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. Claim 1 is the original claim filed on 3/20/2023. Claim 1 is the pending claim.
Priority
2. USAN 18/186,783, filed 03/20/2023, is a Continuation of 17/817,133, filed 08/03/2022, now abandoned, 17/817,133 is a Continuation of 17/645,272, filed 12/20/2021, now abandoned, 17/645,272 is a Continuation of 16/269,413, filed 02/06/2019, now abandoned, 16/269,413 is a Continuation of 15/493,559, filed 04/21/2017, now abandoned, 15/493,559 is a Continuation of 14/935,309, filed 11/06/2015, now abandoned, claims foreign priority to EP 14192175.9, filed 11/06/2014, claims foreign priority to EP 15188056.4, filed 10/02/2015.
Information Disclosure Statement
3. As of 10/29/2025, a total of one (1) IDS is filed: 3/20/2023. The corresponding initialed and dated 1449 form is considered and of record.
Objections
Drawings
4. The drawing sheets for Figures 2A-2B are objected to because the y-axis label is overlapping the y-coordinates. 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 disclosure is objected to because of the following informalities:
a) The use of the term, Alexa, LSRFortessa, CellTiter-Glo, FACSCanto, Ficoll-Paque, OptEIA, FACSCalibur, BiaCore, DNASTAR, UNIX, megalign, 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) Amend the specification to replace “4oC” with “4ºC.”
c) The specification contains peptide sequences > 4 amino acids in length that pursuant to 37 CFCR 1.1821-1.825 are required to be identified by SEQ ID NO. See pp 68-73 in the original filed specification.
Appropriate correction is required.
Claim Objections
6. Claim 1 is objected to because of the following informalities:
a) Amend claim 1 to distinguish the conditions under which cellular internalization occur(s) from the FACS analysis of the cells.
For example, an isolated antibody that binds to TIM3, wherein the antibody [: ·] induces internalization of TIM3 -expressing RPMI_8226 cells by at least 45% after 120 minutes at 37° C, wherein the internalization is measured by FACS.
b) Amend claim 1 to replace “Minute” with “minute.”
c) Amend claim 1 to delete “[: ·].”
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.
7. Claim 1 is 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) Claim 1 contains the trademark/trade names “ATCC®” and CCL-155™. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe the American Type Culture Collection and the RPMI8226 cell line (human plasmacytoma), respectively, accordingly, the identification/description is indefinite.
b) Claim 1 is indefinite for reciting parenthetical text where it is indiscernible if the text is exemplary or intended descriptive subject matter. See MPEP § 2173.05(d).
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.
Written Description
8. Claim 1 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim interpretation
Claim 1 is are directed to an isolated antibody that binds to TIM3, wherein the antibody induces internalization of TIM3 in a FACS assay on TIM3 expressing RPMI8226 cells (ATCC ® CCL-155TM)) of at least 45% after 120 Minutes at 37ºC”.
“Antibody”: the specification teaches inclusion of fragments comprising less than a parental VH/VL domain pairing
[0294] Single-domain antibodies are antibody fragments comprising all or a portion of the heavy chain variable domain or all or a portion of the light chain variable domain of an antibody. In certain embodiments, a single-domain antibody is a human single-domain antibody (Domantis, Inc., Waltham, MA; see, e.g., U.S. Pat. No. 6,248,516 B1).
The claim does not distinguish the anti-TIM3 antibody being polyclonal, monoclonal or chimeric:
[0090] The term “monoclonal antibody” as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical and/or bind the same epitope, except for possible variant antibodies, e.g., containing naturally occurring mutations or arising during production of a monoclonal antibody preparation, such variants generally being present in minor amounts. In contrast to polyclonal antibody preparations, which typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody of a monoclonal antibody preparation is directed against a single determinant on an antigen. Thus, the modifier “monoclonal” indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies, and is not to be construed as requiring production of the antibody by any particular method. For example, the monoclonal antibodies to be used in accordance with the present invention may be made by a variety of techniques, including but not limited to the hybridoma method, recombinant DNA methods, phage-display methods, and methods utilizing transgenic animals containing all or part of the human immunoglobulin loci, such methods and other exemplary methods for making monoclonal antibodies being described herein.
The claim does not distinguish the anti-TIM3 antibody from a parental antibody much less a variant thereof.
The interpretation encompasses a genus of anti-TIM3 antibodies beyond those taught in the specification. Because applicant seeks patent protection for all such functionalized anti-TIM3 antibodies, this genus must be adequately described.
A description adequate to satisfy 35 U.S.C. § 112(a) must clearly allow persons of ordinary skill in the art to recognize that the inventor invented what is claimed (Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc) (citation omitted, alteration in original). The purpose of the written description requirement is to “ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent’s specification” (In re Katz Interactive Call Processing Patent Litig. 639 F.3d 1303, 1319 (Fed. Cir 2011).
Scope of the claimed genus
The anti-TIM3 antibody is described solely in terms of function, i.e. binding TIM3 and inducing internalization. This does not provide a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials. The TIM3 antigen (e.g., human, rat, mouse, rabbit) is not even described by a structure relevant to the genus of anti-TIM3 antibodies that binds the structure.
Here, all of the claims encompass anti-TIM3 antibodies, and variations to the VH and VL domains, in which the variable domains, including the complementarity determining regions (CDRs) could vary relative to the VLC and VHC and CDRs found in the parental antibody in addition to the VL frameworks and VH frameworks. The encompassed antibodies are allowed to comprise single variable domains of either a VH or VL. The genus encompassed by the claim is therefore very large and there is substantial variation within the genus.
State of the Relevant Art
By the time the invention was made, it was well-established in the art that the formation of an intact antigen-binding surface on an antibody required the association of the complete heavy and light chain variable regions, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope (Almagro & Franssen, Frontiers in Bioscience, 13:1619-33 (2008) (PTO-892) (see Section 3 “Antibody Structure and the Antigen Binding Site” and Figure 1). While this overall architecture is shared among antibodies from a wide variety of sources (human, rat, mouse, rabbit), the structure each antibody uses to bind its particular epitope on an antigen is structurally distinct and is formed by a recombination event that results in high variability at the amino acid sequence level, even when the same antigen is bound (Edwards et al., J Mol Biol 334:103-118 (2003) (PTO-892); see also Marchalonis et al., Dev & Comp Immunol. 30:223-247 (2006) (PTO-892), summarized in Abstract and Conclusion.
Methods of preparing antibodies from a variety of species to a protein or peptide of interest were well-established in the art at the time the invention was made. But application of those methods to any given antibody was still a matter of trial-and-error testing, and the skilled person could not automatically predict which residues in the CDRs would be tolerant of mutations, or which amino acid substitutions would maintain antigen binding. Overall, at the time the invention was made, the level of skill for preparing antibodies and then selecting those antibodies with desired functional properties was high. For example, it is generally the case that absent the fundamental structure provided for by all six CDRs of a parental antibody in the context of appropriate VH and VL framework sequences, a person of ordinary skill cannot visualize or otherwise predict, what an antibody with a particular set of functional properties would look like structurally.
Moreover, persons of ordinary skill in the art have long since acknowledged that even minor changes in the amino acid sequences of the VH and VL, particularly in the CDRs, may dramatically affect antigen-binding function. Lippow, for example, teaches that a single point mutation in the CDR of a parent antibody led to as much as an eightfold improvement in binding affinity in the resulting mutant (p. 1172, left col., lines 7-8 from end of first full paragraph and Table 1a) (Lippow et al., “Computational design of antibody-affinity improvement beyond in vivo maturation,” Nature Biotechnology, 25(10):1171-1176 (2007) (PTO-892).
Sulea teaches that individual point mutations gave an improvement of one order of magnitude in binding affinity, which in turn, generated a 6-fold enhancement of efficacy at the cellular level (Abstract) (Sulea et al., “Application of Assisted Design of Antibody and Protein Therapeutics (ADAPT) improves efficacy of a Clostridium difficile toxin A single-domain antibody," Scientific Reports, 8(260):1-11 (2018) (PTO-892). Hasegawa et al. reports that a single amino acid substitution in the variable region was sufficient to alter the efficiency of biosynthesis and the variant antibody acquired stronger binding affinity to its antigen than the parent (Hasegawa et al., “Single amino acid substitution in LC-CDR1 induces Russell body phenotype that attenuates cellular protein synthesis through elF2a phosphorylation and thereby downregulates IgG secretion despite operational secretory pathway traffic,” MABS, VOL. 9, NO. 5, pp. 854-873 (2017) (PTO-892)). Altshuler teaches that generally, “CDR mutations should not involve residues that can play structural functions (form parts of the domain ‘internal core’, internal salt bridges, hydrogen bonds, etc.).” “Usually these are conservative residues, and any substitution of these residues causes decrease[s] in affinity” (Altshuler et al., “Generation of Recombinant Antibodies and Means for Increasing Their Affinity,” Biochemistry (Moscow), 75(13):1584-1605 (2010) at p. 1600, col. 1, para. 2, lines 1-5 (PTO-892). Accordingly, a person of ordinary skill in the art would have recognized that it was highly unpredictable that any of the CDRs or FRs could be modified to create an unlimited change in amino acids for both the CDRs and FRs of the claimed antibodies, without increasing, eliminating, or in some way altering antigen binding.
Summary of species disclosed in the specification
The specification fully discloses 10 monoclonal anti-TIM3 antibody clones and none of which are instant claimed by the corresponding VHCDR1-3, VLCDR1-3 or VH/VL domains:
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Of six clones tested in an internalization assay, all six achieve at least 45% internalization by the 120-minute mark:
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The POSA could reasonably conclude that the 10 clones are not representative of multitude of the functionalized anti-TIM3 antibodies encompassed by claim 1. Applicants have not shown they are in possession of the full breadth and scope of all possible anti-TIM3 antibodies taught in the specification.
Are the disclosed species representative of the claimed genus?
It is asserted that the disclosed species taught in the specification are not representative of the claimed genus because the claims encompass polyclonal, monoclonal and chimeric anti-TIM3 antibodies including but not limited to fragments such as single VH and VL domains. Similarly, amino acid variation is not precluded from amongst the genus of anti-TIM3 antibodies. Neither the specification nor the prior art provides guidance as to what structural changes can be made to the parent sequences for any one of the 10 clones and still predictably arrive at an anti-TIM3 antibody that binds TIM3 and internalizes the antigen within the RPMI 8226 cell line. The disclosed species therefore do not represent the claimed genus.
Has Applicant provided a common structure sufficient to visualize the genus?
Applicant has not provided a common structure sufficient to visualize the genus of all possible anti-TIM3 antibodies known-and yet to be discovered. While the disclosure provides the amino acid sequences of the 10 clones, there is no alignment between these and other TIM3 binders that might show similarities among their linear structures. One of ordinary skill in the art would have understood that the 10 clones functioned similarly, but would not have known which residues could have been replaced while still maintaining TIM3 binding and cellular internalization.
While the prior art contains disclosure as to the structural features of several anti- TIM3 antibodies, it is unclear what structural features these antibodies need to share in order to maintain binding affinity and stability. Even in 2021, functionalized antibodies are still not understood well enough to allow researchers to predict with certainty what modifications can be made to a primary antibody sequence such that binding is maintained. “[T]he major test of understanding is whether the changes associated with antibody maturation can be predicted with any reasonable accuracy, and whether there is sufficient information for developing therapeutic antibodies,” Vajda et al., “Progress toward improved understanding of antibody maturation,” Current Opinion in Structural Biology, 67 pp. 226-231 (2021 (PTO 892)) at p. 226, col. 2, lines 20-24.
As recently as 2020, researchers were still speculating as to how to reliably identify further putative binders from antibody sequence data, see, e.g., Marks et al., “How repertoire data are changing antibody science,” J. Biol. Chem. 295(29) 9823-9837 (2020 (PTO 892)), acknowledging that “there is a vast amount of the antibody sequence space that remains unknown,” p. 9831, col. 2, para. 2.
Even though the protein sequence of TIM3 is known in the art, this would not have translated into knowledge of the genus of antibodies that could possibly engage it much less facilitate cellular internalization. Computational and machine learning approaches for sequence-based prediction of paratope-epitope interactions are accumulating, but “it remains unclear whether antibody-antigen binding is predictable” (Akbar et al., Cell Reports 34, 108856, Mar. 16, 2021 at p. 2, col. 2, para. 2 (PTO 892)). The current state of the art continues to work toward finding an effective and efficient prediction tool for reliably assigning antibody structure based on known target epitopes. See e.g., Lo et al., “Conformational epitope matching and prediction based on protein surface spiral features,” BMC Genomics volume 22, Article number: 116 (2021 (PTO 892)) (disclosing new algorithms that calculate physicochemical properties, such as polarity, charge or the secondary structure of residues within the targeted protein sequences, and then applying quantitative matrix analyses or machine-learning algorithms to predict linear and conformational epitopes).
It is asserted that neither the specification nor the state of art at the time of filing disclosed structural features common to the members of the genus for reliably assigning different antibody structures based on sequence data for 10 antibody clones, which would support the premise that the inventors possessed the full scope of the claimed invention.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
9. Claim(s) 1 is/are rejected under 35 U.S.C. 102a1 as being anticipated by Takayanagi et al US 8552156 (IDS 3/20/2023).
This reference discloses monoclonal antibodies to TIM-3 and fragments thereof and these antibodies can be chimeric, humanized or human. The fragments can be Fab fragments (see summary, col. 11-31 and col. 32 and entire reference). ALSO SEE CLAIMS.
With respect to the limitation in claim 1, “induces internalization of TIM3 (in a FACS assay on TIM3 expressing RPM18226 cells (ATCC ® CCL-155TM)) of at least 45% after 120 Minutes at 37ºC”, since the reference and applicant are claiming the same antibody, it is inherent that the antibody of the reference has the same ability as the instant claimed amti-TIM3 antibody. Products of identical chemical composition cannot have mutually exclusive properties. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01. Since the Patent and Trademark Office does not have the facilities for examining and comparing the claimed hybridoma and antibody with the hybridoma and antibody of the reference, the burden of proof is upon the Applicants to show a distinction between the structural and functional characteristics of the claimed antibody and the antibody of the prior art. See In re Best, 562 F.2d 1252, 195 U.S.P.Q. 430 (CCPA 197) and Ex parte Gray, 10 USPQ 2d 1922 1923 (PTO Bd. Pat. App. & Int.).
10. Claim(s) 1 is/are rejected under 35 U.S.C. 102a1 as being anticipated by Kikushige et al Int. J. Hematol. Vol. 98 p. 627 (2013) (IDS 3/20/2023).
This reference discloses chimeric/humanized antibody ATIK2a which bind Tim-3 (page 629, second column, second full paragraph).
With respect to the limitation in claim 1, “induces internalization of TIM3 (in a FACS assay on TIM3 expressing RPM18226 cells (ATCC ® CCL-155TM)) of at least 45% after 120 Minutes at 37ºC”, since the reference and applicant are claiming the same antibody, it is inherent that the antibody of the reference has the same ability as the instant claimed amti-TIM3 antibody. Products of identical chemical composition cannot have mutually exclusive properties. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01. Since the Patent and Trademark Office does not have the facilities for examining and comparing the claimed hybridoma and antibody with the hybridoma and antibody of the reference, the burden of proof is upon the Applicants to show a distinction between the structural and functional characteristics of the claimed antibody and the antibody of the prior art. See In re Best, 562 F.2d 1252, 195 U.S.P.Q. 430 (CCPA 197) and Ex parte Gray, 10 USPQ 2d 1922 1923 (PTO Bd. Pat. App. & Int.).
11. Claim(s) 1 is/are rejected under 35 U.S.C. 102a1 as being anticipated by Wada et al WO 2010/084999 (IDS 3/20/2023) and Lippincott-Schwartz (Current Protocols in Cell Biology, 16.0.1-16.0.2, 2002) (IDS 3/20/2023).
This reference discloses anti-TIM3 antibodies (abstract and summary) that antibodies are human, humanized or chimeric or monoclonal or polyclonal (page 15+).
While Wada could not test their polyclonal antibodies for binding to the same epitope or competing with the claimed antibody, since polyclonal antibodies comprise a heterogeneous population of antibodies that bind the multiple immunogenic epitopes of an antigen, the polyclonal antibodies of Wada necessarily bind the same epitope and compete with the claimed antibodies. Notably, Wada teach making antibodies to the antigen which comprises the epitope, so antibodies to these epitopes would be formed.
Furthermore, as evidenced by Lippincott-Schwartz polyclonal antibodies are essentially a collection of monoclonal antibodies (see 16.0.1), so the antibodies of Wada also include monoclonal antibodies that bind these epitopes.
Therefore, the products of Wada are deemed to anticipate the claimed products absent a showing otherwise.
With respect to the limitation in claim 1, “induces internalization of TIM3 (in a FACS assay on TIM3 expressing RPM18226 cells (ATCC ® CCL-155TM)) of at least 45% after 120 Minutes at 37ºC”, and since the reference and applicant are claiming the same antibody, it is inherent that the antibody of the reference has the same ability as the instant claimed anti-TIM3 antibody. Products of identical chemical composition cannot have mutually exclusive properties. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01. Since the Patent and Trademark Office does not have the facilities for examining and comparing the claimed hybridoma and antibody with the hybridoma and antibody of the reference, the burden of proof is upon the Applicants to show a distinction between the structural and functional characteristics of the claimed antibody and the antibody of the prior art. See In re Best, 562 F.2d 1252, 195 U.S.P.Q. 430 (CCPA 197) and Ex parte Gray, 10 USPQ 2d 1922 1923 (PTO Bd. Pat. App. & Int.)
12. Claim(s) 1 is/are rejected under 35 U.S.C. 102a1 as being anticipated by Kuchroo et al WO 03/063792 (IDS 3/20/2023) and Lippincott-Schwartz (Current Protocols in Cell Biology, 16.0.1-16.0.2, 2002) (IDS 3/20/2023).
Kuchroo discloses antibodies which bind TIM-3 (abstract and summary) and these antibodies can be human, humanized or chimeric or monoclonal or polyclonal (summary, pages 7, 16-18). The reference also discloses fragments of these antibodies and states that the fragments are the fragments that are well known in the art (page 16-17). As evidenced by Lippincott-Schwartz polyclonal antibodies are essentially a collection of monoclonal antibodies (see 16.0.1), so the antibodies of Kuchroo also include monoclonal antibodies that bind these epitopes.
In this case, the Office does not have the facilities for examining and comparing Applicant's products with the products of the prior art in order to establish that the products of the prior art possess the same material, structural, and functional characteristics as Applicant’s products. In the absence of evidence to the contrary, the burden is upon the applicant to prove that the products to which the claims are directed are different than that taught by the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA, 1977) and Ex parte Gray, 10 USPQ2d 1922 1923 (PTO Board of Patent Appeals and Interferences, 1988 and 1989).
Therefore, the products of Kuchroo are deemed to anticipate the claimed products absent a showing otherwise.
With respect to the limitation in claim 1, “induces internalization of TIM3 (in a FACS assay on TIM3 expressing RPM18226 cells (ATCC ® CCL-155TM)) of at least 45% after 120 Minutes at 37 ºC”, and since the reference and applicant are claiming the same antibody, it is inherent that the antibody of the reference has the same ability as the instant claimed anti-TIM3 antibody. Products of identical chemical composition cannot have mutually exclusive properties. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01. Since the Patent and Trademark Office does not have the facilities for examining and comparing the claimed hybridoma and antibody with the hybridoma and antibody of the reference, the burden of proof is upon the Applicants to show a distinction between the structural and functional characteristics of the claimed antibody and the antibody of the prior art. See In re Best, 562 F.2d 1252, 195 U.S.P.Q. 430 (CCPA 197) and Ex parte Gray, 10 USPQ 2d 1922 1923 (PTO Bd. Pat. App. & Int.).
13. Claim(s) 1 is/are rejected under 35 U.S.C. 102a1 as being anticipated by Karsunky et al WO 2013/006490 (IDS 3/20/2023) and Lippincott-Schwartz (Current Protocols in Cell Biology, 16.0.1-16.0.2, 2002) (IDS 3/20/2023).
Karsunky discloses antibodies which bind TIM-3 (abstract and summary and entire reference) and these antibodies can be human, humanized or chimeric or monoclonal or polyclonal (summary, paragraphs 67-68, 73, 120 and 123). The reference also discloses fragments of these antibodies and specifically recites Fab fragments (paragraph 67). As evidenced by Lippincott-Schwartz polyclonal antibodies are essentially a collection of monoclonal antibodies (see 16.0.1), so the antibodies of Karsunky include monoclonal antibodies that bind these epitopes.
The Office does not have the facilities for examining and comparing Applicant's products with the products of the prior art in order to establish that the products of the prior art possesses the same material, structural, and functional characteristics as Applicant’s products. In the absence of evidence to the contrary, the burden is upon the applicant to prove that the products to which the claims are directed are different than that taught by the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA, 1977) and Ex parte Gray, 10 USPQ2d 1922 1923 (PTO Board of Patent Appeals and Interferences, 1988 and 1989).
Therefore, the products of Karsunky are deemed to anticipate the claimed products absent a showing otherwise.
With respect to the limitation in claim 1, “induces internalization of TIM3 (in a FACS assay on TIM3 expressing RPM18226 cells (ATCC ® CCL-155TM)) of at least 45% after 120 Minutes at 37ºC”, and since the reference and applicant are claiming the same antibody, it is inherent that the antibody of the reference has the same ability as the instant claimed anti-TIM3 antibody. Products of identical chemical composition can not have mutually exclusive properties. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01. Since the Patent and Trademark Office does not have the facilities for examining and comparing the claimed hybridoma and antibody with the hybridoma and antibody of the reference, the burden of proof is upon the Applicants to show a distinction between the structural and functional characteristics of the claimed antibody and the antibody of the prior art. See In re Best, 562 F.2d 1252, 195 U.S.P.Q. 430 (CCPA 197) and Ex parte Gray, 10 USPQ 2d 1922 1923 (PTO Bd. Pat. App. & Int.).
Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957). A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
14. Claim 1 of this application is patentably indistinct from claim 1 of Application No. 18/600,323. Pursuant to 37 CFR 1.78(f), when two or more applications filed by the same applicant or assignee contain patentably indistinct claims, elimination of such claims from all but one application may be required in the absence of good and sufficient reason for their retention during pendency in more than one application. Applicant is required to either cancel the patentably indistinct claims from all but one application or maintain a clear line of demarcation between the applications. See MPEP § 822.
Claim 1 is provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claim 1 of copending Application No. 18/600,323 (reference application US 20240270844). This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
15. Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3 of U.S. Patent No. 10287352 (IDS of 3/20/2023) as evidenced by the specification. The reference patent is not afforded safe harbor protection under 35 USC 121 because it shares no continuity nor a 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. Specifically, the claims of the instant invention are directed to anti-TIM3 antibodies. The patent claims are directed to bispecific antibodies that bind to TIM3 and PD1 and compositions thereof. The TIM3 portion of the ref bispecific antibody reads on and anticipates and/or renders obvious the instant claimed TIM3 antibodies. For example, the instant disclosure for SEQ ID NO. 7 is the same as patent claim SEQ ID NO. 7 of claim 3. The instant disclosure for SEQ ID NO. 8 is the same as patent claim SEQ ID NO. 8 and 10 of claim 3. Thus, the anti-TIM3 antibodies of the patent claims anticipate and render the claimed generic invention obvious for at least
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, where Tim3_0016 meets the functional criteria of instant claim 1:
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16. Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3 of U.S. Patent No. 11130810 as evidenced by the specification. The reference patent is not afforded safe harbor protection under 35 USC 121 because it shares no continuity nor a 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. Specifically, the claims of the instant invention are directed to anti-TIM3 antibodies. The patent claims are directed to bispecific antibodies that bind to TIM3 and PD1 and compositions thereof. The TIM3 portion of the ref bispecific antibody reads on and anticipates and/or renders obvious the instant claimed TIM3 antibodies. For example, the instant disclosure for SEQ ID NO. 7 is the same as patent claim SEQ ID NO. 7 of claim 3. The instant disclosure for SEQ ID NO. 8 is the same as patent claim SEQ ID NO. 8 and 10 of claim 3. Thus, the anti-TIM3 antibodies of the patent claims anticipate and render the claimed generic invention obvious for at least
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, where Tim3_0016 meets the functional criteria of instant claim 1:
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17. Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3 of U.S. Patent No. 12391757 as evidenced by the specification. The reference patent is not afforded safe harbor protection under 35 USC 121 because it shares no continuity nor a 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. Specifically, the claims of the instant invention are directed to anti-TIM3 antibodies. The patent claims are directed to bispecific antibodies that bind to TIM3 and PD1 and compositions thereof. The TIM3 portion of the ref bispecific antibody reads on and anticipates and/or renders obvious the instant claimed TIM3 antibodies. For example, the instant disclosure for SEQ ID NO. 7 is the same as patent claim SEQ ID NO. 7 of claim 3. The instant disclosure for SEQ ID NO. 8 is the same as patent claim SEQ ID NO. 8 and 10 of claim 3. Thus, the anti-TIM3 antibodies of the patent claims anticipate and render the claimed generic invention obvious for at least
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72
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, where Tim3_0016 meets the functional criteria of instant claim 1:
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Conclusion
18. No claims are allowed.
19. 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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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.
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LYNN ANNE BRISTOL
Primary Examiner
Art Unit 1643
/LYNN A BRISTOL/Primary Examiner, Art Unit 1643