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 .
Election/Restrictions
Applicant's election with traverse of Group 3 (claims 2, 11, 12, 26, 40-45, 48-51) in the reply filed on 7/13/2026 is acknowledged. The traversal is on the ground(s) that Group 2 and 3 are drawn to a method of guiding antibody production in a non-animal for the production of select antibodies and that Groups 2 and 3 differs in that the immunogen used in one or more subsequent immunization differs from the immunogen used in the initial immunization and they request to examine Groups 2 and 3 together. This has been found persuasive and therefore, the restriction between Group 2 and 3 is withdrawn, and Groups 4 and 5 are now Groups 3 and 4, respectively. Thus, the elected Group 2 includes claims 2, 9, 11, 12, 14, 26, 40-45, and 48-51.
The requirement is still deemed proper and is therefore made FINAL.
Status of Application, Amendments, And/Or Claims
Claims 1-2, 9, 11-12, 14, 26,40-45, 48-51, 55, and 58-60 are pending.
Claims 1, 55, and 58-60 are withdrawn for being drawn to non-elected inventions (i.e., Groups I and III-IV).
Claims 2, 9, 11, 12, 14, 26, 40-45, and 48-51 are under examination.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) filed on 3/13/2024 and 3/5/2026 have been considered.
Priority
The instant application is a 371 of PCT/US2022/015279 filed on 2/4/2022.
Drawings
New corrected drawings in compliance with 37 CFR 1.121(d) are required in this application because FIG. 7B showing a graph and FIG. 7C legends are not legible. Applicant is advised to employ the services of a competent patent draftsperson outside the Office, as the U.S. Patent and Trademark Office no longer prepares new drawings. The corrected drawings are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112
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.
Claims 11-12 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 description in this case only sets forth method of guiding production in a non-human animal for the production of select antibodies, said method comprising: a. performing an initial immunization on a non-human animal with an immunogen; b. obtaining a blood sample comprising antibody secreting cells (ASCs) from said non- human animal; c. individually assaying ASCs present in the blood sample, or a fraction thereof, for the production of select antibodies; and d. performing a repeat cycle of steps when the percentage of ASCs producing select antibodies is below a threshold, wherein the cycle comprises: i. performing a subsequent immunization on the non-human animal with an immunogen, ii. Obtaining blood sample comprising ASCs from said non-human animal, and iii. Individually assaying ASCs present in the blood sample to produce select antibodies, and therefore the written description is not commensurate in scope with the claims which read on guiding production in a non-human animal for the production of select antibodies, said method comprising: a. performing an initial immunization on a non-human animal with an immunogen; b. obtaining a blood sample comprising antibody secreting cells (ASCs) from said non- human animal; c. individually assaying ASCs present in the blood sample, or a fraction thereof, for the production of select antibodies; and d. performing a repeat cycle of steps a.-c. if the threshold is lower than a target level, wherein the immunogen of the subsequent immunization is different from the immunogen of the initial immunization.
Jin et al. teach immunizing with an antigen to a subject and screening for antigen specific antibody-secreting cells (ASCs) in humans (see abstract). They teach that the method does not have to limit for a human and therefore, they teach a unique method for detecting individual ASCs using microwell array chips, which enables the analysis of living cells and offers a rapid, efficient and high throughput (up to 234,000 individual cells). Reddy et al. teaches making monoclonal antibodies and isolating them from animals (see Title, abstract). They teach that the analysis of the antibody secreting cell population in the mouse indicates that serum may contain as many as 500 different antibodies of which multiple may be of same antigen specificity (0073). They teach that ASC are terminally or near terminally differentiated B cells (including plasma cells and plasmablasts) (00120). They teach that antigen secreting B cells are CD138+ plasma cells and plasmablasts) [00257]. Neither the prior art nor the specification discloses the reason for administering a different immunogen which is different from the initial immunogen used for generating antibody. There is no nexus of claim 2 and the requirement for a different antigen from the initial antigen.
Therefore, only a method of guiding production in a non-human animal for the production of select antibodies, said method comprising: a. performing an initial immunization on a non-human animal with an immunogen; b. obtaining a blood sample comprising antibody secreting cells (ASCs) from said non- human animal; c. individually assaying ASCs present in the blood sample, or a fraction thereof, for the production of select antibodies; and d. performing a repeat cycle of steps when the percentage of ASCs producing select antibodies is below a threshold, wherein the cycle comprises: i. performing a subsequent immunization on the non-human animal with an immunogen, ii. Obtaining blood sample comprising ASCs from said non-human animal, and iii. Individually assaying ASCs present in the blood sample to produce select antibodies, but not the full breadth of the claim meets the written description provision of 35 U.S.C. §112, first paragraph.
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. 112 is severable from its enablement provision (see page 1115).
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.
Claim(s) 2, 9, 11, 12, 14, 26, 40-45, and 48-51 are rejected under 35 U.S.C. 103 as being unpatentable over Jin et al. (IDS, Nature Med. 2009, 15: 1088-1093) in view of Lee et al. (IDS, WO 2009/035738), and Reddy et al. (WO 2011146514)
The instant claims are broadly drawn to a method of guiding antibody production in a non-human animal for the production of select antibodies, said method comprising: a. performing an initial immunization on a non-human animal with an immunogen; b. obtaining a blood sample comprising antibody secreting cells (ASCs) from said non- human animal; c. individually assaying ASCs present in the blood sample, or a fraction thereof, for the production of select antibodies; and d. performing a repeat cycle of steps when the percentage of ASCs producing select antibodies is below a threshold, wherein the cycle comprises: i. performing a subsequent immunization on the non-human animal with an immunogen, ii. Obtaining blood sample comprising ASCs from said non-human animal, and iii. Individually assaying ASCs present in the blood sample to produce select antibodies (claim 2, 9), the method of claim 9, and step e. isolating the select antibodies and/or ASC producing the select antibodies (claim 14), wherein the antibodies bind to any or all of (i)-(v) (claim 26), wherein the blood sample is obtained from the non-human animal about 3 to about 7 days after the immunizing step (claim 40), wherein the blood sample obtained from the non- human animal is less than or about 500 µL (claim 41-42), wherein the ASCs are CD138+ B cells (claim 43), wherein the ASCs comprise migratory plasmablasts (claim 44), further comprising removing one or more components of the blood sample obtained from the non-human animal prior to assaying (claim 45).The method of claim 2, wherein the non-human animal is subjected to neither removal of one or more secondary lymphoid organs nor euthanasia (claim 48), wherein ASCs from blood sample are not used in making hybridomas (claim 49, does not carry a patentable weight). The method of claim 2, wherein the non-human animal is one of a series of non-human animals, and an outcome of the assaying is the identification of the non-human animals having a number of ASCs producing select antibodies below the threshold and/or requiring further immunization (claim 50). The method of claim 2, wherein the steps of the method are carried out on a series of non-human animals and the method comprises profiling the B-cell repertoire of the blood sample for each non-human animal of the series and selecting a subset of the series having a target B-cell profile (claim 51).
Jin et al. teach immunizing with an antigen to a subject and screening for antigen specific antibody-secreting cells (ASCs) in humans (see abstract). They teach that the method does not have to limit for a human and therefore, they teach a unique method for detecting individual ASCs using microwell array chips, which enables the analysis of living cells or a single cell basis and offers a rapid, efficient and high throughput (up to 234,000 individual cells). They teach that the method has successfully been used to detect and retrieve ASCs for hepatitis B virus (see Table 1) and influenza viruses. They teach that the system is useful for detecting multiple antigens as well as for the selection of ASCs secreting high-affinity antibodies on a chip. They teach that assay can be done in a 50 Um or 100 um diameter, and depth well (page 1092). They use ELISPOT to detect the expression of antibodies. They do not teach that assay needs to be done in a non-human animal. However, the method is suitable for a human subject as well as a non-human subject, contrary to evidence.
Lee et al. also teaches a method of administering a booster immunization in a subject, comprising obtaining peripheral blood mononuclear cells (PBMC) from the subject between 5-15 days and measuring the number of antibody secreting cells in the PBMC and suggests that if ASCs in the PBMC are lower to standard, then to do repeat immunization (pg. lines 25+). Therefore, (regarding claims 48) there is no need to remove one or more secondary lymphoid cells.
Reddy et al. teaches making monoclonal antibodies and isolating them from animals (see Title, abstract). They teach that the analysis of the antibody secreting cell population in the mouse indicates that serum may contain as many as 500 different antibodies of which multiple may be of same antigen specificity (0074). They teach that ASC are terminally or near terminally differentiated B cells (including plasma cells and plasmablasts) (00120). They teach that antigen secreting B cells are CD138+ plasma cells and plasmablasts) [00257].
Therefore, it would have been prima facie obvious to one ordinary skill in the art at the time the invention was made to determine ASCs having CD138+ B cells in a non-human animal (mouse) as taught by Reddy et al and perform a repeat immunogen if the titer level is lower than a target level as taught by Lee et al to immunize a non-human animal using one and more antigens as taught by Jin et al. Additionally, one would have been motivated to do so because Lee et al teach repeat action of immunization to achieve above threshold titer of an antibody by measuring in ASCs and Reddy et al teach generating antibodies in non-human animal where ASCs comprising CD138+ B cells. Further, one would have a reasonable expectation of success in generating antibodies fast by repeat immunization as taught by Lee et al by one or more antigens as taught by Jin et al by determining the level of ASCs in blood samples collected from immunized animal wherein the ASC comprises CD138+ B cells as taught by Reddy et al. Therefore, the instantly claimed invention as whole would have been obvious over the combined teachings of prior art.
Expected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof." See In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1967) (resultant decrease of dental enamel solubility accomplished by adding an acidic buffering agent to a fluoride containing dentifrice was expected based on the teaching of the prior art); Ex parte Blanc, 13 USPQ2d 1383 (Bd. Pat. App. & Inter. 1989); see also MPEP §716.02(c). Additionally, “[it] is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) and MPEP § 2144.06.
Conclusion
No claim is allowed.
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/GYAN CHANDRA/Primary Examiner, Art Unit 1674
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