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 .
Restriction/Election of Species
Claims 20-23, 26, 28-29, 31, and 44-55 were pending.
Claims 20-23, 26, 28-29, 31, and 44-55 were subject to a restriction and election of species requirement by the previous Examiner in the Office Action mailed out on 29 December 2025.
In their Response filed on 02 March 2026, Applicant elected Group 1, claims 20-23, 26, 28-29, 31, and 44-45. Election was made with traverse, despite Applicant’s assertion otherwise (see Page 1 of Remarks, Paragraph 1), due to the presence of Arguments against the prior art used to break Unity of Invention by the previous Examiner.
In their Response filed on 02 March 2026, Applicant failed to elect any species as required by the Office Action mailed out on 29 December 2025. Even though the species election would not read on the elected group/invention and the corresponding claims, the election should still be made to be considered a proper response to the restriction and election of species requirement. The species election will be reiterated in this Office Action for the convenience of the Applicant.
The species are as follows:
Please elect one (1) tumor carrying EBV (Claims 50 and 55).
Please elect one (1) anti-tumor drug (Claim 52).
Regrettably, a typographical error was made in the previous Office Action with regard to the restriction. While there still are three groups, the three Groups should have been: Group I, claims 20-23, 26, and 28-29, drawn to a preparation method for a B cell composition; Group II, claims 31 and 44-48, drawn to a B cell vaccine prepared by the preparation method according to claim 20; and Group III, claims 49-55, drawn to a method of treating a patient having an Epstein-Barr virus-associated tumor comprising administering to the patient an anti-tumor drug comprising the B cell composition according to claim 31 or a method of treating a patient having a tumor carrying Epstein-Barr virus comprising administering to the patient the B cell vaccine according to claim 46. Examiner apologizes for the error in the previous Office Action.
Applicant elected Group I; however, the elected claims are Claims 20-23, 26, and 28-29.
The groups of inventions listed above do not related to a single general inventive concept of PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons:
The groups and multiples species of the generic invention lack unity of invention because, even though these groups require the technical feature of an EBV or EBV-antigen transformed allogenic B cell composition, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Yang and Wei (WO 2021/027057 A1, earliest Priority Date 18 October 2019).
Yang and Wei teach a B cell vaccine against a plurality of viruses and a preparation method thereof, wherein the vaccine is a composition comprising B cells and viral antigens wherein the composition has been subjected to a certain dose of ionizing radiation (see Abstract). Yang and Wei teach a preparation method for said B cell composition wherein said B cell is an allogenic B cell that is immortalized by infection with EBV, cultured and expanded, and then irradiated with ionizing radiation below the inactivation threshold (see Page 3, Paragraphs 2, 12; Page 4, Paragraphs 1, 8-13, 22).
For at least these reasons, the teachings of Yang and Wei at least render the claimed inventions of the instant application obvious and thus, even if shared technical features are present in the inventions encompassed by the instant claims, they do not represent a contribution over the prior art.
Response to Arguments
Applicant's arguments filed with respect to the breaking of Unity of Invention have been fully considered but they are not persuasive.
In their Response, Applicant argued that the combined teachings of Gu 2013 and Burns et al. 2015 did not render the instant claims obvious (see Page 1 of Remarks, Paragraph 2 – Page 4, Paragraph 1). Applicant also argued that the instant method of Claim 20 achieved unexpected technical effects over the prior art (see Page 4, Paragraph 2 – Page 5, Paragraph 2). As neither reference has been utilized in this new breaking of Unity of Invention, the Arguments presented against the previously used prior art are irrelevant. Thus, while the restriction requirement of the previous Office Action has not been made final, it is nonetheless maintained.
Applicant's arguments filed with respect to the other prior art documents cited by the previous Examiner have been acknowledged.
Applicant presented Arguments stating that the teachings of Hellebrand et al. (2006) and Steinman and Muenz (US 2006/0188520 A1, Published 24 August 2006) did not disclose or render obvious the invention encompassed by the instant claims. Examiner is merely putting on record that Applicant presented Arguments against the cited prior art and that said Arguments have been acknowledged. Since these prior art documents were not actually used to break unity or for a rejection of record, Examiner will not be responding to said arguments as no rebuttal is required.
Disposition of Claims
Applicant elected with traverse Group I, Claims 20-23, 26, and 28-29. Claims 31 and 44-55 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction and election requirement in the reply filed on 02 March 2026.
Accordingly, Claims 20-23, 26, and 28-29 will be examined on their merits.
Examiner’s Note
All paragraph numbers (¶) throughout this office action, unless otherwise noted, are from the US PGPub of this application US 2023/0405111 A1, Published 21 December 2023.
Applicant is encouraged to utilize the new web-based Automated Interview Request (AIR) tool for submitting interview requests; more information can be found at https://www.uspto.gov/patent/laws-and-regulations/interview-practice.
Priority
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in China on 24 July 2020. It is noted, however, that applicant has not filed an English translation of the certified copy of the CN202010728423.0 application as required by 37 CFR 1.55.
Should applicant desire to obtain the full benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e). While an English translation is not required unless an interference has been raised, it is suggested that one be filed of record to perfect the foreign priority effective filing date. Applicant is reminded that in the event that intervening art is found that falls between the foreign priority filing date and the 371-filing date, a prior art rejection may be raised since the certified copy of the foreign priority documents is not in English and an English translation of said documents has not been provided.
Failure to provide a certified translation may result in no benefit being accorded for the non-English application. Until a certified translation has been provided, the U.S. Effective Filing Date is set at 12 July 2021 for all claims under examination.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
The information disclosure statement filed 24 January 2023 fails to comply with 37 CFR 1.98(a)(3)(i) because it does not include a concise explanation of the relevance, as it is presently understood by the individual designated in 37 CFR 1.56(c) most knowledgeable about the content of the information, of each reference listed that is not in the English language. Specifically, Non-Patent Literature Documents #1, 2, and 4 (Bin Gu, 2013; Pingzhong Wang, 2003; and Written Opinion of International Searching Authority for International Application No. PCT/CN2021/105809, respectively) were not provided in English, no English translations have been provided, and no English Abstracts for Documents #1 and 2 have been provided. They have been placed in the application file, but the information referred to therein has not been considered.
The information disclosure statement (IDS) submitted on 24 January 2023 has been considered by the examiner. Any individual references with strikethroughs, however, have not been considered.
Specification
The spacing of the lines of the specification is such as to make reading difficult. New application papers with lines 1 1/2 or double spaced (see 37 CFR 1.52(b)(2)) on good quality paper are required.
The use of the term Provenge, 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.
The disclosure is objected to because of the following informalities: all instances of the phrase “ionizing irradiation” throughout the Specification (see Paragraphs 0008, 0010, at least) should be replaced with “ionizing radiation”.
Appropriate correction is required.
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claims 20-23, 26, and 28 are objected to because of the following informalities: in Claims 20, 26, and 28, all instances of the phrase “ionizing irradiation” should be replaced with “ionizing radiation”.
It is suggested that Claim 20 be amended to instead recite “A preparation method for a B cell composition, comprising the following steps: (1) collecting an allogeneic B cell that is diploid, wherein the allogeneic B cell is subject to immortalization treatment, and wherein the immortalization treatment involves infecting the allogeneic B cell with Epstein-Barr virus or an antigen of Epstein-Barr virus; (2) culturing and expanding the allogeneic B cell, wherein the allogeneic B cell carries an antigen of Epstein-Barr virus; and (3) irradiating the allogeneic B cells obtained in a dose of ionizing irradiation lower than inactivation threshold, wherein the ionizing irradiation is one or more of X-ray, γ ray, and Co60 isotope, wherein the dose of the ionizing irradiation is about 10-200Gy, wherein the dose rate of the ionizing irradiation is about 2-12Gy/min[[;]], and wherein the irradiation time is about 200-600s”.
In Claim 20, it is suggested that it say “…the immortalization treatment involves infecting the allogeneic B cell with Epstein-Barr virus or a virus encoding an antigen of Epstein-Barr virus” instead of “the immortalization treatment involves infecting the allogeneic B cell with Epstein-Barr virus or an antigen of Epstein-Barr virus”.
In Claim 21, it is suggested that it say “…wherein the culture conditions in step (2) are: 37°C, 5% CO2,…” instead of “…wherein culture condition of the step (2) is: 37°C, 5% CO2,…”.
In Claim 22, it is suggested that it say “…wherein the seeding density of the allogeneic B cell in
In Claim 23, it is suggested that it say “…wherein the number of generations of expansion…” instead of “…wherein number of generation of expansion…”.
In Claim 28, it is suggested that it say “…or 12Gy/min; and the irradiation time is…” instead of “…or 12Gy/min; the irradiation time is…”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b); Second Paragraph
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.
Claims 20, 26, and 28, and dependent claims 21-23 and 29 thereof, are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding Claims 20, 26, and 28, they all recite the term “about” in the context of the radiation dose, dose rate, and/or irradiation time. The use of the term “about” renders these claims indefinite, however, because it is unclear how much variation is encompassed by these claim limitations due to the lack of clear and specific definition in the instant Specification. Paragraph 0086 of the PGPub of the instant application attempts to define “about” by stating that “the term ‘about’…typically means +/- 5% of the stated value, +/- 4% of the stated value, more typically +/- 3% of the stated value, more typically, +/- 2% of the stated value, even more typically +/- 1% of the stated value, and even more typically +/- 0.5% of the stated value”. This definition is insufficient, however, as the use of the word “typically” introduces uncertainty and ambiguity because the definition cannot be applied in “atypical” situations. This means that in such situations “about” could encompass as much as 10%, 20%, or even 50% variation. It is suggested that the claims be amended by removing the term “about”, but Applicant is free to amend the claims as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claims 20, 26, and 28 are rejected on the grounds of being indefinite. Claims 21-23 and 29 are also rejected since they depend upon Claim 20 but do not remedy the deficiencies of Claim 20.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
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.
Claims 20-23, 26, and 28-29 are rejected under 35 U.S.C. 103 as being unpatentable over Demotte et al. (US 2010/0136597 A1, Published 03 June 2010), in view of West et al. (US 2002/0127634 A1, Published 12 September 2002), Sugimoto (U.S. Patent No. 4,621,052, Issued 04 November 1986), De Larichaudy (US 2018/0187150 A1, Published 05 July 2018), Gemeinhardt et al. (Gemeinhardt A, McDonald MP, König K, Aigner M, Mackensen A, Sandoghdar V. Label-Free Imaging of Single Proteins Secreted from Living Cells via iSCAT Microscopy. J Vis Exp. 2018 Nov 20;(141).), and Majumder and Boss (Majumder P, Boss JM. DNA methylation dysregulates and silences the HLA-DQ locus by altering chromatin architecture. Genes Immun. 2011 Jun;12(4):291-9.).
Demotte et al. teach a composition comprising irradiated, allogeneic EBV-immortalized B cells (see Paragraph 0019), wherein the irradiated, allogeneic EBV-immortalized B cells are cultured after being seeded at 1E6 cells (see Paragraph 0019).
Demotte et al. does not teach a preparation method for a B cell composition wherein the number of generations of expansion of the irradiated, allogeneic EBV-immortalized B cells is greater than 100 and cultured at 37°C and 5% CO2. Demotte et al. also does not teach wherein said B cells are obtained from a healthy person or the irradiation conditions and type of radiation used.
West et al. teach cell cultures comprising 1E6 irradiated EBV-transformed B cells, wherein the cells were irradiated at 8000 Rad (see Paragraph 0239), which is equivalent to 80Gy.
Sugimoto teaches human lymphoblastoid lines generated by transforming normal human lymphocytes by use of a suitable carcinogenic virus, such as EBV, agent or irradiation, such as X-ray irradiation (see Column 2, Lines 5-15).
De Larichaudy teaches culture compositions comprising non-proliferating B cells transformed by EBV, such as the LAZ388 cell line (see Paragraph 0064). De Larichaudy also teaches irradiation to block the proliferation of cells without detrimentally affecting their ability to express markers on the surfaces of the cells (see Paragraph 0090).
Gemeinhardt et al. teach that LAZ388 cells are cultured in RPMI 1640 medium supplemented with 10% fetal calf serum (FCS) and incubated at 37°C and 5% CO2 (see Page 9, Right Column, Paragraph 1).
Majumder and Boss teach that the LAZ388 cell line was originally derived from the peripheral blood of a patient with acute lymphocytic leukemia (see Cell culture subsection in Materials and Methods section) and that this cell line represented the normal B cells or lymphocytes of that patient (see Abstract) and was generated by transforming the cells with EBV (see Page 2, Last Paragraph).
A person having ordinary skill in the art would have been motivated to modify the teachings of Demotte et al. with those of West et al., Sugimoto, De Larichaudy, Gemeinhardt et al., and Majumder and Boss in order to develop a method for generating irradiated, allogeneic EBV-immortalized B cells. Demotte et al. and West et al. both teach the same starting number of cells to use, while West et al. also teach the dose of radiation. The teachings of De Larichaudy regarding irradiation to block the proliferation of cells without detrimentally affecting their ability to express markers on the surfaces of the cells reads on the instant limitation of “irradiation lower than inactivation threshold” of instant Claim 20. This means that the B cells will no longer grow but can still express antigens, for example, which can stimulate an immune response. Sugimoto teaches the transformation of normal human lymphocytes by use of a suitable carcinogenic virus, such as EBV, which reads on the instant limitation of the allogeneic B cell being obtained from a healthy person. These can obviously come from peripheral blood as discussed supra. The EBV-infected B cells will carry an EBV antigen. In addition, human B cells are diploid cells.
While none of the references explicitly describes the limitations of instant Claims 22-23, and 28, these claim limitations all recite results-effective variables, which are optimizable. As such, a skilled artisan would have known to find the optimal growth conditions, including number of passages necessary to generate a sufficient number of B cells and the seeding density depending on the desired final cell concentration, as well as the optimal irradiation conditions, including the dose rate and time. Routine optimization is not patentable. It has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980). Since Applicant has not disclosed that the specific limitations recited in instant claims are for any particular purpose or solve any stated problem, and the prior art teaches that parameter magnitudes that are encompassed by instant claims, often vary according to the sample being analyzed and various matrices, solutions and parameters appear to work equally as well, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the art. Thus, the combined teachings of these references render the instant claims obvious.
Such modifications, combining prior art elements according to known methods in order to yield predictable results, would have had a reasonable expectation of success and arrived at the claimed invention prior to the effective filing date of the instant application. For at least these reasons, instant Claims 20-23, 26, and 28-29 are rejected under 35 U.S.C. 103 as being unpatentable over the prior art.
Conclusion
No claims are allowed.
The prior art made of record, but not relied upon, and considered pertinent to applicant's disclosure is listed below:
Newell and Wade (US 2003/0138433, Published 24 July 2003)
Newell and Wade teach autologous adoptive immunotherapy with antigen-specific primed B cells to promote antigen-specific immune responses. This reference has not been utilized, as rejection would have been redundant to those set forth above.
Yang and Wei (WO 2021/027057 A1, earliest Priority Date 18 October 2019).
Yang and Wei teach a B cell vaccine against a plurality of viruses and a preparation method thereof, wherein the vaccine is a composition comprising B cells and viral antigens wherein the composition has been subjected to a certain dose of ionizing radiation. This reference has both Inventors in common with the instant application, but has a different Assignee. This reference has not been utilized, as rejection would have been redundant to those set forth above.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAREY A STUART whose telephone number is (703)756-4668. The examiner can normally be reached Monday - Friday, 7:30 AM - 4:30 PM EST.
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/CAREY ALEXANDER STUART/Examiner, Art Unit 1671 /Michael Allen/Supervisory Patent Examiner, Art Unit 1671
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