DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Application, Amendments and/or Claims
The amendment of 06 June 2023 has been entered in full. Claims 1, 4, 15, 16-18, 21, 24, 28, 31, 33, 35, 37, 40, 41, 43, 47, and 48 are amended. Claims 2, 3, 5-14, 19, 20, 22, 23, 25-27, 29, 30, 34, 38, 39, 42, 44-46, 49, and 50 are cancelled.
Claims 1, 4, 15-18, 21, 24, 28, 31-33, 35-37, 40, 41, 43, 47, and 48 are under consideration in the instant application.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 13 January 2026 and 06 June 2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Specification
1. The disclosure is objected to because of the following informalities:
1a. The specification filed 06 June 2023 is missing page numbers on each page. Applicant is reminded that the pages of a specification must be numbered consecutively (see 37 CFR 1.52(b)(5); MPEP §608.01(I)).
1b. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see two hyperlinks in [00073]). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Appropriate correction is required.
Claim Objections
2. Claims 1, 4, 15-18, 28, 33, 43, and 47 are objected to because of the following informalities:
2a. In claim 1, line 1, after the phrase “antigen-binding protein”, the word “that” should be inserted. Alternatively, the word “comprises” could be amended to recite “comprising”.
2b. In claim 1, line 4, after the phrase “ID NO.: 2,”, the word “and” is missing and should be inserted.
2c. In claim 4, line 4, after the phrase “ID NO.: 5,”, the word “and” is missing and should be inserted.
2d. In claims 1, 4, and 15-18, each recitation of “an amino acid sequence” should be amended to recite “the amino acid sequence”.
2e. Claims 1, 4, and 15 recite the acronyms “HCDR” and “LCDR” without first defining what they represent. While the claims can reference acronyms, the material presented by the acronym must be clearly set forth at the first use of the acronym and/or in each independent claim.
2f. In claim 15, lines 3-6 (regarding specific HCDR sequences) are duplicative of the limitations recited in instant claim 1 and should be deleted.
2g. Claims 16-18 recite the acronyms “VH” and/or “VL” without first defining what they represent. While the claims can reference acronyms, the material presented by the acronym must be clearly set forth at the first use of the acronym and/or in each independent claim.
2h. In claims 16 and 17, line 2, after the phrase “claim 1, comprising”, the word “a” is missing and should be inserted.
2i. In claim 16, line 3, the plural word “sequences” should be amended to recite the singular, “sequence”.
2j. In claim 18, subparts (1)-(6) should be renumbered utilizing “(i)-(vi)” or “(a)-(gf” so as to prevent confusion with claim numbering.
2k. In claim 28, line 2, the phrase “which is able to specifically bind” should be simplified to recite “which binds” or “which specifically binds”.
2l. In claim 33, lines 2-3 recite the phrases “capable of inhibiting the enzymatic activity of CD73”, “capable of preventing or reducing the activation of CD73”, and “capable of inducing endocytosis” should be positive recitations. Please note that this issue could be overcome by amending claim 33 to recite, for example, “the isolated antigen-binding protein of claim 1, which inhibits the enzymatic activity of CD73, prevents or reduces the activation of CD73, and/or induces endocytosis of CD73 on a cell surface”.
2m. In claim 43, lines 1-2, after the phrase “and/or treating”, the word “a” is missing and should be inserted.
2n. In claim 47, line 2, the word “include” should be amended to recite “includes”.
Appropriate correction is required.
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.
3. Claims 33 and 48 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.
3a. Claim 33 recites the limitation "the cell surface" in line 4. There is insufficient antecedent basis for this limitation in the claim. Claim 1, from which claim 33 depends, does not recite “cell surface”. Please note that this issue could be overcome by amending claim 33 to recite “a cell surface”.
3b. Claim 48 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps/elements, such omission amounting to a gap between the steps/elements. See MPEP § 2172.01. Claim 48 recites a method for detecting CD73 in a sample, which includes the administration of the isolated antigen-binding protein of claim 1. However, is the isolated antigen-binding protein administered to a subject? Is it administered to a cell culture/sample?
Furthermore, there are no additional steps indicating how CD73 is actually detected in the sample. In other words, the claim does not recite a step(s) that clearly relate back to the preamble. For example, is a CD73-antigen binding protein complex formed? Is such complex detected by immunoassay? A flag tag? Fluorescence? Or, are some other entirely different steps/elements involved to detect CD73?
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.
4. Claims 1, 16, 21, 24, 28, 31-33, 35-37, 40, 41, 43, 47, and 48 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.
Claim 1 of the instant application recites an isolated antigen-binding protein comprises HCDR3, HCDR2 and HCDR1, wherein said HCDR3 comprises an amino acid sequence as set forth in SEQ ID No.: 3, wherein said HCDR2 comprises an amino acid sequence as set forth in SEQ ID No.: 2, wherein said HCDR1 comprises an amino acid sequence as set forth in SEQ ID No.: 1.
Instant claim 16 recites the isolated antigen-binding protein of claim 1, comprising VH, wherein said VH comprises an amino acid sequence set forth in SEQ ID No.: 29, SEQ ID No.: 31, SEQ ID No.: 33 or SEQ ID No.: 35.
The specification of the instant application teaches that CD73 is anchored to the cell surface by glycophosphatidylinositol (GPI) and exists mainly as a dimer ([0002]). The specification discloses that a large number of pre-clinical studies have shown that CD73 is abnormally overexpressed on a variety of tumor cells, including glioma, breast cancer, melanoma, non-small cell lung cancer, bladder cancer, ovarian cancer, and colorectal cancer, and that such upregulation is closely related to poor prognosis ([0003]). The specification states that there is currently no antibody or small molecule drug targeting human CD73 available on the market ([0004]). The specification teaches the generation of a human-murine CD73 antigen-binding protein comprising heavy chain variable region CDR1, CDR2, and CDR3 amino acid sequences of SEQ ID NOs: 1-3, respectively, and light chain variable region CDR1, CDR2, and CDR3 amino acid sequences of SEQ ID NOs: 4-6, respectively (“900581”; [000190-000192]; Table 2). The specification continues to teach that five humanized anti-CD73 antigen-binding proteins are generated and screened, each of which comprises the six CDRs of SEQ ID NOs: 1-6 ([000194]; see Examiner-generated Table below adapting the information from [000194]).
Antibody
VH SEQ ID NO
VL SEQ ID NO
900694
31
32
900695
33
34
900696
35
36
900697
33
36
900698
35
34
The specification teaches that antigen-binding proteins 900581 and 900694-900698 bind and inhibit CD73 (Examples 3-8). The specification also discloses that antigen-binding proteins 900581, 900697, and 900698 significantly inhibit the growth of MDA-MB-231 triple negative breast cancer cells in a mouse animal model (Example 10; Figure 9, “G4”). Similarly, the specification indicates that the antigen-binding protein 900698 significantly inhibits the growth of BxPC-3 pancreatic cancer cells in a mouse model (Example 11; Figure 10).
Regarding the instant claims, it is noted that claim 1 recites that the isolated antigen-binding protein comprises HCDR3, HCDR2, and HCDR1 amino acid sequences. Thus, the Examiner has interpreted the claimed antigen-binding protein as only comprising three specific CDRs (SEQ ID Nos.: 3, 2, and 1). However, it is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope (Paul, William E., Fundamental Immunology, 3rd Edition, Raven Press, New York, Chapt. 8, pp. 292-295 (1993), under the heading “Fv Structure and Diversity in Three Dimensions”;; see also Chiu et al. Antibodies 8: 55, doi:10.3390/antibod8040055, 2019 (page 4, section 1.2.2)). The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites (Paul, page 293, first column, lines 3-8 and line 31 to column 2, line 9 and lines 27-30). Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al. (Proc Natl Acad Sci USA. Vol 79, page 1979, 1982) and Zhang et al. (mAbs 7(1): 42-52, 2005; page 45, column 2)). Zhang et al. also indicate that minor variations in variable heavy and light chain CDR1s and CDR2s may lead to loss of antigen binding (page 46, column 1). Chiu et al. even teach that despite the obvious development in algorithms and computer power, the quality of antibody structure prediction remains inadequate and the results of antibody-antigen docketing are disappointing (page 11, 1st full paragraph). Chiu et al. acknowledge the advancement in antibody engineering, but note that it is still not possible to predict point mutations that improve affinity in both antibodies and multispecific molecules (page 51, lines 6-12). Thus, the state of the art recognized that it would be highly unpredictable that an antigen-binding protein comprising less than six CDRs from the variable heavy and light chains of an anti-CD73 antibody, would maintain its required conformation and would have the requisite antigen binding function.
The first paragraph of 35 U.S.C. § 112 "requires a 'written description of the invention' which is separate and distinct from the enablement requirement." Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563 (Fed. Cir. 1991). An adequate written description of a chemical invention "requires a precise definition, such as by structure, formula, chemical name, or physical properties." University of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916, 927 (Fed. Cir. 2004); Regents of the Univ. of Cal. v. Eli Lilly & Co., Inc., 119 F.3d 1559, 1566 (Fed. Cir. 1997); Fiers v. Revel, 984 F.2d 1164, 1171 (Fed. Cir. 1993). "A description of what a material does, rather than of what it is, usually does not suffice." Rochester, 358 F.3d at 923; Eli Lilly, 119 F.3d at 1568. Instead, the "disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter purportedly described." Id. In addition, possession of a genus "may be achieved by means of a recitation of a representative number of [compounds]... falling within the scope of the genus." Eli Lilly, 119 F.3d at 1569. Possession may not be shown by merely describing how to obtain possession of members of the claimed genus. See Rochester, 358 F.3d at 927.
Thus, case law dictates that to provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include actual reduction to practice, disclosure of drawings or structure chemical formulas, sufficient relevant identifying characteristics (such as, complete or partial structure, physical and/or chemical properties, and functional characteristics when coupled with a known or disclosed structure/function correlation), methods of making the claimed product, level of skill and knowledge in the art, predictability in the art, or any combination thereof. In the instant case, the factors present in the claims are (1) structural characteristics that the antigen-binding protein comprises HCDR3, HCDR2 and HCDR1, wherein said HCDR3 comprises an amino acid sequence as set forth in SEQ ID No.: 3, wherein said HCDR2 comprises an amino acid sequence as set forth in SEQ ID No.: 2, wherein said HCDR1 comprises an amino acid sequence as set forth in SEQ ID No.: 1 and (2) functional characteristics of binding to CD73, inhibiting the enzymatic activity of CD73, preventing/reducing the activation of CD73, and inducing endocytosis of CD73. There is no identification of any particular sequence or structure of the antigen-binding protein that must be conserved in order to provide the required functions of binding to CD73, inhibiting the enzymatic activity of CD73, preventing/reducing the activation of CD73, and inducing endocytosis of CD73. Thus, the claims are drawn to a genus of antigen-binding proteins that bind CD73, wherein the antigen-binding protein comprises less than 6 CDRs.
In this case, the specification fails to disclose and there is no art-recognized correlation between the structure of the genus of antigen-binding proteins and the functions of binding to CD73, inhibiting the enzymatic activity of CD73, preventing/reducing the activation of CD73, and inducing endocytosis of CD73. In other words, the specification does not teach the structure which results in an antigen-binding protein with the claimed required characteristics. The description of antigen-binding proteins 900581 and 900694-900698 that comprise full length variable heavy and light chains (and all 6 CDRs) of the instant specification is not adequate written description of an entire genus of antigen-binding proteins that bind CD73, inhibit the enzymatic activity of CD73, prevent/reduce the activation of CD73, and induce endocytosis of CD73, wherein the antigen-binding protein comprises less than 6 CDRs.
Applicant is reminded that generally, in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus (Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956 (Fed. Cir. 2002); Noelle v. Lederman, 355 F.3d 1343 (Fed. Cir. 2004); Regents of the University of California v. Eli Lilly Co., 119 F.3d 1559 (Fed. Cir. 1997)). A patentee must disclose “a representative number of species within the scope of the genus of structural features common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus” (see Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017) at page 1358). An adequate written description must contain enough information about the actual makeup of the claimed products – “a precise definition, such as structure, formula, chemic name, physical properties of other properties, of species falling with the genus sufficient to distinguish the gene from other materials”, which may be present in “functional terminology when the art has established a correlation between structure and function” (Amgen page 1361).
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed” (See page 1117). See also, Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017), relying upon Ariad Pharms., Inc. v. Eli Lily & Co., 94 USPQ2d 1161 (Fed Cir. 2010). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed” (See Vas-Cath at page 1116). A “mere wish or plan” to obtain the claimed invention is not sufficient (Centocor Orth Biotech, Inc. v. Abbott Labs, 636 F.3d 1341 (Fed. Cir. 2011); Regents of the Univ. of California, 119 F.3d at 1566). In the instant application, the skilled artisan cannot envision the detailed chemical structure of an anti-CD73 antigen-binding protein that comprises less than 6 CDRs of the encompassed claims, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The antigen-binding protein is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Therefore, only an antigen-binding protein comprising heavy chain variable region CDR1, CDR2, and CDR3 amino acid sequences of SEQ ID NOs: 1-3, respectively, and light chain variable region CDR1, CDR2, and CDR3 amino acid sequences of SEQ ID NOs: 4-6, respectively (and the corresponding heavy chain and light chain variable region sequences as recited in claim 18), but not the full breadth of the claims meets the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115). See also Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1355 (Fed. Cir. 2010).
5. Claims 1, 16, 21, 24, 28, 31-33, 35-37, 40, 41, 43, 47, and 48 are 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) an antigen-binding protein comprising heavy chain variable region CDR1, CDR2, and CDR3 amino acid sequences of SEQ ID NOs: 1-3, respectively, and light chain variable region CDR1, CDR2, and CDR3 amino acid sequences of SEQ ID NOs: 4-6, respectively (and corresponding heavy chain and light chain variable region sequences as recited in claim 18), does not reasonably provide enablement for an antigen-binding protein comprising heavy chain variable region CDR1, CDR2, and CDR3 amino acid sequences of SEQ ID NOs: 1-3, respectively. Furthermore, the specification, while being enabling for (B) a method of treating a cancer or tumor that overexpresses CD73 comprising administering to a subject in need thereof an antigen-binding protein comprising heavy chain variable region CDR1, CDR2, and CDR3 amino acid sequences of SEQ ID NOs: 1-3, respectively, and light chain variable region CDR1, CDR2, and CDR3 amino acid sequences of SEQ ID NOs: 4-6, respectively (and corresponding heavy chain and light chain variable region sequences as recited in claim 18) does not reasonably provide enablement for a method of preventing, relieving and/or treating disease and/or disorder, comprising administering to a subject in need thereof the isolated antigen-binding protein of claim 1, wherein said disease and/or disorder is a CD73-mediated disease and/or disorder. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Claim 1 of the instant application recites an isolated antigen-binding protein comprises HCDR3, HCDR2 and HCDR1, wherein said HCDR3 comprises an amino acid sequence as set forth in SEQ ID No.: 3, wherein said HCDR2 comprises an amino acid sequence as set forth in SEQ ID No.: 2, wherein said HCDR1 comprises an amino acid sequence as set forth in SEQ ID No.: 1.
Instant claim 16 recites the isolated antigen-binding protein of claim 1, comprising VH, wherein said VH comprises an amino acid sequence set forth in SEQ ID No.: 29, SEQ ID No.: 31, SEQ ID No.: 33 or SEQ ID No.: 35.
Claim 43 recites a method of preventing, relieving and/or treating disease and/or disorder, comprising administering to a subject in need thereof the isolated antigen-binding protein of claim 1, wherein said disease and/or disorder is a CD73-mediated disease and/or disorder.
The specification of the instant application teaches that CD73 is anchored to the cell surface by glycophosphatidylinositol (GPI) and exists mainly as a dimer ([0002]). The specification discloses that a large number of pre-clinical studies have shown that CD73 is abnormally overexpressed on a variety of tumor cells, including glioma, breast cancer, melanoma, non-small cell lung cancer, bladder cancer, ovarian cancer, and colorectal cancer, and that such upregulation is closely related to poor prognosis ([0003]). The specification states that there is currently no antibody or small molecule drug targeting human CD73 available on the market ([0004]). The specification teaches the generation of a human-murine CD73 antigen-binding protein comprising heavy chain variable region CDR1, CDR2, and CDR3 amino acid sequences of SEQ ID NOs: 1-3, respectively, and light chain variable region CDR1, CDR2, and CDR3 amino acid sequences of SEQ ID NOs: 4-6, respectively (“900581”; [000190-000192]; Table 2). The specification continues to teach that five humanized anti-CD73 antigen-binding proteins are generated and screened, each of which comprises the six CDRs of SEQ ID NOs: 1-6 ([000194]; see Examiner-generated Table below adapting the information from [000194]).
Antibody
VH SEQ ID NO
VL SEQ ID NO
900694
31
32
900695
33
34
900696
35
36
900697
33
36
900698
35
34
The specification teaches that antigen-binding proteins 900581 and 900694-900698 bind and inhibit CD73 (Examples 3-8). The specification also discloses that antigen-binding proteins 900581, 900697, and 900698 significantly inhibit the growth of MDA-MB-231 triple negative breast cancer cells in a mouse animal model (Example 10; Figure 9, “G4”). Similarly, the specification indicates that the antigen-binding protein 900698 significantly inhibits the growth of BxPC-3 pancreatic cancer cells in a mouse model (Example 11; Figure 10).
(i) Regarding the instant claims, it is noted that claim 1 recites that the isolated antigen-binding protein comprises HCDR3, HCDR2, and HCDR1 amino acid sequences. Thus, the Examiner has interpreted the claimed antigen-binding protein as only comprising three specific CDRs (SEQ ID Nos.: 3, 2, and 1). However, it is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope (Paul, William E., Fundamental Immunology, 3rd Edition, Raven Press, New York, Chapt. 8, pp. 292-295 (1993), under the heading “Fv Structure and Diversity in Three Dimensions”;; Chiu et al. Antibodies 8: 55, doi:10.3390/antibod8040055, 2019 (page 4, section 1.2.2)). The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites (Paul, page 293, first column, lines 3-8 and line 31 to column 2, line 9 and lines 27-30). Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al. (Proc Natl Acad Sci USA. Vol 79, page 1979, 1982) and Zhang et al. (mAbs 7(1): 42-52, 2005; page 45, column 2)). Rudikoff et al. teach that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function. Zhang et al. also indicate that minor variations in variable heavy and light chain CDR1s and CDR2s may lead to loss of antigen binding (page 46, column 1). Chiu et al. even teach that despite the obvious development in algorithms and computer power, the quality of antibody structure prediction remains inadequate and the results of antibody-antigen docketing are disappointing (page 11, 1st full paragraph). Chiu et al. acknowledge the advancement in antibody engineering, but note that it is still not possible to predict point mutations that improve affinity in both antibodies and multispecific molecules (page 51, lines 6-12). Thus, the state of the art recognized that it would be highly unpredictable that an antigen-binding protein comprising less than six CDRs from the variable heavy and light chains of an anti-CD73 antibody, would maintain its required conformation and would have the requisite antigen binding function. Thus, the minimal antigen-binding protein which the skilled artisan would consider predictive of the function of binding CD73 includes both heavy and light chain variable regions comprising all six CDRs (three from the heavy chain variable region and three from the light chain variable region) from a parental antibody in the context of framework sequences which maintain their correct spatial orientation.
The relevant art teaches that while CDR3 is important for antigen-binding, the conformations of other CDRs also influence binding. MacCallum et al. (J Mol Biol. 262: 732-745, 1996) analyzed many different antibodies for interactions with antigen and state that although CDR3 of the heavy and light chain dominate, a number of residues outside the standard CDR definitions make antigen contacts (see page 733, right column) and non-contacting residues within the CDRs coincide with residues as important in defining canonical backbone conformations (see page 735, left col). De Pascalis et al. (The Journal of Immunology. 169: 3076-3084, 2002) demonstrate that grafting of the CDRs into a human framework was performed by grafting CDR residues and maintaining framework residues that were deemed essential for preserving the structural integrity of the antigen binding site (see page 3079, right column). Although abbreviated CDR residues were used in the constructs, some residues in all 6 CDRs were used for the constructs (see page 3080, left column). The fact that not just one CDR is essential for antigen binding or maintaining the conformation of the antigen binding site is underscored by Casset et al. (Biochemical and Biophysical Research Communications 307: 198-205, 2003), who constructed a peptide mimetic of an anti-CD4 monoclonal antibody binding site by rational design and the peptide was designed with 27 residues formed by residues from 5 CDRs (see entire document). Casset et al. also teach that although CDR H3 is at the center of most if not all antigen interactions, clearly other CDRs play an important role in the recognition process (page 199, left column) and this is demonstrated in this work by using all CDRs except L2 and additionally using a framework residue located just before the H3 (see page 202, left column). Holm et al. (Mol Immunology. 44: 1075-1084, 2007) describe the mapping of an anti-cytokeratin antibody where although residues in the CDR3 of the heavy chain were involved in antigen binding, unexpectedly a residue in CDR2 of the light chain was also involved (abstract). Chen et al. (J Mol Biol. 293: 865-881, 1999) describe high affinity variant antibodies binding to VEGF wherein the results show that the antigen binding site is almost entirely composed of residues from heavy chain CDRs, CDR-H1, H2, H3 (page 866). Zhang et al. indicate that minor variations in variable heavy and light chain CDR1s and CDR2s of an anti-EphA2 scFv may lead to loss of antigen binding (page 46, column 1).
Thus, it is unlikely that an antigen-binding protein as recited in the claims, which comprises less than the full complement of specific CDRs, will have the required functionality of binding CD73, inhibiting the enzymatic activity of CD73, preventing/reducing the activation of CD73, and inducing endocytosis of CD73. The specification provides no direction or guidance regarding how to produce an antigen-binding protein that contains less than the full complement of CDRs from the heavy and light chain variable regions that binds CD73. Undue experimentation would be required to produce the invention commensurate with the scope of the claims from the specification alone. It is acknowledged that the level of skill of those in the art is high, but it is not disclosed and not predictable from the limited teachings of the prior art and specification how to make an antigen-binding protein that contains less than the full complement of CDRs from the heavy and light chain variable regions that binds CD73. The specification has not provided the person of ordinary skill in the art the guidance necessary to be able to make and use the claimed invention.
Due to the large quantity of experimentation necessary to determine how to make an antigen-binding protein that comprises less than the full complement of CDRs; the lack of direction/guidance presented in the specification regarding same; lack of working examples; the teachings of the prior art; the complex nature of the invention; and the unpredictability of the effects of CDR and heavy/light chain alterations on antibody activity, undue experimentation would be required of the skilled artisan to use the claimed invention.
(ii) Instant claim 43 broadly recites a method of preventing, relieving and/or treating disease or disorder, comprising administering to a subject in need thereof an antigen-binding protein comprising HCDR3, HCDR2 and HCDR1, wherein said HCDR3 comprises an amino acid sequence as set forth in SEQ ID No.: 3, wherein said HCDR2 comprises an amino acid sequence as set forth in SEQ ID No.: 2, wherein said HCDR1 comprises an amino acid sequence as set forth in SEQ ID No.: 1, wherein said disease and/or disorder is a CD73-mediated disease and/or disorder.
First, the instant specification does not provide a specific definition of the term “mediated” or “mediate” and thus, the Examiner has interpreted the phrase “CD73-mediated disease and/or disorder” as encompassing diseases/disorders that simply involve CD73 or are affected by or as a result of CD73. So, in other words, “CD73-mediated disease and/or disorder” can encompass diseases or disorders that not only have increased CD73 signaling/expression, but also decreased CD73 signaling/expression. Second, there are no methods or working examples in the instant specification that indicate all possible CD73-mediated diseases or disorders are amenable to treatment with an antigen-binding protein that binds CD73. A large quantity of experimentation would be required of the skilled artisan to determine if an antigen-binding protein that binds CD73 prevents, relieves, and/or treats all possible diseases or disorders “mediated by CD73”. Such experimentation is considered undue.
The specification discloses that antigen-binding proteins 900581, 900697, and 900698 significantly inhibit the growth of MDA-MB-231 triple negative breast cancer cells in a mouse animal model (Example 10; Figure 9, “G4”). Similarly, the specification indicates that the antigen-binding protein 900698 significantly inhibits the growth of BxPC-3 pancreatic cancer cells in a mouse model (Example 11; Figure 10). Relevant literature teaches that CD73 is involved in immune suppression, tumor growth, metastasis, angiogenesis, and drug resistance (Bach et al. In J Mol Sci 24: 11759, 2023;; page 4, section 2.3; page 6, section 2.5). Bi et al. (J Med Chem 68: 6860-6869, 2025) disclose that CD73 has higher expression in many tumor specimens, leading to the targeting of CD73 across different cancer types, such as bladder cancer, lung cancer, breast cancer, gall bladder cancer, gastrointestinal cancer, colorectal cancer, prostate cancer, head and neck squamous cell carcinoma, pancreatic ductal adenocarcinoma, melanoma, glioblastoma, and chronic lymphocytic leukemia (page 6860, column 2; page 6865, Table 1). See also Bach et al., Table 1 and pages 8-12.
Conversely, the state of the art also discloses that CD73 regulates autoimmune diseases and serves as a checkpoint in inflammation (Yang et al., Curr Med Chem 25: 2260-2271, 2018; page 2261, top of column 2). For example, CD73 regulates vascular permeability and protects endothelial barrier during inflammation (Yang et al., page 2261, column 2, last paragraph). Yang et al. teach that in CD73 knockout mice, severity of inflammatory bowel disease (IBD) and rheumatoid arthritis is increased (pages 2262-2263, sections 4.2.1 and 4.2.2). CD73 deficiency in either allogeneic transplantation donor or recipient mice results in decreased allograft survival (page 2263, section 4.2.4). Yang et al. indicate that CD73 protects organs from ischemia-reperfusion injury (page 2263, section 4.3.1).
Therefore, the skilled artisan would not be able to predict that the findings of the instant specification would extend to such broad functions as recited in claim 43. In fact, the skilled artisan would predict that administration of an antigen-binding protein against CD73 (as claimed) would actually exacerbate some diseases and disorders mediated by CD73, such as IBD, rheumatoid arthritis, allograft transplantation, and ischemia-reperfusion injury.
Lastly, in view of the lack of a definition of the term “prevent” or “preventing” in the instant specification, the term “preventing” as recited in instant claim 43 is interpreted by the Examiner as meaning that an activity is suppressed or will not occur, i.e. a CD73-mediated disease or disorder will not occur. However, the specification and prior art do not teach any methods or working examples that indicate prevention of all possible CD73-mediated diseases or disorders by administration of an antigen-binding protein that binds CD73. At the time of filing the instant application, one skilled in the art would also not be able to predict administration of an antigen-binding protein that binds CD73 would prevent all possible CD73-mediated diseases or disorders, particularly in view of the teachings of Yang et al. The prior art also discloses that cancer prevention is complex and has had limited success (White et al., J Adolescent Health 52: S1-S7, 2013; page S2; page S5, column 1, 2nd full paragraph). White et al. teach that cancer is the result of multiple alterations in processes that control cell proliferation, invasion, and spread (page S2, column 1, 1st full paragraph). White et al. continue to disclose that nearly all cancers result from multiple factors that influence these processes over an extended time, such factors including genetic mutations, environmental interactions, and lifestyle (page S2, column 1, 1st full paragraph). Thus, undue experimentation would be required of the skilled artisan to determine the optimal quantity and duration of administration of an antigen-binding protein that binds CD73 for prevention of all possible CD73-mediated diseases and disorders. The limited teachings of the specification are not adequate guidance, but are merely an invitation for the artisan to use the current invention as a starting point for further experimentation.
Applicant is reminded that the courts have stated that patent protection is granted in return for an enabling disclosure, not for vague intimations of general ideas that may or may not be patentable. Tossing out the mere germ of an idea does not constitute an enabling disclosure. Reasonable detail must be provided in order to enable members of the public to understand and carry out the invention. See Genentech v. Novo Nordisk A/S (CAFC) 42 USPQ2d 1001 (1997). Furthermore, Applicant is reminded that a single embodiment may provide broad enablement in cases involving predictable factors such as mechanical or electrical elements, but more will be required in cases that involve unpredictable factors such as most chemical reactions and physiological activity. See In re Vickers, 141 F.2d 522, 526-27, 61 USPQ 122, 127 (CCPA 1944); In re Cook, 439 F.2d 730, 734, 169 USPQ 298, 301 (CCPA 1971); In re Soll, 97 F.2d 623, 634, 38 USPQ 189, 191 (CCPA 1938; In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970); In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); In re Vaeck, 947 F.2d 488, 496, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991).
In summary, in view of the disclosure of the instant specification and the relevant literature, the specification is only enabling for a method of treating a cancer or tumor that overexpresses CD73 comprising administering to a subject in need thereof an antigen-binding protein comprising heavy chain variable region CDR1, CDR2, and CDR3 amino acid sequences of SEQ ID NOs: 1-3, respectively, and light chain variable region CDR1, CDR2, and CDR3 amino acid sequences of SEQ ID NOs: 4-6, respectively (and corresponding heavy chain and light chain variable region sequences as recited in claim 18).
Due to the large quantity of experimentation necessary to treat and prevent all possible CD73-mediated diseases or disorders by administration of an antigen-binding protein that binds CD73; the lack of direction/guidance presented in the specification regarding the same; the absence of working examples directed to the same; the complex nature of the invention; the state of the art (see Bach et al., Bi et al., Yang et al., and White et al.); the unpredictability of treating and preventing all possible CD73-mediated diseases or disorders; and the breadth of the claims, undue experimentation would be required of the skilled artisan to make and/or use the claimed invention.
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.
6. Claims 1, 4, 15, 16-18, 21, 24, 28, 31-33, 35, 36, 40, 41, 43, and 47 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 16-19, 32, 33, 36, 37, 39, 42-47, 54, 57, 59, and 60 of copending Application No. 18/847,043. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to the same antigen-binding protein that binds CD73.
Claim 1 of the instant application recites an isolated antigen-binding protein comprises HCDR3, HCDR2 and HCDR1, wherein said HCDR3 comprises an amino acid sequence as set forth in SEQ ID No.: 3, wherein said HCDR2 comprises an amino acid sequence as set forth in SEQ ID No.: 2, wherein said HCDR1 comprises an amino acid sequence as set forth in SEQ ID No.: 1.
Instant claim 4 recites that the antigen-binding protein comprises LCDR3, LCDR2, and LCDR1, wherein said LCDR3 comprises an amino acid sequence as set forth in SEQ ID No.: 6, wherein said LCDR3 comprises an amino acid sequence as set forth in SEQ ID No.: 5, wherein said LCDR1 comprises an amino acid sequence as set forth in SEQ ID No.: 4.
Meanwhile, claim 1 of the ’043 application recites an antibody-drug conjugate, comprising a CD73-targeting antibody or antigen-binding fragment thereof, wherein the CD73-targeting antibody or the antigen binding fragment thereof comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1 comprises the amino acid sequence as set forth in SEQ ID NO: 1, the HCDR2 comprises the amino acid sequence as set forth in SEQ ID NO: 2, the HCDR3 comprises the amino acid sequence as set forth in SEQ ID NO: 3, the LCDR1 comprises the amino acid sequence as set forth in SEQ ID NO: 4, the LCDR2 comprises the amino acid sequence as set forth in SEQ ID NO: 5, and the LCDR3 comprises the amino acid sequence as set forth in SEQ ID NO: 6.
It is noted that the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 amino acid sequences of SEQ ID NOs: 1-6 of the instant application are 100% identical to the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 amino acid sequences of SEQ ID NOs: 1-6 of the ‘043 application.
The VH amino acid sequences of SEQ ID NOs: 29, 31, 33, and 35 of instant claims 16 and 18 are also 100% identical to the VH amino acid sequences of SEQ ID NOs: 29, 31, 33, and 35 of claims 16 and 18 of the ‘043 application.
The VL amino acid sequences of SEQ ID NOs: 30, 32, 34, and 36 of instant claims 17 and 18 are also 100% identical to the VL amino acid sequences of SEQ ID NOs: 30, 32, 34, and 36 of claims 17 and 18of the ‘043 application.
Claim 41 of the instant application and claim 54 of the ‘043 application recite a pharmaceutical composition.
Claim 43 of the instant application recites a method of preventing, relieving and/or treating disease and/or disorder, comprising administering to a subject in need thereof the isolated antigen-binding protein of claim 1, wherein said disease and/or disorder is a CD73-mediated disease and/or disorder. Meanwhile, claim 57 of the ‘043 application recites a method of preventing or treating tumors comprising administering to a subject in need thereof the antibody-drug conjugate according to claim 1, wherein the tumor comprises a solid tumor and/or a non-solid tumor.
Claim 47 of the instant application and claim 60 of the ‘043 application recite that the disease/tumor treated is breast cancer.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
7. Claims 1, 4, 15-18, 21, 24, 28, 31-33, 35-37, 40, 41, and 43 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 6, 15, 23, 52, 53, 71, 74, 78, 81, 100-105, 107, 115, and 116 of copending Application No. 18/872,227. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to the same antigen-binding protein that binds CD73.
Claim 1 of the instant application recites an isolated antigen-binding protein comprises HCDR3, HCDR2 and HCDR1, wherein said HCDR3 comprises an amino acid sequence as set forth in SEQ ID No.: 3, wherein said HCDR2 comprises an amino acid sequence as set forth in SEQ ID No.: 2, wherein said HCDR1 comprises an amino acid sequence as set forth in SEQ ID No.: 1.
Instant claim 4 recites that the antigen-binding protein comprises LCDR3, LCDR2, and LCDR1, wherein said LCDR3 comprises an amino acid sequence as set forth in SEQ ID No.: 6, wherein said LCDR3 comprises an amino acid sequence as set forth in SEQ ID No.: 5, wherein said LCDR1 comprises an amino acid sequence as set forth in SEQ ID No.: 4.
Meanwhile, claim 1 of the ’227 application, for example, recites an isolated antigen-binding protein, comprising a first binding domain and a second binding domain, wherein said first binding domain is capable of binding to a CD39 protein, and said second binding domain is capable of binding to a CD73 protein; and wherein said first binding domain comprises CDR1-3, said CDR1 comprises an amino acid sequence as set forth in SEQ ID NO: 3, said CDR2 comprises an amino acid sequence as set forth in SEQ ID NO: 2, and said CDR3 comprises an amino acid sequence as set forth in SEQ ID NO: 1. Claim 23 of the ‘227 application recites that said second binding domain comprises HCDR1-3 and LCDR1-3, and said HCDR1-3 and LCDR1-3 comprise amino acid sequences selected from the group consisting of:
(i) said HCDR1 comprising an amino acid sequence of SEQ ID NO: 11, said HCDR2 comprising an amino acid sequence as set forth in SEQ ID NO: 10, and-said HCDR3 comprising an amino acid sequence as set forth in SEQ ID NO: 9, said LCDR1 comprising an amino acid sequence as set forth in SEQ ID NO: 19, said LCDR2 comprising an amino acid sequence as set forth in SEQ ID NO: 18 (WAS), and said LCDR3 comprising an amino acid sequence as set forth in SEQ ID NO: 17; and
(ii) said HCDR1 comprising an amino acid sequence as set forth in SEQ ID NO: 29, said HCDR2comprising an amino acid sequence as set forth in SEQ ID NO: 28, and said HCDR3 comprising an amino acid sequence as set forth in SEQ ID NO: 27, said LCDR1 comprising an amino acid sequence as set forth in SEQ ID NO: 36, said LCDR2 comprising an amino acid sequence as set forth in SEQ ID NO: 35 (LAS), and said LCDR3 comprising an amino acid sequence as set forth in SEQ ID NO: 34.
It is noted that the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 amino acid sequences of SEQ ID NOs: 1-6 of the instant application are 100% identical to the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 amino acid sequences of SEQ ID NOs: 11, 10, 9, 19, 18, and 17, respectively, of the ‘227 application.
The VH amino acid sequence of SEQ ID NO: 35 of instant claims 16 and 18 is also 100% identical to the VH amino acid sequence of SEQ ID NO: 16 of claims 52 and 100 of the ‘227 application (see sequence alignment below with CDRs underlined).
Sequence 16, US/18872227
Publication No. US20250361314A1
GENERAL INFORMATION
TITLE OF INVENTION: CD39/CD73 BISPECIFIC ANTIGEN BINDING PROTEIN AND USE THEREOF TECHNICAL FIELD (en)
FILE REFERENCE: 0211-PA-020US
CURRENT APPLICATION NUMBER: US/18/872,227
CURRENT FILING DATE: 2024-12-05
NUMBER OF SEQ ID NOS: 49
SEQ ID NO 16
LENGTH: 125
TYPE: PRT
FEATURE:
NAME/KEY: REGION
LOCATION: 1..125
QUALIFIERS: note = 900698 VH
FEATURE:
NAME/KEY: source
LOCATION: 1..125
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 100.0%; Score 659; Length 125;
Best Local Similarity 100.0%;
Matches 125; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVESGGGLVKPGGSLRLSCAASGFTFSKYAMSWIRQAPGKGLEWVAEISSGGGYINY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVESGGGLVKPGGSLRLSCAASGFTFSKYAMSWIRQAPGKGLEWVAEISSGGGYINY 60
Qy 61 ADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARAIYYYGSSYNYYAMDYWGQGTT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARAIYYYGSSYNYYAMDYWGQGTT 120
Qy 121 VTVSS 125
|||||
Db 121 VTVSS 125
The VL amino acid sequence of SEQ ID NO: 34 of instant claims 17 and 18 is also 100% identical to the VL amino acid sequence of SEQ ID NO: 24 of claims 52 and 100 of the ‘227 application (see sequence alignment below with CDRs underlined).
Sequence 24, US/18872227
Publication No. US20250361314A1
GENERAL INFORMATION
TITLE OF INVENTION: CD39/CD73 BISPECIFIC ANTIGEN BINDING PROTEIN AND USE THEREOF TECHNICAL FIELD (en)
FILE REFERENCE: 0211-PA-020US
CURRENT APPLICATION NUMBER: US/18/872,227
CURRENT FILING DATE: 2024-12-05
NUMBER OF SEQ ID NOS: 49
SEQ ID NO 24
LENGTH: 107
TYPE: PRT
FEATURE:
NAME/KEY: REGION
LOCATION: 1..107
QUALIFIERS: note = 900698 VL
FEATURE:
NAME/KEY: source
LOCATION: 1..107
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 100.0%; Score 562; Length 107;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCRASQDVGTAEAWYQQKPGKAPKLLIYWASTRHTGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSLSASVGDRVTITCRASQDVGTAEAWYQQKPGKAPKLLIYWASTRHTGVPS 60
Qy 61 RFSGSGSGTDFTLTISSLQPEDFATYYCQQYSSYPLTFGQGTKLEIK 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDFTLTISSLQPEDFATYYCQQYSSYPLTFGQGTKLEIK 107
Claim 41 of the instant application and claim 71 of the ‘227 application recite a pharmaceutical composition.
Instant claim 37 recites an isolated nucleic acid encoding the antigen-binding protein and claim 102 of the ‘227 application recites one or more nucleic acid molecules encoding the isolated antigen-binding protein.
Claim 43 of the instant application recites a method of preventing, relieving and/or treating disease and/or disorder, comprising administering to a subject in need thereof the isolated antigen-binding protein of claim 1, wherein said disease and/or disorder is a CD73-mediated disease and/or disorder. Meanwhile, claim 107 of the ‘227 application recites a method of preventing or treating diseases and/or disorders comprising administering to a subject in need thereof the antigen-binding protein of claim 1.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowable.
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BEB
Art Unit 1647
29 April 2026
/BRIDGET E BUNNER/Primary Examiner, Art Unit 1647
Prosecution Insights