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 .
Claim Status
The original claim set filed 12 March 2024 is acknowledged. Claims 1-16 are currently pending. No claims are cancelled. Claims 1-16 will be examined on the merits herein.
For clarity of the record, references to the specification will use paragraph numbers from the Pre-Grant Publication US-20240383950-A1 in order to avoid ambiguity caused by different versions of the specification having the text located at different page and line numbers.
Priority
The application claims priority to IN202121044592 (filed 1 Oct 2021) and is a 371 of PCT/IB2022/059341 (filed 30 Sep 2022). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. What follows is the examiner’s claim-by-claim analysis of effective filing date for the claims currently under examination. If the applicant disagrees with this examiner’s determination of effective filing date for any claim, the applicant may identify text within the prior applications that provides support the claimed language.
For claim 1 (and dependent claims 1-16), the foreign priority document does not provide support for generic variants with any additional cysteine at the carboxy-terminal end. The word “terminal” is used twice and neither context is a generic teaching of adding a cysteine (as well as potentially other amino acids). The word “cysteine” is used five times. Once is a specific teaching of SEQ ID NO: 5, which is a specific variant with a cysteine added at the 143rd position (pg. 26), once is a teaching that the lectin may be linked to other objects in a variety of ways such as free amino moieties, free thiol moieties (such as the ones in cysteine), or free acid groups (pg. 34), but there is no teaching to modify the generic claimed lectin variants to add a cysteine. There is a teaching that a cleavable unit G may include 1-12 amino acids that is each “independently selected from the group consisting of alanine, arginine, aspartic acid, asparagine, histidine, glycine, glutamic acid, glutamine, phenylalanine, lysine, leucine, serine, tyrosine, threonine, isoleucine, proline, tryptophan, valine, cysteine, methionine, selenocysteine, ornithine, penicillamine, ß-alanine, aminoalkanoic acid, aminoalkynoic acid, aminoalkanedioic acid, aminobenzoic acid, amino-heterocyclo-alkanoic acid, heterocyclo-carboxylic acid, citrulline, statine, diaminoalkanoic acid, and derivatives thereof” (pg. 43), but one of ordinary skill in the art would not understand this as a teaching to modify the claimed lectin to add a cysteine given the broad range of amino acids listed. There is a teaching that the lectin (L) can be “linked to succinimide or maleimide group via Sulphur of thiol group present in cysteine” (pg. 46), but SEQ ID NO: 1 already has a cysteine, so one of ordinary skill in the art would not understand this as a teaching to add a cysteine, and especially not to add one at the C-terminal end. There is a teaching of one specific conjugate in Example 7 that is linked via a cysteine (pg. 80), which is also disclosed at page 23, lines 11-15 (SEQ ID NO:5), but one of ordinary skill in the art would not understand this one specific disclosed sequence as a teaching of generic variants with any additional cysteine at the C-terminal end. The single species is not representative of broad genus claimed of all possible variants comprising a cysteine and any other amino acids, in any order.
For claims 3, 5-6, these cysteine-related limitations are also not taught in the foreign priority document, see the summary of uses of the word “cysteine” that are discussed for claim 1.
For claim 4, the foreign priority document teaches specifically SEQ ID NO: 5, which is a specific variant with a T1S mutation (pg. 26), but this does not support this modification on any of the generic lectin variants of claim 1. Searches for “threonine” and “position” did not reveal a generic teaching to modify position 1 substitute threonine with serine.
For claim 8, the teaching of the modifications to make SEQ ID NO: 5 (pg. 26) is the same as the modifications to make instant SEQ ID NO: 3 [0050]. However, there is not support in the foreign priority document for the combination of modifications to make instant SEQ ID NO: 4 [0051].
Therefore, the effective filing date used for searching the art is 30 Sep 2022 for all claims.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 10 Jun 2024 (2x) were both filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner. Signed copies of these statements are attached with this action.
Drawings
The drawings are objected to under 37 CFR 1.83(a) because they fail to show experimental results as described in the specification. The image is so unclear that the image cannot be interpreted, and label text (if present) is completely illegible. The examiner’s view of the figure is copied below.
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Examiner’s view of Figure 5.
Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities:
The tables in Example 6 [0091] are labeled Fig. 1 and Fig. 2; however, these tables are not figures. Figures 1-2 are protein gels. The specification should not use the same label to refer to two different objects.
The table in Example 2 is labeled Table 1, but the subsequent table in Example 3 is labeled Table 3. There is no Table 2. To avoid confusion, table labels should use consecutive numbers and should not skip numbers.
Applicant should be aware that only some tables are labeled with a “Table #” label. A numerical label for each table is not required by the MPEP and is not being required by the Examiner, but applicant may wish to add table labels for easier reference to the data presented in the tables.
Appropriate correction is required.
Claim Objections
Claim 1 is objected to because of the following informalities: the species name Sclerotium rolfsii should be italicized to match naming conventions in the art at the time of filing. Appropriate correction is required.
Claim 11 is objected to because of the following informalities: minor grammatical error due to a missing article, claim should read “the agent”. Appropriate correction is required.
Claim Interpretation
Regarding the fungal species referenced in all claims, the art teaches that Athelia rolfsii and Sclerotium rolfsii are alternate, synonymous names for the same species of fungus, see evidence in Pethylbridge et al. (2019; PTO-892; Abstract). Both genus names have been searched. For clarity, only the name Sclerotium rolfsii will be used in this action to match the name used in the instant specification.
For claims 4-7, the claims define mutations using amino acid positions on the variant. The broadest reasonable interpretation of the term “variant” includes proteins that are fragments of the original SRL protein, so position 1 or 76 of the variant does not necessarily align with position 1 or 76 of SEQ ID NO: 1. Also, positions 142 and 143 of the variant do not necessarily follow the amino acid aligning with position 141 of SEQ ID NO: 1. For example, a variant that is amino acids 3-50 of SEQ ID NO: 1, and an additional cysteine at the carboxy terminal end, would have a K to S substitution at position 1 of the variant (corresponding to position 3 of SEQ ID NO: 1) and would not have any position 76 for a substitution at all. For example, a variant that has amino acids N-terminally fused to SEQ ID NO: 1 would already have amino acids present at positions 142-143 of the variant, so the modification would be a substitution mutation rather than an addition of new amino acids. Therefore, claims 4-7 are interpreted as product-by-process mutations. The search will include all variants with a S at position 1, a G at position 76, a C at position 142, or a SC at positions 142-143, even if the pre-mutation amino acid differs from what is described in the claim or the modification is a substitution rather than an “addition”.
See MPEP 2113: "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted). … However, in the context of an infringement analysis, a product-by-process claim is only infringed by a product made by the process recited in the claim. Id. at 1370 ("a product in the prior art made by a different process can anticipate a product-by-process claim, but an accused product made by a different process cannot infringe a product-by-process claim").”
Regarding claim 16, the term “transfected” describes a specific process by which a nucleic acid can be added to a cell. Demetriou et al. (US-20180169260-A1; PTO-892) teaches that in addition to transfection, a cell can also be transformed or transduced to introduce nucleic acids into a host cell [0114]. Therefore, claim 16 is interpreted as a product-by-process claim. The search will include all cells comprising the polynucleotide, even if the cell was not made by the process of transfection. See the MPEP support for this decision above (par. 20).
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-16 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 1, the claim reads “a variant of Sclerotium rolfsii Lectin (SRL) represented by SEQ ID NO:1”. Due to unclear antecedent basis, one of ordinary skill in the art would not be able to determine whether the variant or the original SRL is what is “represented by SEQ ID NO:1”. Dependent claims 2-16 are also rejected under this grounds because they depend from claim 1 and do not overcome the rejection. Clarification is requested. In the interest of compact prosecution, in this action the claim will be interpreted as the original SRL having SEQ ID NO: 1, and the variant not being required to comprise SEQ ID NO: 1, because SEQ ID NO: 1 does not have a cysteine at the carboxy terminal end and because dependent claim 2 broadens the variant sequences beyond comprising SEQ ID NO: 1.
Regarding claim 1, the claim reads “Thomsen-Friedenreich (Galpl-3GalNAca-O-Ser/Thr, TF or T) antigen, 0-GalNAc Core1 (T antigen)” and “'α2,3/6-sialyl Core1' (Sialyl-T antigen)”. The meaning of the phrases inside the parentheses is indefinite and cannot be determined from the context of the claim or specification. If the parenthetical phrases are intended as defining the terms, then the claim is indefinite because both Thomsen-Friedenreich antigen and 0-GalNAc Core1 are defined as T antigen. If the parenthetical phrases are intended as examples of the Thomsen-Friedenreich antigen, 0-GalNAc Core1 and 'α2,3/6-sialyl Core1', then the parenthetical phrase with the same meaning as "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Dependent claims 2-15 are also rejected under this grounds because they depend from claim 1 and do not overcome the rejection. Clarification is requested. In the interest of compact prosecution, in this action the claim will be interpreted as being met if any of the listed names are present in the reference (for example, a reference to T antigen is interpreted as both Thomsen-Friedenreich antigen and 0-GalNAc Core1), unless context unambiguously indicates otherwise.
Regarding claim 3, the claim states “the variant is devoid of cysteine (C) at amino acid positions between 1 and 141 of SEQ ID NO: 1.” The claim is indefinite because the antecedent basis of the term “amino acid position” is insufficient because one of ordinary skill in the art would not be able to determine whether the positions 1-141 being measured are from the variant protein sequence or from SEQ ID NO: 1. This ambiguity affects determining the claim scope because the broadest reasonable interpretation of the term “variant” includes proteins that are fragments of the original SRL protein so positions 1-141 of SEQ ID NO: 1 are not necessarily all present in the variant and the variant may not even have 141 amino acids total, and the term “variant” also includes proteins that have N-terminal insertions before the original SRL protein so positions 1-141 of SEQ ID NO: 1 do not correspond with positions 1-141 of the variant. In the interest of compact prosecution, in this action the claim will be interpreted as the variant being devoid of cysteine at amino acids that align with positions 1-141 of SEQ ID NO: 1.
Regarding claim 8, the claim recites “the protein is represented by SEQ ID NO. 3 or SEQ ID NO. 4.” One of ordinary skill in the art would not be able to determine claim scope because it is not apparent whether “represented by” is open claim language (like comprising) or closed claim language (like consisting of). In the interest of compact prosecution, in this action the claim will be interpreted as open claim language.
Regarding claims 11-13, the claims limit how the protein is used, rather than limiting the structure of the protein. MPEP 2173.05(p) states: “A single claim which claims both an apparatus and the method steps of using the apparatus is indefinite under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. See In re Katz Interactive Call Processing Patent Litigation, 639 F.3d 1303, 1318, 97 USPQ2d 1737, 1748-49 (Fed. Cir. 2011). In Katz, a claim directed to "[a] system with an interface means for providing automated voice messages…to certain of said individual callers, wherein said certain of said individual callers digitally enter data" was determined to be indefinite because the italicized claim limitation is not directed to the system, but rather to actions of the individual callers, which creates confusion as to when direct infringement occurs. Katz, 639 F.3d at 1318, 97 USPQ2d at 1749 (citing IPXL Holdings v. Amazon.com, Inc., 430 F.3d 1377, 1384, 77 USPQ2d 1140, 1145 (Fed. Cir. 2005), in which a system claim that recited "an input means" and required a user to use the input means was found to be indefinite because it was unclear "whether infringement … occurs when one creates a system that allows the user [to use the input means], or whether infringement occurs when the user actually uses the input means."); Ex parte Lyell, 17 USPQ2d 1548 (Bd. Pat. App. & Inter. 1990) (claim directed to an automatic transmission workstand and the method of using it held ambiguous and properly rejected under 35 U.S.C. 112, second paragraph)” In this case, as in the cases cited in the MPEP, the claim includes both a product (a protein) and a use for the protein product, which makes the claims indefinite because it is unclear whether infringement occurs when the protein is created or when it is used as described in claims 11-13. In the interest of compact prosecution, in this action the claimed uses will be interpreted as intended uses that are anticipated if the product is capable of use in the claimed manner, as described in MPEP 2111.02.
Regarding claim 12, the claim recites “the protein is used for preparation of medicament for treatment of cancer.” MPEP 2173.05(q) states: “Attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph.” This claim tries to limit the protein’s use, but does not describe any steps that are actually involved in the “preparation of medicament”. So one of ordinary skill in the art would not be able to determine that types of uses/preparations are claimed.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP 2163 states:
An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement is not necessarily met when the claim language appears in ipsis verbis in the specification. "Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement." Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002).
Thus, the written description requirement may be satisfied through disclosure of function and minimal structure when there is a well-established correlation between structure and function. In contrast, without such a correlation, the capability to recognize or understand the structure from the mere recitation of function and minimal structure is highly unlikely. In this latter case, disclosure of function alone is little more than a wish for possession; it does not satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (written description requirement not satisfied by merely providing "a result that one might achieve if one made that invention"); In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming a rejection for lack of written description because the specification does "little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate").
This rejection is related to the possession of SRL variants that can to bind to generic “modified forms of TF and T antigens” from claim 1 and the possession of variants that have mutations at defined amino acid positions, even though those amino acid position numbers do not necessarily correspond to the same part of the protein in as the original SRL sequence, as in claims 3-7.
First, the claims are drawn to recombinant glycan binding proteins that comprise a SRL variant whose structure is only defined as “compris[ing] an additional cysteine at carboxy terminal end”, but which must have the function of “retains binding affinity toward one or more antigens selected from Thomsen-Friedenreich (Galpl-3GalNAca-O-Ser/Thr, TF or T) antigen, 0-GalNAc Corel (T antigen), Core2, 'u2,3/6-sialyl Corel' (Sialyl-T antigen), 'u2,6/6-sialyl Core2' and modified forms of TF and T antigens”. The broadest reasonable interpretation of “modified forms of TF and T antigens” is broad and includes highly varied sugar structures, such as changing sugar monomer types, changing linkages between the sugars, etc.
The instant specification measured what types of glycans are bound by the SRL protein with SEQ ID NO: 2 [Example 3]. This protein does not fall within the scope of claimed variants because it only has one cysteine at position 76 (i.e. does not comprise an additional cysteine at carboxy terminal end). The instant specification teaches “The Lectin having SEQ ID NO: 2 showed specific binding to N-glycans containing GlcNac at the non-reducing end;… Lectin having SEQ ID NO:2 showed strong and broad binding profile to O-glycans, specifically to T-antigen and its extended core structures” [0075-0076]. So, the binding properties of SRL vary depending on the type of linkage (N-linked or O-linked). The specification does not teach what variations of the SRL protein will make the protein able to bind modified versions of the sugars that have different linkages.
The art teaches the structure of wild-type, unmodified SRL and the interactions between the protein and the sugars that it binds. Leonidas et al. (2007; PTO-892) teaches “The crystal structures of the SRL in complex with two carbohydrates, GalNAc and GlcNAc, which differ only in the configuration of a single epimeric hydroxyl group,” (Abstract). Despite the high similarity of these two sugars, they interact with the SRL protein at completely different sites: “GalNAc binds at the primary site, whereas GlcNAc binds only at the secondary site” (Abstract). Peppa et al. (2015; PTO-892) created two recombinant variants of SRL, SSR1 and SSR2. “[D]eliberate replacement of the amino acid is incorporated between SRL and SSR1 at 14th, 113th and 123rd positions, where the amino acids Asn, Glu and Glu residues were replaced by Asp, Gln and Gln, respectively. In case of SSR2 amino acids at the 1st, 14th, 34th, 113th and 123rd were replaced with Val, Asp, Ser, Gln and Gln, respectively” (pg. 10851 col. 2, Figure 2). Peppa et al. also published SRL protein structures highlighting the modified amino acids (Figure 2). Peppa et al. found that SSR1 had a modified glycan affinity compared to SRL, but SSR2 had an unaltered glycan affinity (Abstract).
One of ordinary skill in the art would believe that the instant specification demonstrated possession of SRL variants that retain the existing SRL carbohydrate-binding surfaces and the resulting existing SRL carbohydrate-binding properties, due to the well-known wild-type SRL structure that was published in multiple references beginning more than 10 years before the effective filing date, and due to the high level of skill in the art. See MPEP 2163: “What is conventional or well known to one of ordinary skill in the art need not be disclosed in detail. See Hybritech Inc. v. Monoclonal Antibodies, Inc., 802 F.2d at 1384, 231 USPQ at 94.”
However, one of ordinary skill in the art would not believe that the specification demonstrated possession of variant SRL proteins capable of binding to modified forms of the TF or T sugar antigens, because the instant specification did not describe how to modify the SRL structure to change its binding properties and both the specification and the art show that SRL-sugar binding is highly specific (i.e. the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved, see MPEP 2163). Therefore, one of ordinary skill in the art would not believe that the species variant SRL proteins that bind to unmodified TF and T antigens is representative of the broader genus of variant SRL proteins that bind to the broader genus of modified TF and T antigens (i.e. a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated, see MPEP 2163).
Second, the dependent claims 4-7 define mutations using amino acid positions on the variant. The broadest reasonable interpretation of the term “variant” includes proteins that are fragments of the original SRL protein or proteins that could have additional N-terminal amino acids before the beginning of the fragment corresponding to SEQ ID NO: 1. So position 1 or 76 of the variant does not necessarily correspond structurally to position 1 or 76 of SEQ ID NO: 1, and positions 142 and 143 of the variant do not necessarily follow the amino acid corresponding to position 141 of SEQ ID NO: 1. For example, a variant that is amino acids 3-50 of SEQ ID NO: 1, and an additional cysteine at the carboxy terminal end, would have a K to S substitution at position 1 of the variant (corresponding to position 3 of SEQ ID NO: 1) and would not have any position 76 for a substitution at all. For example, a variant that has amino acids N-terminally fused to SEQ ID NO: 1 would already have amino acids present at positions 142-143 of the variant, so the modification would be a substitution mutation rather than an addition of new amino acids.
The instant specification describes the claimed mutations as having specific functions related to the structure of the unmodified SRL protein. The substitution at position 1 of SEQ ID NO: 2 is performed to remove the threonine and aid in the efficient removal of an N-terminal Methionine at the zero position [0047]. The substitution at position 76 of SEQ ID NO: 2 is performed to remove a cysteine that could form an undesired disulfide bond [0049]. The specification describes the 142nd position as being at the carboxy terminal end of SEQ ID NO: 2 [0049], and the modification at the 142nd and 143rd positions is described as “The addition of Serine at 142nd position may aid in providing the space and flexibility between the c-terminal cystine and the protein, further providing flexibility to the conjugated drug” [0051]. The specification does not discuss how to modify the mutations when making variants that are fragments of SRL and does not discuss the possibility of N-terminal insertions before SRL.
As discussed above (par. 32-33), the specification and art show that the protein-sugar binding structure is highly specific. So one of ordinary skill in the art know that a mutation to a specific amino acid position of the SRL variant would not be correlated with the required function of binding to the sugar antigens unless mutation occurs at the defined place in the protein’s structure (i.e. the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved, see MPEP 2163). Also, the specification describes a broad genus of SRL variants which have mutations throughout the protein due to the breadth of the term “variant” including fragments or proteins with N-terminal insertions, but the specification only describes the narrow species of SRL variants that have mutations at one specific location that aligns with the same amino acid position number of the original SRL sequence (i.e. a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated, see MPEP 2163).
For these reasons, claims 1-16 are rejected as lacking adequate written description because each claim has at least one of the problems discussed above.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1 and 9-16 are rejected under 35 U.S.C. 102(a)(1) as anticipated by Demetriou et al. (US-20180169260-A1; hereafter Demetriou; PTO-892).
Regarding claims 1, 12-13, Demetriou teaches “a composition for treating cancer comprising a peptide comprising a tumor-associated carbohydrate antigen (TACA)-binding domain derived from a lectin, wherein the TACA-binding domain specifically binds to a TACA of a tumor cell” [0006]. The lectin can be Sclerotium rolfsii lectin (SRL) [0007]. No protein sequence is provided, but claim 1 does not require that the variant have any particular sequence (see the interpretation laid out in the 112(b) rejection above). Specifically, the tumor-binding peptide is an Fc fusion protein comprising the TACA-binding domain that “further comprises a domain that specifically binds to an immune effector cell” [0011-0012], and the immune effector cell-binding domain can have the sequence of SEQ ID NO: 9 [0013]. Inspection reveals that this sequence comprises several cysteines (see also alignment below). The example peptide SEQ ID NO: 11 [0013] teaches that the immune effector cell-binding SEQ ID NO: 9 is found at the carboxy terminal (C-terminal) end of the protein, following the example peptide’s TACA-binding domain. So, Demetriou teaches a recombinant glycan binding protein that comprises a variant of SRL (varied by being in a fusion protein), that comprises additional cysteines at the C-terminal end from the cysteines in SEQ ID NO: 9. Additionally, Demetriou also teaches that the protein of the invention can be made into a cyclic derivative by adding cysteines at the “right and left position” (i.e. N- and C-terminal) and forming a disulfide bond between them [0166-0167].
There is no evidence of record that the binding affinity of the SRL variant would change (i.e. it retains binding affinity toward one or more antigens selected from Thomsen-Friedenreich (Galpl-3GalNAca-O-Ser/Thr, TF or T) antigen, 0-GalNAc Corel (T antigen), Core2, 'u2,3/6-sialyl Corel' (Sialyl-T antigen), 'u2,6/6-sialyl Core2' and modified forms of TF and T antigens), particularly because Demetriou is using the protein for its carbohydrate-binding ability. MPEP 2112.01 states: when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. In this case, the structure is substantially the same (the SRL carbohydrate-binding region), so the specific sugars bound by the SRL variant are assumed to be inherent, absent evidence to the contrary.
Regarding claims 9-11, the SRL variant is conjugated to a agent that is the T-cell binding domain of the Fc fusion protein, which is an anti-cancer agent.
Regarding claim 14, Demetriou teaches pharmaceutical compositions comprising the protein and excipients [0282].
Regarding claim 15, Demetriou teaches a nucleic acid encoding the peptide encoding the TACA domain [0175], and teaches that the nucleic acid can be made by recombinant methods [0185].
Regarding claim 16, Demetriou teaches a cell modified to express the peptide [0255], and teaches that specifically transfected cells can be used [0258].
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Figure 1: Alignment of Demetriou SEQ ID NO: 9 (immune effector cell-binding domain) with SEQ ID NO: 11 (example full cancer treating peptide). SEQ ID NO: 9 is found at the C-terminus of the protein.
Claims 1-5 and 11-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sathe et al. (WO-2020044296-A2; hereafter Sathe; PTO-892).
Regarding claim 1, Sathe teaches “modified lectin protein is provided having at least one amino acid modification in an amino acid sequence of SEQ ID NO. 1” [Abstract], these proteins are recombinant [Title]. Sathe teaches modified SRL having an amino acid substitution [pg. 21 par 2] that can include a R105C modification that introduces an additional cysteine within the C-terminal end of the SRL protein [pg. 22 par. 2 (d)]. As the term “C-terminal end” has not been defined in the in the instant specification, it is understood broadly as referring to the final part (“end”) of the existing SRL amino acid sequence or following the existing SRL amino acid sequence.
There is no evidence of record that the binding affinity of the SRL variant would change (i.e. it retains binding affinity toward one or more antigens selected from Thomsen-Friedenreich (Galpl-3GalNAca-O-Ser/Thr, TF or T) antigen, 0-GalNAc Corel (T antigen), Core2, 'u2,3/6-sialyl Corel' (Sialyl-T antigen), 'u2,6/6-sialyl Core2' and modified forms of TF and T antigens). MPEP 2112.01 states: when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. In this case, the structure is substantially the same (the SRL carbohydrate-binding region), so the specific sugars bound by the SRL variant are assumed to be inherent, absent evidence to the contrary.
Regarding claim 2, the Sathe modified SRL with the R105C and C76G mutations (see discussion of claims 3 and 5 below) has 98.6% identity with instant SEQ ID NO: 1 (see alignment following the rejection).
Regarding claim 3 and 5, Sathe teaches “it is believed that the cysteine residue at position 76 of SEQ ID NO. 1 mediates dimer formation though the formation of a disulphide linkage. In certain embodiments, it is preferable to reduce dimer formation such that only one form of the protein (i.e. the monomeric form) is present. Thus in a fourth embodiment of the present invention, the modified lectin protein contains an amino acid substitution at position 76 of SEQ ID NO. 1 or a corresponding position of a sequence having at least 60% homology thereto such that the amino acid residue at that position is no longer cysteine. In a preferred embodiment, the substituting amino acid (i.e. that which replaces the original amino acid) at position 76 is glycine.” [pg. 25 par. 1-2].
Regarding claim 4, Sathe teaches the protein can have an amino acid substitution at position 1 where the final amino acid is serine [pg. 8 par. 3].
Regarding claims 11-13, the modified lectin of Sathe is presumed to be capable of use for these functions. MPEP 2112.01 states: when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. In this case, the structure is substantially the same (the SRL carbohydrate-binding region), so the specific functions that the protein is capable of performing are presumed to be inherent, absent evidence to the contrary. Also, regarding claim 12-13, Sathe teaches that the modified lectin can be used for detection of a cancer cell, cancer diagnosis and/or cancer therapy, and can be administered in a pharmaceutical composition (i.e. used for preparation of medicament for treatment of cancer) [pg. 9 par. 2-3].
Regarding claim 14, Sathe teaches a pharmaceutical composition comprising the modified SRL protein and a pharmaceutically acceptable diluent or excipient [pg. 9 par. 1].
Regarding claim 15, Sathe teaches a nucleic acid molecule encoding the modified SRL protein that can be a recombinant vector [pg. 10 par. 3].
Regarding claim 16, Sathe teaches a transformed host cell comprising the nucleic acid molecule [pg. 11 par. 1]. There is no evidence of record that the disclosed process of transformation compared to the claimed process of transfection leads to a different structure in the resulting cell product; in both cases, the result is a cell comprising the nucleic acid.
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Figure 2: Alignment of instant SEQ ID NO: 1 and the Sathe R105C and C76G modified SRL protein.
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.
Claims 1-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 10, 12, and 18-24 of copending Application No. 18/692,059 (reference application) as evidenced by the Martin and Hine A Dictionary of Biology “genetic engineering (recombinant DNA technology)” (2008; PTO-892). The comparison is being made to the amended ‘059 claims filed 14 Mar 2024. Although the claims at issue are not identical, they are not patentably distinct from each other. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
‘059 claims 3, 26 teaches SEQ ID NOs: 5 and 8, which are identical to instant SEQ ID NOs: 3 and 4 (see alignments below, these sequences have the genetic modifications of claims 2-8). Also, ‘059 claim 1 (and dependent claims) teach a recombinant lectin with a drug conjugated at the cysteine terminus (right side) and ‘059 claim 5 teaches that the lectin can be conjugated by a free thiol moiety, which is present on a cysteine. One of ordinary skill in the art would consider it obvious to achieve this by adding a C-terminal cysteine as shown in the sequences from ‘059 claims 3, 26 because the claims teach that this is a successful way to achieve the result. Oxford Reference teaches that recombinant DNA and proteins are made by “altering the characters of an organism by inserting genes from another organism into its DNA” (par. 1), so the teaching of a recombinant lectin also inherently teaches a recombinant polynucleotide encoding the protein and a cell (organism) comprising the recombinant polynucleotide. ‘059 claim 12 teaches that the protein drug can be formulated into a pharmaceutical composition and used for treatment and prevention of cancer.
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Figure 3: Alignment of instant SEQ ID NO: 3 and Sequence 5, US/18692059A.
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Figure 4: Alignment of instant SEQ ID NO: 4 and Sequence 8, US/18692059A.
Claims 1-8 and 11-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7, 9-10, and 13-15 of copending Application No. 19/130,824 (reference application). The comparison is being made to the amended ‘824 claims filed 16 May 2025. Although the claims at issue are not identical, they are not patentably distinct from each other. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
‘059 claim 7 teaches a recombinant plasmid encoding SEQ ID NOs: 13 and 16, which are identical to instant SEQ ID NOs: 3 and 4 (see alignments below, these sequences have the genetic modifications of claims 2-8 and the properties of claim 1 and 12-13). ‘059 claims 13-14 teach host cells comprising the plasmid. ‘059 claims 9-10 teach expressing and using the recombinant protein encoded in the plasmid and using it in cancer diagnosis or cancer therapy, and ‘059 claim 15 teaches a method of producing the protein of interest. For instant claims 11-13, the proteins are capable of use in these ways because it is the same sequences as disclosed in the specification as being capable of use in these ways.
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Figure 5: Alignment of instant SEQ ID NO: 3 and Sequence 13, US/19130824.
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Figure 6: Alignment of instant SEQ ID NO: 4 and Sequence 16, US/19130824.
Conclusion
No claims are allowed.
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/AMELIA NICOLE DICKENS/Examiner, Art Unit 1645
/DANIEL E KOLKER/Supervisory Patent Examiner, Art Unit 1645