DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims Status
The preliminary amendment filed 11/13/2023 has been entered. Claims 1-20 are pending and under examination. Claims 3-7 and 9-10 are amended. Claims 12-20 are new.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
However, CN202011301761.2, filed 11/19/2020, is not a certified English translation. Therefore, the claims are examined with the filing date of 11/18/2021 of PCT/CN2021/131542. Therefore, the effective filing date for claims 1-20 is 11/18/2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 11/13/2023 and 12/23/2024 was filed. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
The information disclosure statement filed 5/17/2023 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered.
Nucleotide and/or Amino Acid Sequence Disclosures
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 2-3 rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 2-3 identify antibody variable chain sequences or light and heavy chain sequences by SEQ ID NO, respectively, or a sequence having 80% identity to the sequence, or a sequence having one or more conservative amino acid substitutions. Claim 2 and 3 depends on claim 1, which identifies the six total heavy and light chain CDR sequences. Based on the number of amino acids in all six CDRS sequences and the number of amino acids in the variable heavy and light chain sequences in claim 2, it would not be possible to have only 80% sequence match if all the CDRs sequences in parent claim 1 are retained. Regarding both claim 2 and 3, if the conservative amino acid substitution is in one of the CDR regions, then it does not comprise the sequences in parent claim 1. Therefore, claim 2 and 3 fails to include all the limitations of claim 1, upon which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Written Description
Claims 1-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention.”
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the Applicants were in possession of the claimed genus.
The claims are directed towards a method for treating a tumor or cancer, comprising administering to a patient in need thereof an effective amount of an anti-0X40 antibody or an antigen- binding fragment thereof. Tumors and cancers are genus of pathology and diseases that comprises of specific species of tumors and cancers, respectively. The claims further direct to treating specific cancers.
The anti-OX40 antibody in the method comprises CDR sequences set forth in the claims by SEQ ID NO. The anti-OX40 antibody in the method also comprises of paired VH and VL sequences, and paired heavy and light chain sequences defined in the claim by SEQ ID NO, or a sequence that has 80% identity to these sequences. The claimed antibodies therefore represent a genus of antibodies comprising of species comprising of different sequences from one another. The claims also encompass mutations in the heavy and light chain, which are in both the Fab and Fc region of the antibody.
The claims are further directed to fucosylation level of the anti-OX40 antibody antigen-binding fragment thereof and the expression of the anti-OX40 antibody or antigen-binding fragment thereof by a cell with the α-(1,6)-fucosyltransferase gene knocked out.
The claims also disclose ranges of the effective amount, dose, administration routes, treatment cycle, and the dosing frequency of the anti-OX40 antibody. The claims are also directed towards a kit comprising an anti-OX40 antibody or antigen-binding fragment and an instruction for directing administration of the anti-0X40 antibody or the antigen- binding fragment to a patient in need thereof, wherein the antibody comprises the sequences set forth in the claim. Therefore, the invention requires specific instructions for directing administration for the claimed antibody or an antigen-binding fragment thereof to a patient.
Regarding the treatment of tumor or cancer with the claimed anti-OX40 antibodies, the specification discloses a method of decreasing tumor volume for one specific tumor line using one specific species of anti-OX40 antibody.
The specification does not disclose reduction to practice of any other species of antibody or treating other tumors or cancers. The specification is silent on the correlation between structure and function of the other claimed species of antibody. The specification is silent on whether the other species of antibodies have anti-tumor effects as the one species of antibody reduced to practice. The specification is silent on how representative the example tumor is of every other tumor or cancer in the claims, or all tumors or cancers in general. Therefore, the specification provides insufficient written description to support the entire scope of the genus of tumors and cancers encompassed by the claims.
Regarding the claimed fucosylation level and generation of the antibody or antigen-binding fragment thereof used in the method, the specification is met for the expression of antibodies with fucosulation level of 0%-10% by a cell with the α-(1,6)-fucosyltransferase gene knocked out, as is described using the CHO-BAT-KF cells disclosed.
Regarding the claimed administration parameters and the kit comprising of instructions for directing administration of the claimed antibody, the specification discloses broad ranges and list of potential values for the effective amounts, dose, treatment cycle, dosing frequency, and administration routes for the anti-OX40 antibodies in the method. Without guidance of how to combine the parameters, the broad ranges of doses, dosing frequency, and treatment cycles claimed can be combined to be directed towards a large amount of possible parameter combinations. The claims require that a method using each of these administration parameters for the claimed antibody have the claimed function of treating cancer and tumors. In regards to the kit, the specification teaches a kit comprising of an anti-OX40 antibody and instruction for directing administration of the antibody to a patient in need thereof, wherein in one embodiment, the antibody is antibody M-KF which was expressed by a cell line in which the α-(1,6)-fucosyltransferase gene was knocked out.
However, the specification reduces to practice only a limited number of administration examples, as described in Examples 2-4, that does not fully encompass the broad ranges claimed. that the applicants do not show possession of. The specification is silent on the correlation of effects seen at one set parameter on effects at other parameters. For example, example 2 teaches anti-tumor effect at 1 mg/kg and 0.04 mg/kg in mice models, and example 4 teaches the highest non-severely toxic dose in this experiment was considered to be 30 mg/kg. The claimed range for administration dose spans 0.01 mg/kg to 25 mg/kg (claim 9) but there is no indication whether higher doses, although not toxic, is still therapeutically effective. Regarding the instructions in the kit, despite the list of potential values for administration parameters disclosed, the specification lacks specific instructions for administration to a patient. One of ordinary skill in the art cannot envision the instructions for administration simply from a list of potential administration parameter values without guidance on how to choose which values. Therefore, the specification provides insufficient written description to support the entire scope of parameters and instructions in the claims. Adequate written description requires more than a mere statement that the feature is part of the invention.
Regarding the treatment of the encompassed tumors and cancers in the method, the state of the art teaches tumors and cancers are known be diverse pathologies and diseases and it is generally known that one species of antibody cannot treat every cancer or tumor. Furthermore, the relevant state of the art teaches that although there have been some preclinical anti-tumor effects that motivate clinical studies, these preclinical anti-tumor effects do not translate to clinical response in clinical trials in cancer patients and any responses are limited and low clinical responses (Redmond, W., et al, Challenges and opportunities in the development of combination immunotherapy with OX40 agonists, Expert Opin Biol Ther. 2023 Aug 20;23(9):901–912, published 08/20/2024, hereafter referred to as Redmond et al. Section 3, paragraph 1). Redmond et al teaches that trials with anti-OX40 antibodies disclosed in Table 1 showed no significant treatment effect for breast cancer, prostate cancer, myeloid leukemia, and other advanced solid tumors and blood cancers. The state of the art teaches that because of these limited efficacies of OX40 agonist monotherapy, most ongoing clinical trials with OX40 agonists are for combination therapy comprising of OX40 agonists with other immune modulating agent candidates. However, the responses from combination therapy with these OX40 agonists are not different from the responses from monotherapy of the other agent in the combination, meaning that OX40 agonists added no effects (section 3.1 paragraph 2). Some hypothesis to explain the lack of clinical activity of these OX40 agonists is limitation to the monoclonal antibody agents themselves (section 3.1, paragraph 3). Further, Thapa et al teaches that OX40 expression is variable between tumors and that patterns of expression theoretically most suitable for OX40 agonists only occurs in 17% of cancer patients, mostly in lung and breast cancer (Thapa, B., et al, OX40/OX40 ligand and its role in precision immune oncology, Cancer and Metastasis Reviews, 43:1001-1013, published 03/25/2024; hereafter referred to as Thapa et al. Page 1010). These references demonstrate the inability of OX40 monoclonal antibodies to treat all the tumors and cancers claimed.
With the state of the art teaching specific OX40 agonist monoclonal antibodies that have failed in treating cancers, despite anti-tumor effects in preclinical trials, no teachings in the specification linking the anti-tumor effects of this specifically claimed antibody to treating cancer, and no teaching in the specification on how this particularly claimed anti-OX40 antibody is effectively different from currently known anti-OX40 antibodies, one skilled in the art cannot reasonably conclude that anti-tumor effect in one tumor model is sufficient to treatment of other tumors or cancers. Thus, one skilled in the art cannot reasonably conclude that the applicant is in possession of an antibody that could treat all tumors or cancers claimed.
Regarding the encompassed antibodies and antigen-binding fragments thereof in the method, the state of the art teaches protein and antibody engineering is one of the most unpredictable areas of biotechnology. This unpredictability prevents prediction of the effects that a given number of mutations will have on an antibody or protein. Therefore, even given the sequence of an antibody, without sufficient written description of its function, the state of the art teaches its function is unpredictable. Specifically regarding antibodies, the state of the art teaches the CDR plays a key role in the target affinity of an antibody, showing that even a single amino acid alteration in the CDR can result in loss of antigen-binding function (Rudikoff, S., et al, Single amino acid substitution altering antigen-binding specificity, Proc. Natl. Acad. Sci., Vol 79, pp 1979-1983, published 03/1982; hereafter referred to as Rudikoff et al.). The state of the art further teaches that even minor changes in the amino acid sequences of the heavy and light chain variable regions, even outside the CDR, can affect the antibody function, including affinity (Wang, S., et al, Precision engineering of antibodies: A review of modification and design in the Fab region, International Journal of Biological Macromolecules, 275 (2024) 133730; hereafter referred to as Wang et al, 2024. Introduction). The claims also encompass mutations in the heavy and light chain, which are in both the Fab and Fc region of the antibody. Although Fc modifications may have less impact on target affinity, these changes significantly alter other key biological functions important to the antibody’s therapeutic potential and stability (Wang et al, 2024, Introduction). These references demonstrate that even a single amino acid substitution will often dramatically affect the biological activity and characteristics of antibody.
With the state of the art teaching the unpredictability of antibody function based on sequence and that even minor mutations outside of the CDRs and especially within the CDRs can affect antibody function; and insufficient disclosure in the specification on the function of each species of antibodies, with only one species reduced to practice, and insufficient guidance on which particular sequences could possibly be changed to maintain desired function, one skilled in the art cannot reasonably conclude that the other antibodies claimed will have the same anti-tumor effect as the antibody reduced to practice, or be able to predict any function of the antibody. Thus, one skilled in the art cannot reasonably conclude that the applicant is in possession of a method to treatment cancers or tumors comprising of the entire scope of claimed antibodies. With the lack of a representative number of species across the breadth of the genus, one of skill in the art would not reasonably conclude that the full breadth of the claims meet the written description provision of 35 USC 112(a).
Regarding the claimed administration parameters, such as treatment cycle, dose, and effective amount, and instructions for administration included in the kit, the state of the art teaches that administration parameters for OX40 agonists in clinical trials are variable (Thapa et al, section Development of drugs targeting OX40 and OX40L for cancer treatment). In other words, not all anti-OX40 antibodies have the same administration parameters and the set of parameters that allow one anti-OX40 antibody to work is not the same for other anti-OX40 antibody. Thapa et al teaches that in a clinical trial for the OX40 agonist, Ivuxolimab, although there was anti-tumor response at one of the lower doses tested, higher doses led to diminished anti-tumor response (page 1007), hypothesized to be possibly due to T cell exhaustion at high OX40 agonist dose. Related to this, Wang et al, 2019 teaches that OX40 receptor occupancy between 20% and 50% both in vitro and in vivo was associated with maximal enhancement of T-cell effector function, which implies that higher doses from an effective dose does not always lead to higher function (Wang, R., et al, An Integrative Approach to Inform Optimal Administration of OX40 Agonist Antibodies in Patients with Advanced Solid Tumors, Clin Cancer Res 2019;25:6709–20, published 11/15/2019; hereafter referred to as Wang et al, 2019. Abstract). The treatment cycle and effective amounts are all dependent on the dose, and therefore, the broad claimed ranges of these parameters also cannot be assumed to work if treatment was shown to be successful for select parameters were validated. It is generally well-known in the art that it cannot be assumed if higher doses have therapeutic effects, lower doses will too. These references teach that it cannot be assumed that if a lower dose of OX40 agonist had anti-tumor effects, higher doses will too.
With the state of the art teaching that the effects of one administration parameter does not imply the same effect for higher or lower values of parameters and insufficient working examples using the entire scope of the claimed inventions, one of ordinary skill in the art would understand that the species of administration parameter disclosed cannot represent the entire breadth of administration parameter claimed and would not reasonably conclude that the full breadth of the claims meet the written description provision of 35 USC 112(a).
The University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 held that: …To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines Inc. 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2dat1966.
MPEP § 2163.02 states, “[a]n objective standard for determining compliance with the written description requirement is, 'does the description clearly allow person of ordinary skill in the art to recognize that he or she invented what is claimed’”. The courts have decided: the purpose of the "written description" requirement is broader than to merely explain how to "make and use"; the applicant must convey with reasonable clarity to those skilled in the art, that as of the filing date sought, he or she was in possession of the invention. The invention is for purposes of the “written description” inquiry, whatever is now claimed. See Vas-Cath, Inc v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991). However, factual evidence of an actual reduction to practice for the full scope of the claimed invention has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has the Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed. Furthermore, the written description provision of 35 USC §112 is severable from its enablement provision.
For all these reasons, the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that applicant had possession of the invention, as claimed in claims 1-20, at the time the instant application was filed.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-6, 9, and 12-15 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Liang et al (US 2023/0139700 A1; Development and Application of Immune Cell Activator; Effectively filed: 03/23/2020; Published: 05/04/2023, hereafter referred to as Liang et al).
The applied reference has a common assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Regarding instant claim 1 and 2, Liang et al teaches a method of treating a cancer in a patient in need, comprising of administering to the patient an effective dose of an anti-OX40 antibody or fragment thereof (paragraph 77) comprising of the variable heavy chain sequence of SEQ ID NO: 72 and variable light chain sequence of SEQ ID NO: 84 (claim 5 and paragraph 47). These variable heavy chain sequence and variable light chain sequence have 100% sequence match to the instant variable heavy chain sequence of instant SEQ ID NO:7 and variable light chain sequence of instant SEQ ID NO:8, respectively in instant claim 2. The variable heavy chain sequence comprises of the instant CDRS of instant SEQ ID NO: 1-3 in instant claim 1 and the variable light chain sequence comprises of the instant CDRS of SEQ ID NO: 4-6 in instant claim 1, with 100% sequence match.
Regarding instant claim 3, Liang et al teaches an OX40 antibody comprising of the heavy chain of SEQ ID NO: 86 and light chain of SEQ ID NO: 87 (claim 7 and paragraph 58), which have 100% sequence match to the instant heavy chain of instant SEQ ID NO: 9 and instant light chain of instant SEQ ID NO: 10.
Regarding instant claim 4, Liang et al teaches the content of fucose is no more than 10% (paragraph 69; and Example 8, paragraph 222), which is identical to the instantly claimed 0-10% fucosylation.
Regarding instant claim 5, Liang et al teaches the antibody was expressed by CHO cell line in which the fut8 gene, which is an a-(1,6)-fucosyltransferase gene, was knocked out (paragraph 67 and 222).
Regarding instant claim 6, Liang et al teaches the disorders that can be treated by the anti-OX40 antibody comprises all the cancers listed in instant claim 6 (paragraph 186).
Regarding instant claims 9 and 12-15, Liang et al teaches administration doses of:
0.04 mg/kg, 0.2 mg/kg, 1 mg/kg (paragraph 226); or
about 0.01 mg/kg to about 100 mg/kg (paragraph 187); or
about 0.1 mg/kg to about 30 mg/kg (paragraph 219); or
3 mg/kg (paragraph 187);
which fall within the instantly claimed dose ranges of the anti-OX40 antibody or the antigen-binding fragment for each administration.
Thus, Liang et al (US 2023/0139700 A1) anticipates instant claims 1-6, 9, and 12-15.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 7-8 and 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Liang et al (US 2023/0139700 A1; Development and Application of Immune Cell Activator; Effectively filed: 03/23/2020; Published: 05/04/2023, hereafter referred to as Liang et al).
The applied reference has a common assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
The teachings of Liang et al as related to instant claim 1, from which these claims depend are given previously in this Office Action and incorporated here.
Liang et al does not explicitly teach in one embodiment the effective amount of the anti-OX40 antibody or antigen binding fragment. Liang also does not explicitly teach the treatment cycle or administration frequency of the antibody or antigen binding fragment.
Regarding effective amount, related to claims 7, 16-18, and 20, Liang et al teaches antibody administration doses, which are given in units of mg/kg. Liang teaches administration doses of:
0.04 mg/kg, 0.2 mg/kg, 1 mg/kg (paragraph 226); or
about 0.1 mg/kg to about 30 mg/kg (paragraph 219); or
3 mg/kg (paragraph 187).
Furthermore, Liang et al teaches that a therapeutically effective amount of the antibody described herein relates to an amount required to achieve a therapeutic goal, which depends on a variety of factors. Liang teaches that a therapeutically effective amount depends on the binding affinity of the antibody for its antigen, the disease severity, administration route, and the rate of antibody depletion in the patient (paragraph 187). Therefore, the effective amount may depend on the weight of the subject. These disclosures teach that the effective dose of the antibody or antigen binding fragment is a result-effective variable that a person of ordinary skill in the art would routinely optimize in methods of treatment using an antibody or antigen binding fragment.
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the instant application, to use the administration doses taught by Liang et al to calculate the effective amount for a subject, based on the subject’s weight. The effective amounts calculated from the disclosed effective doses and reasonable weights for adult humans is within the range of instantly claimed effective amounts. One of ordinary skill in the art would have understood that since these doses were optimized for effectiveness and safety, the effective amounts derived from them would have had a reasonable expectation of success. Thus, using the doses to calculate effective amount is the purpose of the doses being reported in units of mg/kg.
Since effective dose of the antibody or antigen binding fragment is a result-effective variable that a person of ordinary skill in the art would routinely optimize in methods of treatment using an antibody or antigen binding fragment, differences in ranges of result-effective variables between the art and instant application are not novel and are a matter of routine optimization. The principle of law states from MPEP §§ 2144.05: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages," (see In re Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382). Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation," (See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)).
Regarding administration frequency, related to claims 8 and 19-20, Liang et al teaches that administration frequency may be once every two weeks or once every three weeks (paragraph 187). Administration frequency is related to effective dosing since the frequency can change depending on the dose. Again, Liang teaches that a therapeutically effective amount depends on the binding affinity of the antibody for its antigen, the disease severity, administration route, and the rate of antibody depletion in the patient (paragraph 187). The rate of antibody depletion in the patient varies amongst patients. As such, the administration frequency of the antibody or antigen binding fragment is a result-effective variable that a person of ordinary skill in the art would routinely optimize in methods of treatment using an antibody or antigen binding fragment.
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the instant application, to use the administration frequency taught by Liang, for the same antibody as the claimed invention. One of ordinary skill in the art would have had a reasonable expectation of success since the same antibody as the instantly claimed antibody was used in the same tumor model as the instant application.
Since the administration frequency of the antibody or antigen binding fragment is clearly a result-effective variable that a person of ordinary skill in the art would routinely optimize in methods of treatment using an antibody or antigen binding fragment, differences in ranges of result-effective variables between the art and instant application are not novel and are a matter of routine optimization. The principle of law states from MPEP §§ 2144.05: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages," (see In re Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382). Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation," (See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)).
Claims 10 are rejected under 35 U.S.C. 103 as being unpatentable over Liang et al (US 2023/0139700 A1; Development and Application of Immune Cell Activator; Effectively filed: 03/23/2020; Published: 05/04/2023, hereafter referred to as Liang et al) as applied to claims 7-8 and 16-20 above, and further in view of Bittner et al (Bittner, B., et al, Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities, BioDrugs (2018) 32:425–440, published 07/24/2018 ; hereafter referred to as Bittner et al).
The teachings of Liang et al as related to instant claim 1, from which these claims depend are given previously in this Office Action and incorporated here.
Liang et al teaches intraperitoneal administration of the anti-OX40 antibody into mice tumor models. Liang et al does not explicitly teach in one embodiment intravenous injection and subcutaneous injection as administration routes, as in instant claim 10.
However, Liang et al does teach that for pharmaceutical compositions for humans, examples of administration routes include intravenous, intradermal, subcutaneous, oral (e.g. inhalation), transdermal (i.e. topical), transmucosal, and rectal administration (paragraph 196). Bittner et al teaches that intravenous administration of biotherapeutics is most typical in the clinic, but subcutaneous injections have been shown to be a safe, efficacious, and cost-effective dosing alternative valued by both patients and healthcare professionals because it can be administered at home (Abstract). Most approved antibodies are for intravenous or subcutaneous injections. Although some have been developed for intramuscular injections, new versions of the drug have been developed for subcutaneous injection (Bittner et al, section Recent Advances in Subcutaneous Biotherapeutic Administration, pages 427-428). One skilled in the art would understand that when translating the mice experiments to human subjects, one would not use an intraperitoneal injection. One would be motivated to try other administration routes, selected from a list of finite number of administration routes more common and suitable for human subject. Intravenous injection and subcutaneous injection are identified and predictable potential solutions for administering biotherapeutics, especially antibodies, to human patients. Therefore, one of ordinary skill in the art would have had a reasonable expectation of success using these administration routes for treating human patients even without mouse trials with these administration routes. It is common for mouse trials with the antibody to use an administration route suitable for mouse without dictating the administration routes for humans.
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses that choosing from a finite number of identified, predictable solutions, with reasonable expectation of success, is obvious. Liang teaches a finite list of administration routes for human patients and Bittner et al teaches the most common two for the delivering biotherapeutics, such as antibodies, to humans. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Claims 11 are rejected under 35 U.S.C. 103 as being unpatentable over Liang et al (US 2023/0139700 A1; Development and Application of Immune Cell Activator; Effectively filed: 03/23/2020; Published: 05/04/2023; hereafter referred to as Liang et al) as applied to claims 7-8 and 16-20 above, and further in view of Kato et al (US 8283450 B2; Human Monoclonal Antibody Human CD134 (OX40) and Methods of Making and Using the Same; Effectively filed: 11/25/2005; hereafter referred to as Kato et al).
The teachings of Liang et al as related to the sequence of the antibody contained in the kit of instant claim 11 are given previously in this Office Action and incorporated here. Liang teaches that the antibody can be used as a reagent in a diagnostic kit.
Liang et al does not explicitly teach the antibody could be used in a kit with instructions for administering the antibody to a patient in need thereof.
Kato et al teaches a kit including an anti-0X40 antibody, subsequence or fragment, and instructions for treating a subject in need of treatment with the OX40 antibody, subsequence or fragment (column 36, lines 38-43).
One of ordinary skill in the art would be motivated to substitute the anti-OX40 antibody taught by Liang into the kit comprising of another anti-OX40 antibody taught by Kato et al.
One would be motivated to substitute the anti-OX40 antibody taught by Liang et al into the kit taught by Kato et al because this antibody has shown anti-tumor effects and has therapeutic potential. Putting it inside a kit with instructions for its use in treating patients would be an obvious end goal for this antibody. One of ordinary skill in the art would have had a reasonable expectation of success because the kit taught by Kato et al is not specific to the specific anti-OX40 antibody taught by Kato et al, but would be routinely optimized for the particular anti-OX40 antibody that it comprises, as it emphasizes the need for suitable packaging, instructions for satisfactory clinical endpoints or adverse complications, buffering agents, preservatives, or a stabilizing agent (column 36, line 49 – column 37, line 13).
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses a simple substitution of one known element for another to obtain predictable results is obvious. Liang et al teaches an anti-OX40 antibody with anti-tumor effects whereas Kato et al teaches that anti-OX40 antibodies that have therapeutic potential put into kits with instructions for their use in the treatment of patients in need thereof. It would be obvious to substitute the anti-OX40 antibody of Liang et al into the kit taught by Kato et al. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Statutory Double Patenting
Application No. 19166027
Instant claim 11 of this application is patentably indistinct from claim 13 of copending Application No. 19166027 (hereafter referred to as Liang ‘027). Both claims are directed to a kit comprising an anti-OX40 antibody or an antigen-binding fragment and instructions for directing administration of the antibody or fragment to a patient in need thereof, wherein the antibody or fragment comprises of the six CDR sequences also in instant claim 11. Instant SEQ ID NO: 1-6 have a 100% match to SEQ ID NO: 1-6, respectively, in claim 13.
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.
Instant claim 11 is directed to the same invention as that of claim 13 of commonly assigned copending Application No. 19166027. Under 35 U.S.C. 101, more than one patent may not be issued on the same invention.
The USPTO may not institute a derivation proceeding in the absence of a timely filed petition. The U.S. Patent and Trademark Office normally will not institute a derivation proceeding between applications or a patent and an application having common ownership (see 37 CFR 42.411). The applicant should amend or cancel claims such that the reference and the instant application no longer contain claims directed to the same invention.
Nonstatutory 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.
Application No. 17913429
Instant claims 1-9, 12-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 9-11, 15-16 of copending Application No. 17913429 (claims filed 03/23/2023, hereafter referred to as Liang ‘429). Although the claims at issue are not identical, they are not patentably distinct from each other because. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding instant claim 1, copending reference Liang ‘429 claim 1-2 teaches an anti-OX40 antibody comprising of VH CDR and VL CDR sequences selected from a list that includes CDR sequences that match 100% with instant claim 1, and claim 3 teaches the exact combination of CDR sequences in instant claim 1. Instant SEQ ID NOs: 1-6 are 100% identical to SEQ ID NOs: 10, 26, 27, 61, 25, and 34, respectively. Claim 15 teaches a method for treating a cancer in a patient in need thereof, comprising of administering to the patient an effective dose of the anti-OX40 antibody or the fragment thereof.
Regarding instant claim 2, copending reference Liang ‘429 claim 4 teaches an anti-OX40 antibody comprising of VH and VL sequences, and claim 5 teaches the exact combination of VH and VL sequences in instant claim 2. Instant SEQ ID NOs: 7-8 are 100% identical to SEQ ID NOs: 72 and 84, respectively. Claim 15 teaches a method for treating a cancer in a patient in need thereof, comprising of administering to the patient an effective dose of the anti-OX40 antibody or the fragment thereof.
Regarding instant claim 3, copending reference Liang ‘429 claim 6 teaches an anti-OX40 antibody comprising of heavy chain and light chain sequences, and claim 7 teaches the exact combination of heavy chain and light chain sequences in instant claim 3. Instant SEQ ID NOs: 9-10 are 100% identical to SEQ ID NOs: 86 and 87, respectively. Claim 15 teaches a method for treating a cancer in a patient in need thereof, comprising of administering to the patient an effective dose of the anti-OX40 antibody or the fragment thereof.
Regarding instant claim 4, copending reference Liang ‘429 claim 9 teaches an anti-OX40 antibody and fragment thereof wherein the content of fucose in the antibody is no more than 10% and claim 11 teaches the fucose content is 0%, which matches the fucosylation level of 0% to 10% in instant claim 4. Claim 15 teaches a method for treating a cancer in a patient in need thereof, comprising of administering to the patient an effective dose of the anti-OX40 antibody or the fragment thereof.
Regarding instant claim 5, copending reference Liang ‘429 claim 10 teaches an anti-OX40 antibody and fragment thereof wherein the antibody is expressed in a CHO cell in which a fut8 gene is knocked out, which is a a-(1,6)-fucosyltransferase gene relevant to instant claim 5. Claim 15 teaches a method for treating a cancer in a patient in need thereof, comprising of administering to the patient an effective dose of the anti-OX40 antibody or the fragment thereof.
Regarding instant claim 6, copending reference Liang ‘429 claim 15 teaches a method for treating cancer in a patient in need thereof, comprising of administering to the patient an effective dose of the anti-OX40 antibody or the fragment thereof. Claim 16 further teaches that the cancer is selected from a list of cancers provided, which match the list of cancers in instant claim 6.
Regarding instant claims 7-9, 12-20, copending reference Liang ‘429 claim 15 teaches a method for treating cancer in a patient in need thereof, comprising of administering to the patient an effective dose of the anti-OX40 antibody or the fragment thereof. Liang ‘429 claims do not explicitly teach the exact same dose, effective amount, administration frequency, and treatment cycles for the anti-OX40 antibody or fragment in this method. However, one of ordinary skill in the art would recognize that these are all result-effective variables that a person of ordinary skill in the art would routinely optimize in methods of treatment using an antibody or antigen binding fragment. Liang ‘429 teaches that a therapeutically effective amount of the antibody described herein relates to an amount required to achieve a therapeutic goal, which depends on a variety of factors. Liang teaches that a therapeutically effective amount depends on the binding affinity of the antibody for its antigen, the disease severity, administration route, and the rate of antibody depletion in the patient (paragraph 187). Therefore, the effective amount may depend on the weight of the subject. These disclosures teach that the effective dose of the antibody or antigen binding fragment is a result-effective variable that a person of ordinary skill in the art would routinely optimize in methods of treatment using an antibody or antigen binding fragment. The specification of the reference application provides example values for each parameter or parameters that can be used to calculate the parameters (US 2023/0139700 A1, page 16, paragraphs 187).
Administration frequency is related to effective dosing since the frequency can change depending on the dose. Again, Liang teaches that a therapeutically effective amount depends on the binding affinity of the antibody for its antigen, the disease severity, administration route, and the rate of antibody depletion in the patient (paragraph 187). The rate of antibody depletion in the patient varies amongst patients. As such, the administration frequency of the antibody or antigen binding fragment is a result-effective variable that a person of ordinary skill in the art would routinely optimize in methods of treatment using an antibody or antigen binding fragment.
It would have been prima facie obvious to one of ordinary skill in the art to use the administration doses and frequency taught by Liang ‘429, for the same antibody as the claimed invention. One of ordinary skill in the art would have had a reasonable expectation of success since the same antibody as the instantly claimed antibody was used in the same tumor model as the instant application.
Since the administration parameters are result-effective variables, differences in ranges of result-effective variables between the reference and instant application are not novel and are a matter of routine optimization. The principle of law states from MPEP §§ 2144.05: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages," (see In re Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382). Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation," (See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)).
Instant claim 10 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 15 of copending Application No. 17913429 (claims filed 03/23/2023) in view of Bittner et al. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding instant claim 10, copending reference Liang ‘429 claim 15 teaches a method for treating cancer in a patient in need thereof, comprising of administering to the patient an effective dose of the anti-OX40 antibody or the fragment thereof.
Liang ‘429 does not explicitly teach in one embodiment intravenous injection and subcutaneous injection as administration routes for treating cancer, as in instant claim 10.
However, Liang does teach that for pharmaceutical compositions for humans, examples of administration routes include intravenous, intradermal, subcutaneous, oral (e.g. inhalation), transdermal (i.e. topical), transmucosal, and rectal administration (paragraph 196). Bittner et al teaches that intravenous administration of biotherapeutics is most typical in the clinic, but subcutaneous injections have been shown to be a safe, efficacious, and cost-effective dosing alternative valued by both patients and healthcare professionals because it can be administered at home (Abstract). Most approved antibodies are for intravenous or subcutaneous injections. Although some have been developed for intramuscular injections, new versions of the drug have been developed for subcutaneous injection (section Recent Advances in Subcutaneous Biotherapeutic Administration, pages 427-428). One skilled in the art would understand that when translating the mice experiments to human subjects, one would not use an intraperitoneal injection. One would be motivated to try other administration routes, selected from a list of finite number of administration routes more common and suitable for human subject. Intravenous injection and subcutaneous injection are identified and predictable potential solutions for administering biotherapeutics, especially antibodies, to human patients. Therefore, one of ordinary skill in the art would have had a reasonable expectation of success using these administration routes for treating human patients even without mouse trials with these administration routes. It is common for mouse trials with the antibody to use an administration route suitable for mouse without dictating the administration routes for humans.
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses that choosing from a finite number of identified, predictable solutions, with reasonable expectation of success, is obvious. Liang ‘429 teaches a finite list of administration routes for human patients and Bittner et al teaches the most common two for the delivering biotherapeutics, such as antibodies, to humans. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Instant claim 11 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-3, 15 of copending Application No. 17913429 (claims filed 03/23/2023) in view of Kato et al. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding instant claim 11, copending reference Liang ‘429 claims 1-3 and 15 teaches an anti-OX40 antibody and a method for treating cancer in a patient in need thereof, comprising of administering to the patient an effective dose of the anti-OX40 antibody or the fragment thereof.
Liang ‘429 does not explicitly teach the antibody could be used in a kit with instructions for administering the antibody to a patient in need thereof.
Kato et al teaches a kit including an anti-0X40 antibody, subsequence or fragment, and instructions for treating a subject in need of treatment with the OX40 antibody, subsequence or fragment (column 36, lines 38-43).
One of ordinary skill in the art would be motivated to substitute the anti-OX40 antibody taught by Liang ‘429 into the kit comprising of another anti-OX40 antibody taught by Kato et al.
One would be motivated to substitute the anti-OX40 antibody taught by Liang ‘429 into the kit taught by Kato et al because this antibody has shown anti-tumor effects and has therapeutic potential. Putting it inside a kit with instructions for its use in treating patients would be an obvious end goal for this antibody. One of ordinary skill in the art would have had a reasonable expectation of success because the kit taught by Kato et al is not specific to the specific anti-OX40 antibody taught by Kato et al, but would be routinely optimized for the particular anti-OX40 antibody that it comprises, as it emphasizes the need for suitable packaging, instructions for satisfactory clinical endpoints or adverse complications, buffering agents, preservatives, or a stabilizing agent (column 36, line 49 – column 37, line 13).
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses a simple substitution of one known element for another to obtain predictable results is obvious. Liang ‘429 teaches an anti-OX40 antibody with anti-tumor effects whereas Kato teaches that anti-OX40 antibodies that have therapeutic potential put into kits with instructions for their use in the treatment of patients in need thereof. It would be obvious to substitute the anti-OX40 antibody of Liang ‘429 into the kit taught by Kato et al. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Application No. 19166027
Instant claims 1-9 and 12-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 4-6, and 10-11 of copending Application No. 19166027 (claims filed 09/16/2025, hereafter referred to as Liang ‘027) in view of Liang ‘429. Although the claims at issue are not identical, they are not patentably distinct from each other. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding instant claim 1-9 and 12-20, copending reference Liang ‘027 claim 1 teaches the method of treating an inflammatory or immune disease comprising of administering the claimed anti-OX40 antibody or fragment. Liang ‘027 does not specifically claim cancers or tumors. Liang ‘429 teaches the disorders that can be treated by the same anti-OX40 antibody comprises cancers, relevant to instant claim 1-9 and 12-20, and all the cancers listed in instant claim 6 (paragraph 186).
Further regarding instant claim 1, copending reference Liang ‘027 claim 1 teaches a method for treating an inflammatory or immune disease comprising administering to a patient in need thereof an effective amount of an anti-OX40 antibody or an antigen-binding fragment, wherein the anti-OX40 antibody or antigen-binding fragment comprises the same six CDR sequences in instant claim 1. Instant SEQ ID NO: 1-6 have a 100% match to SEQ ID NO: 1-6 of Liang ‘027.
Further regarding instant claim 2, copending reference Liang ‘027 claim 4 teaches a method for treating an inflammatory or immune disease comprising administering to a patient in need thereof an effective amount of an anti-OX40 antibody or an antigen-binding fragment, wherein the anti-OX40 antibody or antigen-binding fragment comprises the same six VH and VL sequences as the instant claim. Instant SEQ ID NO: 7-8 have a 100% match to SEQ ID NO: 7-8 of Liang ‘027.
Further regarding instant claim 3, copending reference Liang ‘027 claim 5 teaches a method for treating an inflammatory or immune disease comprising administering to a patient in need thereof an effective amount of an anti-OX40 antibody or an antigen-binding fragment, wherein the anti-OX40 antibody or antigen-binding fragment comprises the same six VH and VL sequences as the instant claim. Instant SEQ ID NO: 9-10 have a 100% match to SEQ ID NO: 9-10 of Liang ‘027.
Further regarding instant claim 4-5, copending reference Liang ‘027 claim 6 teaches a method for treating an inflammatory or immune disease comprising administering to a patient in need thereof an effective amount of an anti-OX40 antibody or an antigen-binding fragment, wherein the anti-OX40 antibody or antigen-binding fragment has a fucosylation level of 0-10% or is expressed by a cell in which an a-(1,6)-fucosyltransferase gene is knocked out.
Further regarding instant claim 9, copending reference Liang ‘027 claim 11 teaches a method for treating an inflammatory or immune disease comprising administering to a patient in need thereof an effective amount of an anti-OX40 antibody or an antigen-binding fragment, wherein the dose of the anti-OX40 antibody or antigen-binding fragment is 0.01 mg/kg - 25 mg/kg, which exactly matches the values in instant claim 9.
It would have been prima facie obvious to one of ordinary skill in the art to apply the anti-OX40 antibody, taught by both Liang ‘027 and Liang ‘429, to cancers taught by Liang ‘429, to arrive at the method to treat cancers and tumors relevant to instant claims 1-9 and 12-20.
One of ordinary skill in the art would recognize the utility of the anti-OX40 antibody in methods for treating inflammatory or immune diseases, as taught by Liang ‘027, and be motivated to find other and specific disease indications for this anti-OX40 antibody. Especially since Liang ‘027 already taught the antibody is used in treating immune diseases, it would be obvious to look to treating cancers, which is a type of immune disease with a high motivation in the art to find antibodies for. One skilled in the art would have reasonable expectations of success because the exact same antibody already showed anti-tumor effects in Liang ‘429.
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses that known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art. The scope of the reference application and the art is in the same field of endeavor as the instant application and includes an analogous product, a method of treating an immune disease using an anti-OX40 antibody, to the instant application. Market incentives around discovering new cancer therapeutics would have prompted adaptation of an antibody used for treating inflammatory or immune disease, taught by Liang ‘027, towards treating cancer treatment, especially since it showed anti-tumor effects, as taught by Liang ‘429. This change in disease indication for one antibody is a common principle known in the art. One skilled in the art would have reasonable expectations of success because the exact same antibody already showed anti-tumor effects in Liang ‘429. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Further regarding instant claims 7 and 16-18, copending reference Liang ‘027 claim 10 teaches a dose range for the anti-OX40 antibody or fragment in the method. Further regarding instant claims 12-15 and 20, copending reference Liang ‘027 claim 11 teaches a dose range in mg/kg for the anti-OX40 antibody or fragment in the method. One of ordinary skill in the art would recognize that dose ranges are result-effective variables that a person of ordinary skill in the art would routinely optimize in methods of treatment using an antibody or antigen binding fragment. Differences in ranges of result-effective variables between the reference and instant application are not novel and are a matter of routine optimization. The principle of law states from MPEP §§ 2144.05: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages," (see In re Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382). Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation," (See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)).
Further regarding instant claims 8 and 19, copending reference Liang ‘027 claim 1 teaches the method of treatment using the antibody but does not explicitly state the administration frequency and treatment cycle. Liang ‘429 teaches potential administration timing for cancer treatment (page 16, paragraph 187). One of ordinary skill in the art would recognize that administration timing are result-effective variables that a person of ordinary skill in the art would routinely optimize in methods of treatment using an antibody or antigen binding fragment. Differences in ranges of result-effective variables between the reference and instant application are not novel and are a matter of routine optimization. The principle of law states from MPEP §§ 2144.05: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages," (see In re Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382). Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation," (See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)).
Instant claim 10 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 19166027 (claims filed 09/16/2025) in view of Liang ‘429 and further in view of Bittner et al. Although the claims at issue are not identical, they are not patentably distinct from each other. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The teachings of Liang ‘027 and Liang ‘429 as related to the method of instant claim 1, from which instant claim 10 depends are given previously in this Office Action and incorporated here. Liang ‘027 does not explicitly teach an administration route in the claims. Liang ‘429 teaches intraperitoneal administration of the anti-OX40 antibody into mice tumor models. Both do not explicitly teach in one embodiment intravenous injection and subcutaneous injection as administration routes, as in instant claim 10.
However, Liang ‘429 does teach that for pharmaceutical compositions for humans, examples of administration routes include intravenous, intradermal, subcutaneous, oral (e.g. inhalation), transdermal (i.e. topical), transmucosal, and rectal administration (paragraph 196). Bittner teaches that intravenous administration of biotherapeutics is most typical in the clinic, but subcutaneous injections have been shown to be a safe, efficacious, and cost-effective dosing alternative valued by both patients and healthcare professionals because it can be administered at home (Abstract). Most approved antibodies are for intravenous or subcutaneous injections. Although some have been developed for intramuscular injections, new versions of the drug have been developed for subcutaneous injection (section Recent Advances in Subcutaneous Biotherapeutic Administration, pages 427-428). One skilled in the art would understand that when translating the mice experiments to human subjects, one would not use an intraperitoneal injection. One would be motivated to try other administration routes, selected from a list of finite number of administration routes more common and suitable for human subject. Intravenous injection and subcutaneous injection are identified and predictable potential solutions for administering biotherapeutics, especially antibodies, to human patients. Therefore, one of ordinary skill in the art would have had a reasonable expectation of success using these administration routes for treating human patients even without mouse trials with these administration routes. It is common for mouse trials with the antibody to use an administration route suitable for mouse without dictating the administration routes for humans.
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses that choosing from a finite number of identified, predictable solutions, with reasonable expectation of success, is obvious. Liang ‘027 teaches the method of treating, Liang ‘429 teaches a finite list of administration routes for human patients, and Bittner teaches the most common two for the delivering biotherapeutics, such as antibodies, to humans. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Inventorship
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Conclusion
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/B.C./Examiner, Art Unit 1645 January 7, 2026
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674