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 1-103 are the original claims filed 8/26/2022. In the Preliminary Amendment of 8/26/2022, Claims 1, 18, 21, 24, 27, 30, 47, 50, 52, 54, 57, 60, 64-66, 68, 69, 84, 86-87, 89-91, and 102 are amended and Claims 2-17, 19-20, 22-23, 25-26, 28-29, 31-46, 48-49, 55-56, 58-59, 61-63, 67, 70-83, 85, 92-101, and 103 are canceled. In the Response of 11/24/2025, Claims 1, 18, 21, 24, 27, 30, 65, 66, 68, 69, 90, and 91 are amended, and claim 57 is canceled.
Claims 1, 18, 21, 24, 27, 30, 47, 50-54, 60, 64-66, 68- 69, 84, 86-91, and 102 are all the claims.
The Office Action is final.
Priority
2. USAN 17/822,737 filed 08/26/2022, is a Continuation of PCT/CN2021/078051, filed 02/26/2021, claims foreign priority to PCT/CN2020/077148, filed 02/28/2020.
Information Disclosure Statement
3. As of 1/15/2026, a total of three (3) IDS are filed: 8/26/2022; 7/30/2024; and 2/4/2025. The corresponding initialed and dated 1449 form is considered and of record.
Withdrawal of Objections
Drawings
4. The objection to the drawing sheets for Figures 1 and 8 because they include the term “Octet”, which is a trade name or a mark used in commerce, is withdrawn. The drawings were received on 11/24/2025. These drawings are acceptable.
Specification
5. The objection to the disclosure because of informalities is withdrawn. Both clean and marked-up copies of the specification are included in the response.
a) The replacement specification rectifies the improper use of the term Octet, ForteBio, ATCC, BiaCORE, Sepharose, Tween, Tris, nanobody, BiTE, DuoBody, Alexa Fluor, AffiniPure, CytExpert, Graphpad, Capto, Avant, ExpiCHO, Gibco, KINEXA, DNASTAR, MUSCLE, Megalign, which is a trade name or a mark used in commerce.
b) The replacement specification rectifies the misspelling for “fortebio.”
c) The replacement specification rectifies the improper citation of amino acid sequences > 4 amino acids in length that pursuant to 37 CDR 1.821-1.825 are required to be identified by sequence identifier.
Claim Objections
6. The objection to Claims 1, 18, 21, 24, 27, 30, 47, 50-54, 57, 60, 64-66, 68- 69, 84, 86-91, and 102 because of informalities is moot for the canceled claim and withdrawn for the pending claims.
a) Claims 1, 18, 21, 24, 27, 30, 47, 50-54, 57, 60, 64-66, 68- 69, 84, 86-91, and 102 are amended to recite “human CD137” and “human EGFR”.
b) Claims 1, 18, 21, 24, 27, 30, 47, 50-54, 57, 60, 64-66, 68- 69, 84, 86-91, and 102 are amended to correct improper punctuation
c) Claims 57 is canceled and claims 65 and 66 are amended to recite “(VL-2).”
d) Claim 90 is amended to recite “…under conditions
Withdrawal of Rejections
Claim Rejections - 35 USC § 112(b)
7. The rejection of Claims 27 and 64 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn.
a) Claim 27 is amended to delete the limitation “(e.g., a bispecific antibody)”.
b) Claim 27 is amended to delete the recitation “multispecific antibody”, “(e.g., a bispecific antibody), a scFv-Fv fusion, a diabody, a tribody, and a tetrabody”.
c) Claim 1, and from which claim 64 depends, is amended to recite a VH-2 and VL-2 to render proper the antecedent basis for claim 64.
Claim Rejections - 35 USC § 112(d)
8. The rejection of Claim 27 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form is withdrawn.
Claim 27 is amended to delete the species “a multispecific antibody.”
Claim Rejections - 35 USC § 112(a)
Enablement
9. The rejection of Claim 91 (prevention (non-elected)) under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement is withdrawn. Claim 91 is amended to delete “preventing a disease”.
Rejections Maintained
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.
Scope of Enablement
10. The rejection of Claim 91 (treatment) under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is maintained.
a) Applicants allege amending claim 91 to recite a method of treating a cancer or tumor in a subject overcomes the rejection.
Response to Arguments
The specification, while being enabling for, in vivo, anti-tumor effect using the 2-9-1 IG1 SELF and 2-9-1 IgG2 SELF cones, does not reasonably provide enablement for treating just any cancer or tumor with any one or more of the bispecific antibodies (anti-CD137 x anti-EGFR) of claim 1.
b) Applicants allege it is disclosed in the specification that a multispecific anti- CD137/EGFR antibody comprising an exemplary anti-CD137 binding moiety and an exemplary anti-EGFR binding moiety is effective in treating multiple types of tumors in vivo. For example, the in vivo efficacy evaluation for Example 4 demonstrates that the exemplary anti-CD137/EGFR antibody is effective in treating tumors in both a human colon cancer animal model and a human epidermoid cancer animal model. See As- Filed Specification at 145-147.
Response to Arguments
Applicants rely on Attorney arguments that are not substantiated by intrinsic or extrinsic evidence showing that in vivo use of just any one of the anti-hCD137 (a)-(p) clones paired with just any one anti-hEGFR (a)-(e) clones of claim 1, are effective in treating just any cancer or tumor. The relationship of the cancer/tumor expressing any marker related or unrelated to one or both the markers, CD137 and/or EGFR, and being treatment responsive to the alleged bispecific antibody has not been demonstrated by Applicants. MPEP 716.01 and 2145 (The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997))
c) Applicants allege the alternative anti-CD137 binding moieties and the alternative anti-EGFR binding moieties recited in claim 1 can similarly bind to CD137 and EGFR, respectively, compared to those comprised in the exemplary anti- CD137/EGFR antibody, a person of skill in the art would reasonably extrapolate the antitumor function of the exemplary anti-CD137/EGFR antibody to an anti-CD137/EGFR antibody that comprises an alternative anti-CD137 binding moiety and an alternative anti-EGFR binding moiety recited in claim 1.
Response to Arguments
Applicants rely on Attorney arguments that are not substantiated by intrinsic or extrinsic evidence showing the POSA can reasonably extrapolate that “an anti-CD137/EGFR antibody that comprises an alternative anti-CD137 binding moiety and an alternative anti-EGFR binding moiety recited in claim 1” would function as a therapeutic antibody in vivo. MPEP 716.01 and 2145 (The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997))
The cited reference art from the Office Action of 8/22/2026 is dispositive to the summarization of Applicants comments. The reference art teaches that antibody development and testing is not only unpredictable but burdensome.
The response is incomplete.
Disclosure in the Specification
To find support and enablement in the specification for the claimed invention, the POSA must extrapolate from the limited actual data in a field that is generally unpredictable for therapeutic antibodies.
Example 2 characterizes the anti-CD137 antibodies generated from mouse hybridomas of Example 1. For, in vivo, efficacy of monospecific anti-CD137 antibodies see Example 2.E. and Table 8. The two candidates profiled are: 2-9-1 IgG1 SELF (dosed at 0.3, 1 or 10 mg/kg); and 2-9-1 IgG2 SELF (dosed at 1 mg/kg), and shown to be therapeutically effective in reducing tumor growth in mice bearing the MC38 murine colon cancer at 24 days post administration.
For, in vivo, efficacy of a bispecific anti-CD137 x anti-EGFR antibody see Example 4.D. and Table 10. The candidate profiled is 2-9 clone fused to the EGFR full length antibody of WO2015184403 (anti-CD137 x anti-EGFR IgG1 Fc LALA; IDS 8/26/20220). The anti-CD137 x anti-EGFR IgG1 Fc LALA clone exhibited dose dependent inhibition of tumor growth suppression of the LoVo tumor, in vivo. In Table 11, the anti-CD137 x anti-EGFR IgG1 Fc LALA clone exhibited inhibition of tumor growth suppression of the LoVo human colon cancer tumor cell line, in vivo, that was more than that for the combination of the separate antibodies administered together. In Table 12, the anti-CD137 x anti-EGFR IgG1 Fc LALA clone exhibited inhibition of tumor growth suppression of the A431 human epidermoid cancer tumor cell line, in vivo, that was more than that for the combination of the separate antibodies administered together.
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).
Prior Art Status: Translation of Therapeutics from In vitro to In vivo is Unpredictable
A tumor is a 3-dimensional complex consisting of interacting malignant and non-malignant cells. Vascularisation, perfusion and drug access to the tumor cells are not evenly distributed and this is an important source of heterogeneity in tumor response to drugs. Therefore, prediction of drug effects in an animal subject based solely on in vitro cell based assays or limited in vivo assays is not reliable and further evaluation in animal tumor systems is essential.
Further, inasmuch as in vivo animal drug testing may be a platform technology in a determination of enablement, the complexity and difficulty of drug delivery for cancer treatment is underscored by Voskoglou-Nomikos (Clin. Can. Res. 9:4227-4239 (2003)). Voskoglou-Nomikos conducted a study using the Medline and Cancerlit databases as source material in comparing the clinical predictive value of three pre-clinical laboratory cancer models: the in vitro human cell line (Figure 1); the mouse allograft model; and the human xenograft model (Figures 2 and 3). Significantly when each of the cancer models was analyzed against Phase II activity, there was a negative correlation for the in vitro human cell line models being predictive of good clinical value. No significant correlations between preclinical and clinical activity were observed for any of the relationships examined for the murine allograft model. And the human xenograft model showed good tumor-specific predictive value for NSCLC and ovarian cancers when panels of xenografts were used, but failed to predict clinical performance for breast and colon cancers. Voskoglou-Nomikos suggests that “the existing cancer models and parameters of activity in both the preclinical and clinical settings may have to be redesigned to fit the mode of action of novel cytostatic, antimetastatic, antiangiogenisis or immune-response modulating agents” and “New endpoints of preclinical activity are contemplated such as the demonstration that a new molecule truly hits the intended molecular target” (p.4237, Col. 1, ¶6).
Dennis (Nature 442:739-741 (2006)) also recognizes that human cancer xenograft mouse models for testing new drugs has been and will remain the industry standard or model of choice, but it is not without problems because “many more [drugs] that show positive results in mice have little or no effect in humans” (p. 740, Col. 1, ¶3). Dennis describes transgenic animal mouse models as an alternative to xenograft modeling and the general differences between mice and humans when it comes to tumor modeling: 1) cancers tend to form in different types of tissue, 2) tumors have fewer chromosomal abnormalities, 3) ends of chromosomes (telomeres) are longer, 4) telomere repairing enzyme active in cells, 5) short lifespan, 6) fewer cell divisions (1011) during life than humans (1016), 7) metabolic rate seven time higher than humans, and 8) lab mice are highly inbred and genetically similar.
Cespdes et al. (Clin. Transl. Oncol. 8(5):318-329 (2006)) review the some of the examples of art-recognized animal disease model correlates for the corresponding human disease in Tables 1-3. Cespedes emphasizes the challenges in using animal models as predictive correlates for human responsiveness to therapeutics and sets forth on pp. 318-319 a list of criteria that would represent the ideal in vivo model for studying cancer therapeutics. As regards the use of xenograft modeling, Cespedes teaches:
"One limitation of the xenograft models is precisely their use of an immunocompromised host, which eliminates the possibility of studying the role of the immune system in tumor progression. Some authors also think that cancer and host cells being from different species may limit the occurrence of critical tumor-stroma interactions, leading to an inefficient signaling. The organ of implantation could also become a limitation to the system. Thus, as it has already been described, subcutaneous xenografts infrequently metastasize and are unable to predict response to drugs” (p. 325, Col. 1, ¶2).
In another thorough and detailed review of animal model testing from 2007, Talmadge et al. (Am. J. Pathol 170(3):793-804 (2007)) teach “Indeed primary human tumor xenografts can be predictive of clinical cytotoxic therapy for a given tumor histiotype provided that clinically relevant pharmacological dosing parameters are used. It is noted that human tumor cell lines in contrast to human primary tumor cells have generally been cultured for years losing much of their heterogeneity. This has resulted in undifferentiated tumors lacking the histology and cellular architecture characteristic of the modeled human tumor” (p. 795, Col. 2, ¶2)...and “xenograft tumor models can effectively predict responsive tumor histiotypes; however these models need to incorporate a pharmacological and toxicological foundation to be successful. In addition, animal models can be used to resolve a specific experimental question that can be appropriately translated into clinical trials" (p. 800, Col. 1, ¶2). “In addition to a quantitative determination of anti-tumor activity, responsive preclinical tumor models cane also be used to assess preliminary ADME (adsorption, distribution, metabolism and excretion) information and toxicity" (p. 800, Col, 2, ¶1). Talmadge states that “Before clinical testing, a new drug or drug formulation should demonstrate safety and/or efficacy profile compared with current therapeutics in animal models. The comparison should incorporate rigorous animal models and not be based on highly responsive models, such as ones with rapid outcome that are convenient or with which the investigator is familiar. Furthermore, tumor and animal models should meet specific biological criteria including heterogeneity, appropriate histology, metastatic propensity, and appropriate genetic criteria depending on the targeted drug metabolism, limited immunogenicity, and potential etiology. Last, the model should have the potential to provide a correlation between therapeutic model outcome and clinical activity, optimally with previous documentation of relevance between mice and humans” (p. 800, Col. 2, ¶3).
One skilled in the art would reasonably conclude that evidence obtained in any in vitro assay would not even necessarily correlate with results expected in any animal model. Thus, and to the extent the claim encompasses an intended in vivo treatment on any disease of any subject, and the specification does not provide sufficient guidance using the bispecific anti-CD137 x anti-EGFR antibodies in any method, in vivo, to treat any disease, Applicants are not in possession of the full scope of the invention at the time of filing.
Prior Art Status: Immunotherapeutics especially cancer therapy is unpredictable
The use of antibody immunotherapy for the treatment of tumors has been shown to have limitations. Five (5) art references in the field of immune-therapeutics 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.”
Therefore, due to the unpredictability of immune-therapeutics in general, and in view of the insufficient guidance and/or working examples concerning the use of the claimed bispecific anti-CD137 x anti-EGFR antibodies as immunotherapeutic agents, in vivo, for treating just any disease, one skilled in the art would reasonably conclude that the broadly claimed invention was not fully supported in the specification, and thereby removing applicants from full possession and enablement of the invention.
The response is incomplete and the rejection is maintained.
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.
11. The provisional rejection of Claims 1, 18, 21, 24, 27, 30, 47, 50-54, 60, 64-66, 68- 69, 84, 86-91, and 102 on the ground of nonstatutory double patenting as being unpatentable over claims 4, 18, 21, 24, 27, 30, 49-54, 57, 59-61, 63-64, 76-82, and 94 of copending Application No. 17/822,750 (reference application US 20220403040) is moot for the canceled claims and maintained for the pending claims.
Applicants allege the claims of co-pending U.S. Application No. 17/822,750 do not teach or suggest all limitations of amended claim 1. For example, the claims of the reference applications do not teach or suggest, at least, a multispecific antibody "comprising a first antibody moiety that binds to human CD137 and a second antibody moiety that binds to human EGFR," wherein "the first antibody moiety comprises a heavy chain variable region (VH) ...and a light chain variable region (VL)" and wherein "the second antibody moiety comprises ... a second heavy chain variable region (VH-2) and a second light chain variable region (VL-2)" with sequences as recited in amended claim 1.
Response to Arguments
Reference claim 4 is drawn to a multispecific antibody comprising an anti-CD137 moiety x an anti-HER2 moiety that does not recite the CDR1-3 for the anti-HER2 moiety.
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Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the reference application comprise identical anti-CD137 VHCDR1-3/ VLCDR1-3 pair in elements (a)-(n):
(a)
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The claim sets are not from a restricted parent application, share no continuity, and share no speciation for a second antigen (e.g., EGFR or HER2). The core invention for both claim sets are the anti-CD 137 constructs that bind to CD 137, including multispecific anti- CD137 antibodies with binding specificity for CD 137 and one or more additional antigens, and methods of using the same. See the abstract from ‘750.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
12. The provisional rejection of Claims 1, 18, 21, 24, 27, 30, 47, 50-54, 60, 64-66, 68- 69, 84, 86-91, and 102 on the ground of nonstatutory double patenting as being unpatentable over claims 4, 17, 20, 23, 26-30, 33, 35, 36, 38, 45, 47-52, and 61 of copending Application No. 17/822,710 (reference application US 20240076395) is moot for the canceled claims and maintained for the pending claims.
The reference application is not afforded safe harbor under 35 USC 121 because it does not share continuity nor a restriction/speciation with the claims of the instant application.
Applicants allege the claims of co-pending U.S. Application No. 17/822,710 do not teach or suggest all limitations of amended claim 1. For example, the claims of the reference applications do not teach or suggest, at least, a multispecific antibody "comprising a first antibody moiety that binds to human CD137 and a second antibody moiety that binds to human EGFR," wherein "the first antibody moiety comprises a heavy chain variable region (VH) ...and a light chain variable region (VL)" and wherein "the second antibody moiety comprises ... a second heavy chain variable region (VH-2) and a second light chain variable region (VL-2)" with sequences as recited in amended claim 1.
Reference claim 4 is drawn to an anti-CD137 antibody that shares 100% identity to the VH/VL CDR1-3 of the instant claim set.
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282
1062
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Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the reference application comprise identical anti-CD137 VHCDR1-3/ VLCDR1-3 pair in elements (a)-(n):
(a)
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382
1030
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376
1004
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(b)
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376
982
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382
962
media_image5.png
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(c)
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374
988
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380
996
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(d)
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390
980
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380
982
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(e)
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380
966
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390
1008
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(f)
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384
964
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380
994
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(g)
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388
964
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media_image15.png
378
980
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(h)
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440
968
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378
978
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(i)
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412
1000
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390
954
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(j)
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388
980
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382
974
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(k)
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392
1024
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382
962
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(l)
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374
978
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374
974
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(m)
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370
982
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382
968
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(n)
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382
1020
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386
1010
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(o)
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384
1028
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380
1006
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(p)
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378
1016
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382
966
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The claim sets are not from a restricted parent application, share no continuity, and share no speciation for a second antigen (e.g., EGFR or HER2). The core invention for both claim sets are the anti-CD137 constructs that bind to CD137 (e.g., anti-CD137 monoclonal antibodies and multispecific antibodies. See the abstract from ‘710.
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. THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
15. 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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu Julie can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
LYNN ANNE BRISTOL
Primary Examiner
Art Unit 1643
/LYNN A BRISTOL/Primary Examiner, Art Unit 1643