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 .
DETAILED ACTION
Status of the Claims
1. Claims 1-57 are the original claims filed on 3/23/2023. In the preliminary amendment of 11/9/2023, claims 20-21, 23, 25-26, 29, 31-35, 37-38, 40, 49-51, and 53 are amended, claims 1-19, 27, 28, 39, 41, 44-48, 52, and 57 are cancelled, and new claims 58-59 are added. Claims 20-26, 29-38, 40, 42-43, 49-51, 53-56, and 58-59 are pending.
Priority
2. USAN 18/028,170, filed 03/23/2023, is a National Stage entry of PCT/US2021/052446, International Filing Date: 09/28/2021, PCT/US2021/ 052446 is a Continuation of PCT/US21/43784, filed 07/29/2021, PCT/US2021/ 052446 is a Continuation of PCT/US21/35542, filed 06/02/2021, PCT/US21/35542 Claims Priority from Provisional Application 63/084,474, filed 09/28/2020.
Priority is granted to 63/084,474, filed 09/28/2020, for the claimed invention.
Information Disclosure Statement
3. As of 12/5/2025, a total of one (1) IDS if filed: 11/09/2023. The corresponding initialed and dated 1449 form is considered and of record.
Reference #9 on p. 7 of the 1449 form for the name of the patentee or applicant is amended to replace Dorken et al. with Micromet Ag.
Objections
Drawings
4. The drawing sheets for Figures 9, 43 and 47-48 are objected to because of the use of the term Octet, which is a trade name or a mark used in commerce, has been noted.
The drawing sheets for Figures 4, 16, 53E, 53F, and 53G are objected to because of the use of the term Avastin, which is a trade name or a mark used in commerce, has been noted.
The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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
5. The abstract of the disclosure is objected to because it uses the term “e.g.” much less being contained within parentheses. The POSA cannot ascertain whether the text is exemplary or descriptive of the invention. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
6. The disclosure is objected to because of the following informalities:
a) The use of the term, Octet, Alexa, Sepharose, Avastin (also see the sequence table under “description”), ForteBio, EZ-LINK, NOVOCYTE, TrypLE, GELTREX, NOVOEXPRESS, DNASTAR, MUSCLE, nanobody, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
b) The specification contains peptides > 4 amino acids in length that are required to be identified by SEQ ID NO pursuant to 37 CFR 1.821-1.825. See [0315-0319].
c) The specification contains a misspelling “Afibercept” for what should be Aflibercept.
Appropriate correction is required.
Claim Objections
7. Claims 23, 33, 35-38, 40, 42-43, 49-51, 53-56 and 59 are objected to because of the following informalities:
a) Amend claim 23 to recite “wherein the antibody moiety has an Fc fragment [is] selected from the group consisting of Fc fragments from IgG, IgA, IgD, IgE, IgM, and combinations and hybrids thereof.”
b) Amend claim 33 to recite “wherein the two heavy chains fused with the second moiety each comprise[s] the amino acid sequence set forth in SEQ ID NO: 342 or 366.”
c) Amend claims 35-37 to recite “nucleic acid molecule”. See [0123] of the specification.
d) Amend claim 38 to recite “
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
8. Claims 21-26 and 37 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.
a) Claims 21-26 recite the limitation "the antibody moiety". There is insufficient antecedent basis for this limitation in the claim. Claim 20 from which Claims 21-26 depend is not drawn to an antibody moiety.
b) Claim 37 is indefinite for failing to conclude with a period. The POSA cannot reasonably ascertain the metes and bounds of the claimed subject matter.
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.
Scope of Enablement
9. Claims 40, 42-43, 49-51, 53-56 and 59 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 the use of the monospecific 17B10 anti-CD93 antibodies and the bispecific 7F3 (anti-CD93) /Aflibercept (anti-VEGF) antibodies in treating (therapeutic, not prophylactic) cancers, does not reasonably provide enablement for the monospecific anti-CD93 antibodies or the bispecific anti-CD93 x anti-VEGF antibodies for treating and preventing just any condition 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 use the invention commensurate in scope with the claims.
Factors to be considered in determining whether undue experimentation is required, are summarized in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). They include the nature of the invention, the state of the prior art, the relative skill of those in the art, the amount of direction or guidance disclosed in the specification, the presence or absence of working examples, the predictability of the art, the breadth of the claims, the quantity of experimentation which would be required in order to practice the invention as claimed.
Claim interpretation
The broadest reasonable interpretation is using the anti-CD93 antibody of claim 40 or the bispecific CD93 (anti-CD93 x anti-VEGF) of claim 59 to treat any disease or condition in an individual, including for example, addiction, Parkinson’s disease, ALS, Bell’s Palsy, Epilepsy, heart disease, cirrhosis, etc.
CD93 is a C-type lectin transmembrane receptor which plays a role not only in cell-cell adhesion processes but also in host defense. CD93 was initially thought to be a receptor for C1q, but now is thought to instead be involved in intercellular adhesion and in the clearance of apoptotic cells [0004].
“treatment”: the specification is unequivocal that treatment encompasses prevention at
[0166] As used herein, “treatment” or “treating” is an approach for obtaining beneficial or desired results, including clinical results. For purposes of this application, beneficial or desired clinical results include, but are not limited to, one or more of the following: alleviating one or more symptoms resulting from the disease, diminishing the extent of the disease, stabilizing the disease (e.g., preventing or delaying the worsening of the disease), preventing or delaying the spread (e.g., metastasis) of the disease, preventing or delaying the recurrence of the disease, delaying or slowing the progression of the disease, ameliorating the disease state, providing a remission (partial or total) of the disease, decreasing the dose of one or more other medications required to treat the disease, delaying the progression of the disease, increasing or improving the quality of life, increasing weight gain, and/or prolonging survival. Also encompassed by “treatment” is a reduction of pathological consequence of cancer (such as, for example, tumor volume). The methods of the application contemplate any one or more of these aspects of treatment.
[0170] As used herein, “delaying development of a disease” means to defer, hinder, slow, retard, stabilize, suppress and/or postpone development of the disease (such as cancer). This delay can be of varying lengths of time, depending on the history of the disease and/or individual being treated. As is evident to one skilled in the art, a sufficient or significant delay can, in effect, encompass prevention, in that the individual does not develop the disease. For example, a late stage cancer, such as development of metastasis, may be delayed.
Claim 40 recites a method of treating a disease or condition comprising the step of administering to an individual an effective amount of the anti-CD93 antibody of claim 20. Claims 42-43 and 49 further limits the method of claim 40, wherein the disease or condition is any type of cancer, a solid tumor, and a species of cancer, respectively. Claims 50-51 and 53-56 depend from claim 40, do not limit the disease or disorder, and define the route of administration (claim 50); administering a second therapy (Claim 51); and the description of the second therapy (Claims 53-56).
Claim 59 recites a method of treating a disease or condition comprising the step of administering to an individual an effective amount of an anti-CD93 construct of claim 30 comprising an antibody comprising a first moiety that binds CD93 (7F3 (anti-CD93; clone VH/VL CDR1-3) and a second moiety that binds VEGF. The VEGF binding moiety is undefined in the claims by amino acid or nucleotide sequence thus the scope is unlimited.
Disclosure in the Specification
A) As regards the invention of monospecific antibody in method claims 40, 42-43, 49-51, and 53-56.
The specification teaches the anti-CD93 antibodies of the invention block the interaction, in vitro, of CD93 with IGFBP7 ([0061]; Example 5 at [0615-0616]); the interaction of CD93 with MMRN2 ([0062]; Example 6 at [0617-0620]); and HUVEC tube formation (Example 7 at [0621-0622]).
The 17B10 anti-CD93 antibodies are tested a syngeneic melanoma mouse model in Example 11 at [0632-0633]: a Lewis Lung carcinoma in Example 11 at [0634-0636]; a KI melanoma model Example 19 at [0674-0678], for example:
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The specification does NOT support or enable the use of the inventive anti-CD93 antibodies for use in the prevention of just any disease or condition much less any cancer.
The specification supports and enables the use the anti-CD93 antibodies, preferably, the 17B10 anti-CD93 antibodies, in treating cancer as a therapeutic modality.
The scope of the claims must bear a reasonable correlation with the scope of enablement. See In re Fisher, 166 USPQ 19, 24 (CCPA 1970). "[T]o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation.'" Genentech, Inc. v. Novo Nordisk, A/S, 108 F.3d 1361, 1365 (Fed. Cir. 1997) (quoting In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993)).
The Patent Act requires that patent applicant describes the invention in explicit terms to enable any person skilled in the art to make and use the invention. 35 U.S.C. 112. Applicants seek the coverage of incalculable diseases and disorders that are not claimed as being correlated with CD93 expression in any individual, in vivo, much less insofar as the claimed anti-CD93 antibodies having both a therapeutic and prophylactic affect, in vivo, on the disease or condition.
The enablement requirement is a crucial aspect of the patent “bargain”: an inventor is granted limited protection from competition in exchange for publicly disclosing their new technology. See the decision in Morse, Incandescent Lamp, and Holland Furniture, establishing the requirement that if a patent claims an entire class or genus of processes, machines, or compositions of matter, the specification must enable a person skilled in the field to make and use the entire class. If a patent claims an entire class of processes, machines, manufactures, or compositions of matter, the patent’s specification must enable a person skilled in the art to make and use the entire class. In other words, the specification must enable the full scope of the invention as defined by its claims. The more one claims, the more one must enable. See §112(a); see also Continental Paper Bag Co. v. Eastern Paper Bag Co., 210 U. S. 405 (1908) (“[T]he claims measure the invention.”).
B) As regards the invention of bispecific antibody in method claim 59 that depends from product claim 30.
The specification discloses the 7F3 (anti-CD93; clone VH/VL CDR1-3)/ Aflibercept (anti-VEGF) bispecific is effective as a therapeutic in treating cancer:
[0090] FIG. 52C shows the results of in vivo anti-tumor efficacy of 7F3, 16E4, 17B10 and 7F3/VEGFRFc in B16F10 mouse model as well as the body weight change of the treated mice. [0090] FIG. 53A shows the schematic design of h7F3/VEGFR constructs.
[0091] FIG. 53B shows the results of FACS binding assay between CD93 and chimeric 7F3- hIgG1 or an exemplary chimeric 7F3/VEGFR construct (i.e., 7F3-Aflibercept).
[0092] FIG. 53C-53D show the results of FACS blocking assay. FIG.53C shows that original 7F3-mIgG1, humanized 7F3-hIgG1 and the exemplary 7F3/VEGFR construct humanized 7F3- Aflibercept all block the interaction between CD93 and IGFBP7. FIG.53D shows that original 7F3-mIgG1, humanized 7F3-hIgG1 and the exemplary 7F3/VEGFR construct humanized 7F3- Aflibercept all block the interaction between CD93 and MMRN2.
[0093] FIG. 53E-F show the results of ELISA binding assay. FIG. 53E shows that chimeric 7F3-hIgG1 and humanized 7F3-Aflibercept both bind to human CD93 while humanized 7F3- Aflibercept and Avastin both bind to VEGFA. FIG. 53F shows that chimeric 7F3-hIgGl, chimeric 7F3-Aflibercept, and humanized 7F3-Aflibercept bind to both human CD93 and cynoCD93. Avastin, chimeric 7F3-Aflibercept and humanized 7F3-Aflibercept all bind to human VEGFA, while only chimeric 7F3-Aflibercept and humanized 7F3-Aflibercept bind to mouse VEGFA.
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The specification does NOT support or enable the use of the full scope of the inventive anti-CD93 (clone 7F3; VH/VL CDR1-3) x anti-VEGF antibody for use in the treatment (therapeutic) or prevention (prophylactic) of just any disease or condition much less any cancer.
The specification supports and enables the use the bispecific antibody anti-CD93 (clone 7F3; VH/VL CDR1-3) x anti-VEGF (Aflibercept) in treating cancer. The scope of the VEGF antibodies alone and in combination with any inventive amtiCD93 antibody much less clone 7F3 exceeds the scope of what is described in the specification for use in the treatment of any disease or condition.
The scope of the claims must bear a reasonable correlation with the scope of enablement. See In re Fisher, 166 USPQ 19 24 (CCPA 1970). Without such guidance, the amount of in vitro and in vivo animal model testing for any given much less the combination of antibodies, is unpredictable and the experimentation left to those skilled in the art is unnecessarily and improperly extensive and undue. See Amgen, Inc. v. Chugai Pharmaceutical Co. Ltd., 927 F,2d 1200, 18 USPQ 1016 (Fed. Cir. 1991) at 18 USPQ 1026 1027 and Ex parte Forman, 230 USPQ 546 (BPAI 1986).
Status of the Art for Immunotherapeutic Antibodies
Even assuming, arguendo, claim 59 is drawn to a cancer/tumor, the use of antibody immunotherapy for the treatment of tumors has been shown to have limitations. Five (5) art references spanning over 25 years in the field of immunotherapeutics and recognizing the complexity of antibody delivery to tumors in vivo are Fujimori et al. (J. Nuc. Med. 31:1191-1198 (1990)); Beckman et al. (Can. 109:170-179 (2007)); Thurber et al. (Adv. Drug Deliv. Rev. 60:1421-1434 (2008)); Rudnick et al. (Can. Biotherp. & Radiopharm. 24: 155-162 (2009)); and Huang et al. (Appl Microbiol Biotechnol (2010) 87:401–410).
Fujimori teaches for further understanding of Mab distribution in the tumor, one must consider as well the microscopic pharmacology: transport across the capillary wall, transport in tumor interstitium, cellular binding and metabolism. Fujimori discusses predictive models for accessing tumor antigen availability by Mab to examine the relationship between affinity and distribution. Fujimori teaches on p. 1196, Col. 2, ¶1:
“One strategy to overcome the binding-site barrier would be to increase the initial Mab dose. Even though Mab concentration in tumor does not always increase linearly as initial Mab concentration increases, a high initial plasma concentration leads to better percolation and results in more uniform distribution in tumor. Increasing Mab dose, however, decreases the specificity ratio and may cause toxicity or other side effects. For each Mab species and set of circumstances, there is an inherent balance of factors. Other causes of heterogeneous distribution include the functional and anatomical heterogeneity of tumors and their vessels..., and the elevated interstitial tissues…”
Beckman teaches on p. 175, Col. 2, ¶2-4:
“Optimizing biodistribution properties of Ab constructs depends on a large number of host and tumor variables. These include: the density and distribution of target Ag in tumors and normal tissues: the degree of target occupancy and residence tiemr equired for tumor cell kill; possible toxicities from normal tissue distribution; tumor size and vascularity; tumor interstitial pressure, convection and diffusion; and metabolism and internilzation rates for Ab-Ag constructs.
An equally large number of Ab construct and therapy variables are available for optimization, including size, charge, and valence; constant region type and glycosylation pattern; presence or absence of a radioisotope or a toxic moiety; dose, route, and schedule of administration; and use of a traditional or a pretargeting strategy. Given the complexity of the problem, systematic preclinical programs may enhance the likelihood of success in subsequent clinical studies. Such preclinical investigations should integrate both experimental and theoretical approaches.
Preclinical studies of a putative Ab-based therapeutic agent can encompass a variety of constructs, differing in molecular weight, affinity, valence, and/or other features of interest, which bind to the same epitope as demonstrated by competition experiments. The Ag density and target affinities should be known for both tumor cells and cross-reacting normal tissues, and the percent target occupancy and required residence time for tumor cell kill should ideally be investigated in vitro. Similarly, rate constants for Ab-Ag internalization should be determined, if applicable. Dose and schedule should be varied and antitumor efficacy, pharmacokinetics, overall biodistribution, homogeneity of intratumoral distribution, and tumor microvessel density and distribution ideally should be measured in tumor-bearing animals with a variety of tumor sizes.”
Studies in tumor-bearing rodents are often confounded by lack of normal tissue reactivity with Ab constructs directed toward human Ags, but studies in transgenic animal can be performed in some instances to alleviate this issue.”
Thurber teaches on p. 1431, Col 2, ¶3:
“Analyzing the fundamental rates that determine antibody uptake and distribution provides a theoretical framework for understanding and interpreting targeting experiments and improving on the limitations of uptake. It also provides a background for a more rational design of in vitro experiments, animal studies, and clinical trials. The insight gained from this type of modeling has multiple implications for imaging and therapy. For example, not all cells are exposed to the “average” concentration obtained in a tumor. A significant portion of cells can survive even if the tumor-averaged concentration is well above the LD50 in vitro. Also, the concentration that cells in a solid tumor are exposed to ([Ab]surf) is well below the plasma concentration. This means that the bulk antibody concentration in an in vitro spheroid experiment is not analogous to the plasma concentration but is actually well below it; large doses are required to overcome this poor extravasation. Knowing the rate of uptake in a tumor and clearance from the plasma and normal tissues also provides estimates of ratios between tumor and normal tissue concentrations, and these ratios are important in both imaging and therapy. These examples illustrate the utility of combining theoretical analysis also suggest ways to rationally improve uptake, and determining the limiting rates is the first step in overcoming these problems.”
Rudnick teaches on p. 155, Col. 2:
“Not strictly limited to tumor cells, target antigen is commonly expressed on normal tissue, found in circulation, and shed into the tumor interstitial space. These nontarget pools of antigens can reduce treatment effectiveness, increase systemic clearance, and increase side-effects (especially for radioimmunoconjugates) by impairing mAb specificity for the tumor.”
and on p. 158, Col. 2, last ¶ - p. 159, Col. 1:
“…antigen selection will be a critical factor for internalization and catabolism of mAbs. The relative rates of antigen recycling and dissociation are important in mAb penetration into tumors. Therefore, in applications dependent on targeting every cell of a tumor, the mAb needs to dissociate before it is internalized and degraded. In the case of ADCC, a slow internalizing antigen would be the best target. However, if one is trying to deliver a cytotoxic agent to the cytoplasm of cells in a limited region of a tumor, such as the vasculature, a mAb with slow dissociation targeting a rapidly recycling antigen would be appropriate. These are just simple examples of the interplay of affinity, avidity, and efficacy in tumor targeting.”
Huang supports and substantiates the challenges for recombinant antibodies as immunotherapeutic agents (p. 403 and 408):
“Genetic engineering has long been employed to increase the affinity of mAb to its target by altering the amino acid sequence in complementary determining region (CDR; Maynard and Georgiou 2000; Reff et al. 2002). However, high specificity must be maintained while increasing antibody affinity as it might augment cross reactivity with other nonspecific antigens, causing unwanted side effects (Hu et al. 2009). High-affinity CDR also can be suboptimal for targeting solid tumors; thus, a suitable affinity may need to be determined (Chames et al. 2009).”
“Many hurdles remain, however, due to the complexity of human immunology as demonstrated by our limited success in chronic infectious diseases and cancer. The approach to combine both active and passive immunotherapies to have synergic effects to maximize desired immune responses may lead a way for treatments of these diseases in the near future.”
Whether undue experimentation is required is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations.” Streck, Inc. v. Research & Diagnostic Systems, 665 F.3d 1269 (Fed. Cir. 2012)).
The observations set forth above and the absence of extrinsic evidence to support and further enable the scope of the method claims as broadly drawn, and the recognized unpredictability of the immunotherapeutic arts based on the record art references, support and substantiate the Examiner’s position that the ordinary artisan could not practice the full scope of the claimed method absent undue experimentation.
Therefore, due to the unpredictability of immunotherapeutics in general, and in view of the insufficient guidance and/or working examples concerning the use of the claimed monospecific and bispecific antibodies as immunotherapeutic agents, in vivo, in combination with the second agents, one skilled in the art could reasonably conclude that the broadly claimed invention was not fully supported in the specification, and thereby removing applicants from full possession of the 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.
10. Claims 20-26, 29, 34-38, 40, 42-43, 49-51, 53-56, and 58 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 20-29, 34, 36, 37, and 54-60 of copending Application No. 18/008,089 (reference application US 20230235075). The reference is not afforded safe harbor protection under 35 USC 121 because it shares no continuity nor restriction/speciation with the claims of the instant application.
Although the claims at issue are not identical, they are not patentably distinct from each other because the scope of the claims renders obvious that of the instant claims.
Ref claims
1. (Currently Amended): An anti-CD93 construct comprising an antibody moiety comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein:a) the VH comprises [[the ]]an_HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 17, [[the ]]anHC-CDR2 comprising the amino acid sequence of SEQ ID NO: 18, and [[the ]]anHC-CDR3 comprising the amino acid sequence of SEQ ID NO: 19, and the VLcomprises [[the ]]anLC-CDR1 comprising the amino acid sequence of SEQ ID NO: 20, [[the ]]anLC- CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and [[the ]]an_LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 22;b) the VH comprises [[the ]]anHC-CDR1 comprising the amino acid sequence of SEQ ID NO: 304, [[the ]]an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 305, and [[the ]]anHC-CDR3 comprising the amino acid sequence of SEQ ID NO: 19, and the VL comprises [[the ]]anLC-CDR1 comprising the amino acid sequence of SEQ ID NO: 20, [[the ]]anLC-CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and [[the ]]anLC-CDR3 comprising the amino acid sequence of SEQ ID NO: 22;c) the VH comprises [[the ]]an_HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 17, [[the ]]anHC-CDR2 comprising the amino acid sequence of SEQ ID NO: 18, and [[the ]]anHC-CDR3 comprising the amino acid sequence of SEQ ID NO: 19, and the VLcomprises
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[[the ]]anLC-CDR1 comprising the amino acid sequence of SEQ ID NO: 301, [[the ]]anLC- CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and [[the ]]an_LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 22;d) the VH comprises [[the ]]anHC-CDR1 comprising the amino acid sequence of SEQ ID NO: 304, [[the ]]an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 305, and [[the ]]anHC-CDR3 comprising the amino acid sequence of SEQ ID NO: 19, and the VL comprises [[the ]]anLC-CDR1 comprising the amino acid sequence of SEQ ID NO: 301, [[the ]]anLC-CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and [[the ]]an_LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 22;e) the VH comprises [[the ]]an_HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 17, [[the ]]an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 18, and [[the ]]anHC-CDR3 comprising the amino acid sequence of SEQ ID NO: 19, and the VLcomprises [[the ]]anLC-CDR1 comprising the amino acid sequence of SEQ ID NO: 302, [[the ]]anLC- CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and [[the ]]an_LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 22;f) the VH comprises [[the ]]an_HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 304, [[the ]]an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 305, and [[the ]]anHC-CDR3 comprising the amino acid sequence of SEQ ID NO: 19, and the VL comprises [[the ]]anLC-CDR1 comprising the amino acid sequence of SEQ ID NO: 302, [[the ]]anLC-CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and [[the ]]anLC-CDR3 comprising the amino acid sequence of SEQ ID NO: 22;g) the VH comprises [[the ]]an_HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 17, [[the ]]an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 18, and [[the ]]anHC-CDR3 comprising the amino acid sequence of SEQ ID NO: 19, and the VLcomprises
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[[the ]]anLC-CDR1 comprising the amino acid sequence of SEQ ID NO: 303, [[the ]]anLC- CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and [[the ]]an_LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 22;h) the VH comprises [[the ]]an_HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 304, [[the ]]an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 305, and [[the ]]anHC-CDR3 comprising the amino acid sequence of SEQ ID NO: 19, and the VL comprises [[the ]]anLC-CDR1 comprising the amino acid sequence of SEQ ID NO: 303, [[the ]]anLC-CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and [[the ]]anLC-CDR3 comprising the amino acid sequence of SEQ ID NO: 22;i) the VH comprises [[the ]]an_HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 17, [[the ]]an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 18, and [[the ]]anHC-CDR3 comprising the amino acid sequence of SEQ ID NO: 19, and the VLcomprises [[the ]]anLC-CDR1 comprising the amino acid sequence of SEQ ID NO: 306, [[the ]]anLC- CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and [[the ]]an_LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 22;j) the VH comprises [[the ]]an_HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 304, [[the ]]an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 305, and [[the ]]anHC-CDR3 comprising the amino acid sequence of SEQ ID NO: 19, and the VL comprises [[the ]]anLC-CDR1 comprising the amino acid sequence of SEQ ID NO: 306, [[the ]]anLC-CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and [[the ]]an_LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 22;k) the VH comprises [[the ]]an_HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 177, [[the ]]an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 178, and [[the ]]anHC-CDR3 comprising the amino acid sequence of SEQ ID NO: 179, and the VL comprises [[the ]]anLC-CDR1 comprising the amino acid sequence of SEQ ID NO: 353, [[the ]]anLC-CDR2 comprising the amino acid sequence of SEQ ID NO: 181, and [[the ]]anLC- CDR3 comprising the amino acid sequence of SEQ ID NO: 182;
1) the VH comprises [[the ]]an_HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 177, [[the ]]an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 178, and [[the ]]anHC-CDR3 comprising the amino acid sequence of SEQ ID NO: 179, and the VL comprises [[the ]]anLC-CDR1 comprising the amino acid sequence of SEQ ID NO: 353, [[the ]]anLC-CDR2 comprising the amino acid sequence of SEQ ID NO: 354, and [[the ]]anLC- CDR3 comprising the amino acid sequence of SEQ ID NO: 182; m) the VH comprises [[the ]]anHC-CDR1 comprising the amino acid sequence of SEQ ID NO: 177, [[the ]]an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 178, and [[the ]]anHC-CDR3 comprising the amino acid sequence of SEQ ID NO: 179, and the VL comprises [[the ]]anLC-CDR1 comprising the amino acid sequence of SEQ ID NO: 180, [[the ]]anLC-CDR2 comprising the amino acid sequence of SEQ ID NO: 181, and [[the ]]anLC- CDR3 comprising the amino acid sequence of SEQ ID NO: 182; or n) the VH comprises [[the ]]an_HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 177, [[the ]]an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 178, and [[the ]]anHC-CDR3 comprising the amino acid sequence of SEQ ID NO: 179, and the VL comprises [[the ]]anLC-CDR1 comprising the amino acid sequence of SEQ ID NO: 180, [[the ]]anLC-CDR2 comprising the amino acid sequence of SEQ ID NO: 354, and [[the ]]anLC- CDR3 comprising the amino acid sequence of SEQ ID NO: 182.
2-19. (Canceled).
20. (Currently Amended): The anti-CD93 construct of claim 1, wherein: a) the VH comprises an amino acid sequence of any of SEQ ID [[NO]]NOs: 29 and 307- 312, or a variant comprising an amino acid sequence having at least about 80% sequence identity; and the VL comprises an amino acid sequence of any of SEQ ID [[NO]]NOs: 30[[,]] and 313-318, or a variant comprising an amino acid sequence having at least about 80% sequence identity, or b) the VH comprises an amino acid sequence of any of SEQ ID [[NO]]NOs: 189 and 347- 349, or a variant comprising an amino acid sequence having at least about 80% sequence identity; and the VL comprises an amino acid sequence of any of SEQ ID [[NO]]NOs: 190[[,]] and 350-352, or a variant comprising an amino acid sequence having at least about 80% sequence identity.
21. (Previously Presented): The anti-CD93 construct of claim 1, wherein the antibody moiety is an antibody or antigen-binding fragment thereof selected from the group consisting of a full- length antibody, a bispecific antibody, a single-chain Fv (scFv) fragment, a Fab fragment, a Fab' fragment, a F(ab')2, an Fv fragment, a disulfide stabilized Fv fragment (dsFv), a (dsFv)2 a Fv-Fc fusion, a scFv-Fc fusion, a scFv-Fv fusion, a diabody, a tribody, and a tetrabody.
22. (Previously Presented): The anti-CD93 construct of claim 1, wherein the antibody moiety is a full-length antibody.
23. (Currently Amended): The anti-CD93 construct of claim 1, wherein the antibody moiety has an Fc fragment [[is ]]selected from the group consisting of Fc fragments form from IgG, IgA, IgD, IgE, IgM, and combinations and hybrids thereof.
24. (Original): The anti-CD93 construct of claim 23, wherein the Fc fragment is selected from the group consisting of Fc fragments from IgG1, IgG2, IgG3, IgG4, and combinations and hybrids thereof.
25. (Previously Presented): The anti-CD93 construct of claim 23, wherein the Fc fragment has a reduced effector function as compared to the corresponding wildtype Fc fragment.
26. (Previously Presented): The anti-CD93 construct of claim 23, wherein the Fc fragment has an enhanced effector function as compared to the corresponding wildtype Fc fragment.
27. (Previously Presented): The anti-CD93 construct of claim 1, wherein the antibody moiety blocks the binding of CD93 to IGFBP7.
28. (Previously Presented): The anti-CD93 construct of claim 1, wherein the antibody moiety blocks the binding of CD93 to MMRN2.
29. (Previously Presented): The anti-CD93 construct of claim 1, wherein the CD93 is a human CD93.
30. (Previously Presented): A pharmaceutical composition comprising the anti-CD93 construct of claim 1, and a pharmaceutical acceptable carrier.
31. (Currently Amended): An isolated nucleic acid encoding the anti-CD93 construct of claim 1; or a portion thereof.
32. (Original): A vector comprising the isolated nucleic acid of claim 31.
33. (Currently Amended): An isolated host cell comprising the isolated nucleic acid of claim 31; or the vector of claim 30.
34. (Previously Presented): An immunoconjugate comprising the anti-CD93 construct of claim 1, linked to a therapeutic agent or a label.
35. (Canceled).
36. (Currently Amended): A method of treating a disease or condition CD93-positive cancer in an individual, comprising administering to the individual an effective amount of the anti CD93 construct of claim 1, or the pharmaceutical composition of claim 30.
37. (Currently Amended): The method of claim 36, wherein the disease or condition CD93- positive cancer is associated with an abnormal vascular structure.
38-53. (Canceled).
54. (New): The method of claim 36, wherein the CD93-positive cancer is a solid tumor.
55. (New): The anti-CD93 construct of claim 1, wherein the VH comprises the HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 17, the HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 18, and the HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 19, and the VL comprises the LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 20, the LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and the LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 22.
56. (New): The anti-CD93 construct of claim 20, wherein the VH comprises the amino acid sequence of SEQ ID NO: 310, and the VL comprises the amino acid sequence of SEQ ID NO: 318.
57. (New): The anti-CD93 construct of claim 22, wherein the antibody moiety comprises the VH comprising the amino acid sequence of SEQ ID NO: 310, and the VL comprising the amino acid sequence of SEQ ID NO: 318, wherein the anti-CD93 construct is a full-length antibody comprising an IgG1 Fc fragment.
58. (New): The anti-CD93 construct of claim 21, wherein the antibody moiety comprises the VH comprising the amino acid sequence of SEQ ID NO: 310, and the VL comprising the amino acid sequence of SEQ ID NO: 318, wherein the anti-CD93 construct is a bispecific antibody comprising an IgG1 Fc fragment.
59. (New): The method of claim 36, wherein the antibody moiety comprises the VHcomprising the amino acid sequence of SEQ ID NO: 310, and the VL comprising the amino acid sequence of SEQ ID NO: 318.
60. (New): The method of claim 36, wherein the antibody moiety comprises the VHcomprising the amino acid sequence of SEQ ID NO: 310, and the VL comprising the amino acid sequence of SEQ ID NO: 318, wherein the anti-CD93 construct is a full-length antibody comprising an IgG1 Fc fragment.
Claims 20 (element b) -26, 29, 34-38, 40, 42-43, 49-51, 53-56, and 58
‘170 claims are overlapping for an anti-CD93 construct wherein the VH comprises an amino acid sequence of SEQ ID NOs: 29 or 307-312 and wherein the VL comprises an amino acid sequence of SEQ ID NOs: 30 or 313-318 (claims 20 (element b) and 58).
‘170 also claims different formats of the antigen binding fragment of the antibody construct (claim 21), wherein the antibody is full length (claim 22), wherein the antibody has an Fc fragment selected from IgG (claim 23), wherein the Fc fragment is selected from IgG1 (claim 24), wherein the Fc fragment has reduced effector function (claim 25) or enhanced effector function (claim 26), and wherein the CD93 is a human CD93 (claim 29).
‘170 claims a pharmaceutical composition comprising the antibody (claim 34), a nucleic acid encoding the antibody (claim 35), a vector comprising the nucleic acid (claim 36), a host cell comprising the nucleic acid (claim 37), an immunoconjugate comprising the antibody (claim 38).
‘170 claims a method of treating a disease comprising administering the antibody (claim 40), wherein the disease is cancer (claim 42), wherein the cancer is a solid tumor (claim 43), wherein the cancer is from the Markush group (claim 49), route of administration (claim 50), and administering a second therapy (claims 51, 53-56).
The VH of SEQ ID NOs: 29 and 307-312 are 100% identical in amino acid sequence identity to the VHs of instant SEQ ID NOs: 29 and 307-312, respectively; and the VL of SEQ ID NOs: 30 and 313-318 are 100% identical to the VLs of instant SEQ ID NOs: 30 and 313-318, respectively. Further, the VH of ‘170 SEQ ID NO: 29 comprises the HCDRs 1-3 of the ref SEQ ID NOs: 17-19, respectively, with 100% sequence identity. Thus, application ‘089 claims the same anti-CD93 antibody of instant claims 20 and 58.
Most notably, ‘089 and ‘170 share identical sequence listings (see the corresponding specification) but for SEQ ID NOs: 366 and 367 that are found in claim 33 of ‘170.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
12. Claims 20 (element a)-26, 29-38, 40, 42-43, 49-51, 53-56, and 58-59 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 20-38, and 54-58 of copending Application No. 18/018,568 (reference application US 20230322935). The reference is not afforded safe harbor under 35 USC 121 because it shares no continuity or a restriction/speciation with the claims of the instant application.
Ref claims
1. (Currently amended): An anti-CD93 construct comprising an antibody moiety comprising a heavy chain variable region (VH) and a light chain variable region (VL) the VH[-2]] comprises the HC-CDR1 comprising the amino acid sequence of SEQ ID NO:289, the HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 290, and the HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 291, and the VL[-2]] comprises the LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 292, the LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 293, and the LC-CDR3 comprising the amino acid sequence of SEQ ID N0:294.
20. (Currently amended): The anti-CD93 construct of claim 1[[9]], wherein, the VH comprises an amino acid sequence of any of SEQ ID NO: 287 and 319-321, or a variant comprising an amino acid sequence having at least about 80% sequence identity; and the VLcomprises an amino acid sequence of any of SEQ ID NO: 288, and 322-324, or a variant comprising an amino acid sequence having at least about 80% sequence identity.
21. (Currently amended): The anti-CD93 construct of any one of claim[[s]] 1[[-20]], wherein the antibody moiety is an antibody or antigen-binding fragment thereof selected from the group consisting of a full-length antibody, a bispecific antibody, a single-chain Fv (scFv) fragment, a Fab fragment, a Fab' fragment, a F(ab')2, an Fv fragment, a disulfide stabilized Fv fragment (dsFv), a (dsFv)2 a Fv-Fc fusion, a scFv-Fc fusion, a scFv-Fv fusion, a diabody, a tribody, and a tetrabody.
22. (Currently amended): The anti-CD93 construct of claim [[2]]1, wherein the antibody moiety is a full-length antibody.
23. (Currently amended): The anti-CD93 construct of any one of claim[[s]] 1[[-22]], wherein the antibody moiety has an Fc fragment is selected from the group consisting of Fc fragments form IgG, IgA, IgD, IgE,IgM, and combinations and hybrids thereof.
24. (Original): The anti-CD93 construct of claim 23, wherein the Fc fragment is selected from the group consisting of Fc fragments from IgG1,IgG2, IgG3, IgG4, and combinations and hybrids thereof.
25. (Currently amended): The anti-CD93 construct of claim 23 or claim 24, wherein the Fc fragment has a reduced effector function as compared to the corresponding wildtype Fc fragment.
26. (Currently amended): The anti-CD93 construct of claim 23 or claim 24, wherein the Fc fragment has an enhanced effector function as compared to the corresponding wildtype Fc fragment.
27. (Currently amended): The anti-CD93 construct of any one of claim[[s]] 1[[-26]], wherein the antibody moiety blocks the binding of CD93 to IGFBP7.
28. (Currently amended): The anti-CD93 construct of any one of claim[[s]] 1[[-27]], wherein the antibody moiety blocks the binding of CD93 to MMRN2.
29. (Currently amended): The anti-CD93 construct of any one of claim[[s]] 1[[-22]], wherein the CD93 is a human CD93.
30. (Currently amended): A pharmaceutical composition comprising the anti-CD93 construct of any one of claim[[s]] 1 [[-29]], and a pharmaceutical acceptable carrier.
31. (Currently amended): An isolated nucleic acid encoding the anti-CD93 construct of any oneof claim[[s]] 1 [[-29]] or a portion thereof.
32. (Original): A vector comprising the isolated nucleic acid of claim 31.
33. (Currently amended): An isolated host cell comprising the isolated nucleic acid of claim 31;or the vector of claim 30.
34. (Currently amended): An immunoconjugate comprising the anti-CD93 construct of any one of claim[[s]] 1[[-29]], linked to a therapeutic agent or a label.
35. (Original): A method of producing an anti-CD93 construct comprising: a) culturing the isolated host cell of claim 33 under conditions effective to express the anti-CD93 construct; and b) obtaining the expressed anti-CD93 construct from the host cell.
36. (Currently amended): A method of treating a disease or condition in an individual, comprising administering to the individual an effective mount of the anti-CD93 construct of any one of claim[[s]] 1[[-29]], or the pharmaceutical composition of claim 30.
37. (Original): The method of claim 36, wherein the disease or condition is associated with an abnormal vascular structure.
38. (Currently amended): The method of claim 36 or claim 37, wherein the disease or condition is a cancer.
39-53. (Cancelled)
54. (New) The anti-CD93 construct of claim 1, wherein:(a) the VHcomprises an amino acid sequence of SEQ ID NO: 287, and wherein the VLcomprises an amino acid sequence of SEQ ID NO: 288; (b) the VHcomprises an amino acid sequence of SEQ ID NO: 287, and wherein the VLcomprises an amino acid sequence of SEQ ID NO: 322; (c) the VHcomprises an amino acid sequence of SEQ ID NO: 287, and wherein the VLcomprises an amino acid sequence of SEQ ID NO: 323; (d) the VHcomprises an amino acid sequence of SEQ ID NO: 287, and wherein the VLcomprises an amino acid sequence of SEQ ID NO: 324; (e) the VHcomprises an amino acid sequence of SEQ ID NO: 319, and wherein the VLcomprises an amino acid sequence of SEQ ID NO: 288; (f) the VHcomprises an amino acid sequence of SEQ ID NO: 319, and wherein the VLcomprises an amino acid sequence of SEQ ID NO: 322; (g) the VHcomprises an amino acid sequence of SEQ ID NO: 319, and wherein the VLcomprises an amino acid sequence of SEQ ID NO: 323; (h) the VHcomprises an amino acid sequence of SEQ ID NO: 319, and wherein the VLcomprises an amino acid sequence of SEQ ID NO: 324; (i) the VHcomprises an amino acid sequence of SEQ ID NO: 320, and wherein the VLcomprises an amino acid sequence of SEQ ID NO: 288; (j) the VHcomprises an amino acid sequence of SEQ ID NO: 320, and wherein the VLcomprises an amino acid sequence of SEQ ID NO: 322; (k) the VHcomprises an amino acid sequence of SEQ ID NO: 320, and wherein the VLcomprises an amino acid sequence of SEQ ID NO: 323;(1) the VHcomprises an amino acid sequence of SEQ ID NO: 320, and wherein the VLcomprises an amino acid sequence of SEQ ID NO: 324; (m) the VHcomprises an amino acid sequence of SEQ ID NO: 3217 and wherein the VLcomprises an amino acid sequence of SEQ ID NO: 288; (n) the VHcomprises an amino acid sequence of SEQ ID NO: 321, and wherein the VLcomprises an amino acid sequence of SEQ ID NO: 322; (o) the VHcomprises an amino acid sequence of SEQ ID NO: 321, and wherein the VLcomprises an amino acid sequence of SEQ ID NO: 323; (p) the VHcomprises an amino acid sequence of SEQ ID NO: 321, and wherein the VLcomprises an amino acid sequence of SEQ ID NO: 324.
55. (New) The anti-CD93 construct of claim 1, wherein the VHcomprises an aminoacid sequence of SEQ ID NO: 321, and wherein the VLcomprises an amino acid sequence of SEQ ID NO: 324.
56. (New) An anti-CD93 construct, wherein the construct comprises a first moiety that binds to CD93 and a second moiety that binds to VEGF, wherein the first moiety comprises the anti- CD93 antibody moiety of claim 1.
57. (New) The anti-CD93 construct of claim 56, wherein the anti-CD93 antibody moiety is an anti-CD93 full-length antibody comprising two heavy chains and two light chains, and wherein the second moiety is fused to C-terminus of both of the heavy chains of the anti-CD93 full-length antibody.
58. (New) The anti-CD93 construct of claim 56, wherein the two heavy chains fused with the second moiety each comprises the amino acid sequence set forth in SEQ ID NO: 342 or 366, or a variant comprising an amino acid sequence having at least about 80% sequence identity, and wherein the two light chains each comprise the amino acid sequences set forth in SEQ ID NO: 343 or 367, or a variant comprising an amino acid sequence having at least about 80% sequence 12identity.
Claims 20 (element a) - 26, 29-38, 40, 42-43, 49-51, 53-56, and 58-59
‘170 claims are overlapping for an anti-CD93 construct wherein the VH comprises an amino acid sequence of SEQ ID NOs: 287 or 319-321 and wherein the VL comprises an amino acid sequence of SEQ ID NOs: 288 or 322-324 (claims 20 (element a), 30 and 58).
‘170 also claims different formats of the antigen binding fragment of the antibody construct (claim 21), wherein the antibody is full length (claim 22), wherein the antibody has an Fc fragment selected from IgG (claim 23), wherein the Fc fragment is selected from IgG1 (claim 24), wherein the Fc fragment has reduced effector function (claim 25) or enhanced effector function (claim 26), and wherein the CD93 is a human CD93 (claim 29).
‘170 claims a bispecific antibody anti-CD93 x anti-VEGF, where the anti-CD93 VH/VL CDR1-3 are 289-290-291 and 292-293-294, respectively (claim 30), the VH comprise SEQ ID NOs: 287 or 319-321 and wherein the VL comprises an amino acid sequence of SEQ ID NOs: 288 or 322-324 (claim 31), the format of the bispecific antibody (claim 32) and the heavy chains (SEQ ID NO: 342 or 366) and light chains (SEQ ID NO: 343 or 367).
‘170 claims a pharmaceutical composition comprising the antibody (claim 34), a nucleic acid encoding the antibody (claim 35), a vector comprising the nucleic acid (claim 36), a host cell comprising the nucleic acid (claim 37), an immunoconjugate comprising the antibody (claim 38).
‘170 claims a method of treating a disease comprising administering the antibody of claim 20 (claim 40), wherein the disease is cancer (claim 42), wherein the cancer is a solid tumor (claim 43), wherein the cancer is from the Markush group (claim 49), route of administration (claim 50), and administering a second therapy (claims 51, 53-56).
‘170 claims a method of treating a disease comprising administering the bispecific antibody of claim 30 (claim 59).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
13. No claims are allowed.
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN A. BRISTOL whose telephone number is (571)272-6883. The examiner can normally be reached Mon-Fri 9 AM-5 PM.
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LYNN ANNE BRISTOL
Primary Examiner
Art Unit 1643
/LYNN A BRISTOL/Primary Examiner, Art Unit 1643