ ID NO: 61, LCDR2 comprising SEQ ID NO: 60, and LCDR1 comprising SEQ ID NO: 59; (xii) HCDR3 comprising SEQ ID NO: 165, HCDR2 comprising SEQ ID NO: 164, HCDR1 comprising SEQ ID NO: 163, LCDR3 comprising SEQ ID NO: 182, LCDR2 comprising SEQ ID NO: 181, and LCDR1 comprising SEQ ID NO: 180; (xiii) HCDR3 comprising SEQ ID NO: 174, HCDR2 comprising SEQ ID NO: 173, HCDR1 comprising SEQ ID NO: 172, LCDR3 comprising SEQ ID NO: 189, LCDR2 comprising SEQ ID NO: 188, and LCDR1 comprising SEQ ID NO: 180; and (xiv) HCDR3 comprising SEQ ID NO: 165, HCDR2 comprising SEQ ID NO: 164, HCDR1 comprising SEQ ID NO: 163, LCDR3 comprising SEQ ID NO: 193, LCDR2 comprising SEQ ID NO: 181, and LCDR1 comprising SEQ ID NO: 180.
Further the `354 patent claims methods of inhibiting galectin-10 crystal formation in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an antibody or antigen binding fragment thereof which specifically binds to human galectin-10, wherein: (a) the antibody or antigen binding fragment thereof comprises a VH and a VL wherein the VH and VL domains comprise the CDR sequences selected from the group consisting of: (i) HCDR3 comprising SEQ ID NO: 3, HCDR2 comprising SEQ ID NO: 2, HCDR1 comprising SEQ ID NO: 1, LCDR3 comprising SEQ ID NO: 58, LCDR2 comprising SEQ ID NO: 57, and LCDR1 comprising SEQ ID NO: 56; (ii) HCDR3 comprising SEQ ID NO: 6, HCDR2 comprising SEQ ID NO: 5, HCDR1 comprising SEQ ID NO: 4, LCDR3 comprising SEQ ID NO: 61, LCDR2 comprising SEQ ID NO: 60, and LCDR1 comprising SEQ ID NO: 59; (iii) HCDR3 comprising SEQ ID NO: 9, HCDR2 comprising SEQ ID NO: 8, HCDR1 comprising SEQ ID NO: 7, LCDR3 comprising SEQ ID NO: 64, LCDR2 comprising SEQ ID NO: 63, and LCDR1 comprising SEQ ID NO: 62; (iv) HCDR3 comprising SEQ ID NO: 12, HCDR2 comprising SEQ ID NO: 11, HCDR1 comprising SEQ ID NO: 10, LCDR3 comprising SEQ ID NO: 67, LCDR2 comprising SEQ ID NO: 66, and LCDR1 comprising SEQ ID NO: 65; (v) HCDR3 comprising SEQ ID NO: 15, HCDR2 comprising SEQ ID NO: 14, HCDR1 comprising SEQ ID NO: 13, LCDR3 comprising SEQ ID NO: 70, LCDR2 comprising SEQ ID NO: 69, and LCDR1 comprising SEQ ID NO: 68; (vi) HCDR3 comprising SEQ ID NO: 18, HCDR2 comprising SEQ ID NO: 17, HCDR1 comprising SEQ ID NO: 16, LCDR3 comprising SEQ ID NO: 72, LCDR2 comprising SEQ ID NO: 66, and LCDR1 comprising SEQ ID NO: 71; (vii) HCDR3 comprising SEQ ID NO: 20, HCDR2 comprising SEQ ID NO: 19, HCDR1 comprising SEQ ID NO: 4, LCDR3 comprising SEQ ID NO: 75, LCDR2 comprising SEQ ID NO: 74, and LCDR1 comprising SEQ ID NO: 73; (viii) HCDR3 comprising SEQ ID NO: 23, HCDR2 comprising SEQ ID NO: 22, HCDR1 comprising SEQ ID NO: 21, LCDR3 comprising SEQ ID NO: 67, LCDR2 comprising SEQ ID NO: 66, and LCDR1 comprising SEQ ID NO: 65; (ix) HCDR3 comprising SEQ ID NO: 25, HCDR2 comprising SEQ ID NO: 24, HCDR1 comprising SEQ ID NO: 4, LCDR3 comprising SEQ ID NO: 78, LCDR2 comprising SEQ ID NO: 77, and LCDR1 comprising SEQ ID NO: 76; (x) HCDR3 comprising SEQ ID NO: 28, HCDR2 comprising SEQ ID NO: 27, HCDR1 comprising SEQ ID NO: 26, LCDR3 comprising SEQ ID NO: 67, LCDR2 comprising SEQ ID NO: 66, and LCDR1 comprising SEQ ID NO: 79; (xi) HCDR3 comprising SEQ ID NO: 31, HCDR2 comprising SEQ ID NO: 30, HCDR1 comprising SEQ ID NO: 29, LCDR3 comprising SEQ ID NO: 81, LCDR2 comprising SEQ ID NO: 63, and LCDR1 comprising SEQ ID NO: 80; (xii) HCDR3 comprising SEQ ID NO: 33, HCDR2 comprising SEQ ID NO: 32, HCDR1 comprising SEQ ID NO: 1, LCDR3 comprising SEQ ID NO: 84, LCDR2 comprising SEQ ID NO: 83, and LCDR1 comprising SEQ ID NO: 82; (xiii) HCDR3 comprising SEQ ID NO: 36, HCDR2 comprising SEQ ID NO: 35, HCDR1 comprising SEQ ID NO: 34, LCDR3 comprising SEQ ID NO: 87, LCDR2 comprising SEQ ID NO: 86, and LCDR1 comprising SEQ ID NO: 85; (xiv) HCDR3 comprising SEQ ID NO: 38, HCDR2 comprising SEQ ID NO: 11, HCDR1 comprising SEQ ID NO: 37, LCDR3 comprising SEQ ID NO: 78, LCDR2 comprising SEQ ID NO: 63, and LCDR1 comprising SEQ ID NO: 88; (xv) HCDR3 comprising SEQ ID NO: 41, HCDR2 comprising SEQ ID NO: 40, HCDR1 comprising SEQ ID NO: 39, LCDR3 comprising SEQ ID NO: 91, LCDR2 comprising SEQ ID NO: 90, and LCDR1 comprising SEQ ID NO: 89; (xvi) HCDR3 comprising SEQ ID NO: 43, HCDR2 comprising SEQ ID NO: 42, HCDR1 comprising SEQ ID NO: 4, LCDR3 comprising SEQ ID NO: 94, LCDR2 comprising SEQ ID NO: 93, and LCDR1 comprising SEQ ID NO: 92; (xvii) HCDR3 comprising SEQ ID NO: 6, HCDR2 comprising SEQ ID NO: 44, HCDR1 comprising SEQ ID NO: 4, LCDR3 comprising SEQ ID NO: 97, LCDR2 comprising SEQ ID NO: 96, and LCDR1 comprising SEQ ID NO: 95; (xviii) HCDR3 comprising SEQ ID NO: 47, HCDR2 comprising SEQ ID NO: 46, HCDR1 comprising SEQ ID NO: 45, LCDR3 comprising SEQ ID NO: 94, LCDR2 comprising SEQ ID NO: 93, and LCDR1 comprising SEQ ID NO: 71; (xix) HCDR3 comprising SEQ ID NO: 50, HCDR2 comprising SEQ ID NO: 49, HCDR1 comprising SEQ ID NO: 48, LCDR3 comprising SEQ ID NO: 96, LCDR2 comprising SEQ ID NO: 63, and LCDR1 comprising SEQ ID NO: 95; (xx) HCDR3 comprising SEQ ID NO: 36, HCDR2 comprising SEQ ID NO: 52, HCDR1 comprising SEQ ID NO: 51, LCDR3 comprising SEQ ID NO: 98, LCDR2 comprising SEQ ID NO: 97, and LCDR1 comprising SEQ ID NO: 80; and (xxi) HCDR3 comprising SEQ ID NO: 55, HCDR2 comprising SEQ ID NO: 54, HCDR1 comprising SEQ ID NO: 53, LCDR3 comprising SEQ ID NO: 81, LCDR2 comprising SEQ ID NO: 93, and LCDR1 comprising SEQ ID NO: 71; (xxii) HCDR3 comprising SEQ ID NO: 162, HCDR2 comprising SEQ ID NO: 161, HCDR1 comprising SEQ ID NO: 160, LCDR3 comprising SEQ ID NO: 179, LCDR2 comprising SEQ ID NO: 178, and LCDR1 comprising SEQ ID NO: 177; (xxiii) HCDR3 comprising SEQ ID NO: 165, HCDR2 comprising SEQ ID NO: 164, HCDR1 comprising SEQ ID NO: 163, LCDR3 comprising SEQ ID NO: 182, LCDR2 comprising SEQ ID NO: 181, and LCDR1 comprising SEQ ID NO: 180; (xxiv) HCDR3 comprising SEQ ID NO: 168, HCDR2 comprising SEQ ID NO: 167, HCDR1 comprising SEQ ID NO: 166, LCDR3 comprising SEQ ID NO: 185, LCDR2 comprising SEQ ID NO: 184, and LCDR1 comprising SEQ ID NO: 183; (xxv) HCDR3 comprising SEQ ID NO: 171, HCDR2 comprising SEQ ID NO: 170, HCDR1 comprising SEQ ID NO: 169, LCDR3 comprising SEQ ID NO: 187, LCDR2 comprising SEQ ID NO: 186, and LCDR1 comprising SEQ ID NO: 180; (xxvi) HCDR3 comprising SEQ ID NO: 174, HCDR2 comprising SEQ ID NO: 173, HCDR1 comprising SEQ ID NO: 172, LCDR3 comprising SEQ ID NO: 189, LCDR2 comprising SEQ ID NO: 188, and LCDR1 comprising SEQ ID NO: 180; (xxvii) HCDR3 comprising SEQ ID NO: 176, HCDR2 comprising SEQ ID NO: 175, HCDR1 comprising SEQ ID NO: 163, LCDR3 comprising SEQ ID NO: 192, LCDR2 comprising SEQ ID NO: 191, and LCDR1 comprising SEQ ID NO: 190; and (xxviii) HCDR3 comprising SEQ ID NO: 165, HCDR2 comprising SEQ ID NO: 164, HCDR1 comprising SEQ ID NO: 163, LCDR3 comprising SEQ ID NO: 193, LCDR2 comprising SEQ ID NO: 181, and LCDR1 comprising SEQ ID NO: 180; or (b) the antibody comprises a VHH domain comprising the CDR sequences selected from the group consisting of: (i) CDR3 comprising SEQ ID NO: 210, CDR2 comprising SEQ ID NO: 209, and CDR1 comprising SEQ ID NO: 208; (ii) CDR3 comprising SEQ ID NO: 213, CDR2 comprising SEQ ID NO: 212, and CDR1 comprising SEQ ID NO: 211; (iii) CDR3 comprising SEQ ID NO: 216, CDR2 comprising SEQ ID NO: 215, and CDR1 comprising SEQ ID NO: 214; (iv) CDR3 comprising SEQ ID NO: 219, CDR2 comprising SEQ ID NO: 218, and CDR1 comprising SEQ ID NO: 217; (v) CDR3 comprising SEQ ID NO: 222, CDR2 comprising SEQ ID NO: 221, and CDR1 comprising SEQ ID NO: 220; (vi) CDR3 comprising SEQ ID NO: 225, CDR2 comprising SEQ ID NO: 224, and CDR1 comprising SEQ ID NO: 223; (vii) CDR3 comprising SEQ ID NO: 228, CDR2 comprising SEQ ID NO: 227, and CDR1 comprising SEQ ID NO: 226; (viii) CDR3 comprising SEQ ID NO: 231, CDR2 comprising SEQ ID NO: 230, and CDR1 comprising SEQ ID NO: 229; (ix) CDR3 comprising SEQ ID NO: 234, CDR2 comprising SEQ ID NO: 233, and CDR1 comprising SEQ ID NO: 232; (x) CDR3 comprising SEQ ID NO: 236, CDR2 comprising SEQ ID NO: 235, and CDR1 comprising SEQ ID NO: 226; (xi) CDR3 comprising SEQ ID NO: 238, CDR2 comprising SEQ ID NO: 237, and CDR1 comprising SEQ ID NO: 232; (xii) CDR3 comprising SEQ ID NO: 241, CDR2 comprising SEQ ID NO: 240, and CDR1 comprising SEQ ID NO: 239; (xiii) CDR3 comprising SEQ ID NO: 236, CDR2 comprising SEQ ID NO: 235, and CDR1 comprising SEQ ID NO: 226; (xiv)