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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on August 24, 2026 and Supplemental Response dated September 3, 2026, have been entered. By way of these submissions, Applicant has amended claims 1 and 52 and cancelled claims 36-37 and 44-46.
Claims 1, 7-8, 10, 14, 16, 20-22, 24, 27, and 51-55 are pending in the application. Claims 7-8, and 51 remain withdrawn from consideration, pursuant to the Restriction Requirement mailed June 27, 2022.
Claims 1, 10, 14, 16, 20-22, 24, 27, and 52-55 are therefore under examination before the Office.
The rejections of record can be found in the previous Office action, dated February 25, 2026.
Response to Amendment
Applicant argues that the cited references to Miller, Chan, Cooper, Terunuma, and Anjos do not teach every limitation of the claims as amended; specifically, the references do not teach that the NK cells are completely HLA mismatched. Applicant further argues that that the vaccine effect claimed is not inherent in the method of Miller, as the NK cells used in the instant claim are rejected by host lymphocytes within 4-15 days of administration, and this rejection is essential in creating the desired vaccine effect.
Applicant's amendments to the claims have addressed this issue, and the rejections under 35 U.S.C. 103 over Miller (Blood. 2005 Apr 15;105(8):3051-7), Chan (J Immunol. 2007 Jul 1;179(1):89-94), Cooper (Trends Immunol. 2001 Nov;22(11):633-40), Terunuma (US20160075996A1), Anjos (US20180169147A10), Tavel (J Interferon Cytokine Res. 2010 Jul;30(7):46 1-4), and O'Brien (J Acquir Immune Defic Syndr. 2013 July 1; 63(3): 280-288) are hereby withdrawn.
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 1, 10, 14, 16, 20-22, 24, 27, and 52-55 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. This is a new grounds of rejection.
The present claims are drawn to a method of treating a patient with HIV, a cancer, a viral infection, or a bacterial infection, comprising administering an effective amount of a lymphocytic cellular composition comprising activated natural killer (NK) cells and activated gamma delta T cells (GDT cells); wherein the NK cells are completely HLA-mismatched. However the instant specification, as filed, does not provide sufficient enabling description for treating the vast breadth of the diseases as encompassed by the claims because there does not appear to be sufficient in vitro or in vivo evidence to support administering the above composition to lessen the symptoms of all diseases within the scope of the claims.
The scope of diseases treatable by the claimed method is vast, encompassing dozens of different types of viruses, solid tumors, and bacteria (see pages 4-5 of the instant specification and claims 27, 51, and 53). These diseases include human immunodeficiency virus (HIV), viral hepatitis, Epstein-Barr virus, pancreatic cancer, breast cancer, lung cancers, ovarian cancer, prostate cancer, and infections of Clostridium, Staphylococcus, and Shigella, and many more.
For example, one of skill in the art is well-aware that cancer is difficult to treat. According to The Merck Manual of Diagnosis and Therapy, there are numerous molecular mechanisms which may drive cells to become cancerous, from genetic abnormalities to environmental factors. (The Merck Manuals Online Medical Library, [online]. Whitehouse Station, NJ: Merck Research Laboratories, 2006-2007. [retrieved on 10/19/2020]. Retrieved from the Internet: < URL: https://www.merckmanuals.com/professional/hematology-and-oncology/overview-of-cancer/cellular-and-molecular-basis-of-cancer >. Cellular and Molecular Basis of Cancer). However, the instant disclosure does not provide sufficient in vitro or in vivo evidence showing that the administration of the above composition can counter-act the cause or the manifestation of cancer as defined by The Merck Manual of Diagnosis and Therapy in order to treat all manifestations of the disease.
As further example, Applicant's specification lists pancreatic cancer as one possible type of cancer (page 5). Pancreatic cancer is highly lethal, and existing therapies only offer a modest benefit at best, as evidenced by Kotteas (Journal of Cancer Research & Clinical Oncology, 142.8: 1795-1805). Likewise, the varied tumor microenvironment in different types of cancer as well as the varied mechanisms of immune evasion of tumor cells makes immunological treatments unpredictable (see, e.g., Li-Lian, Cancers 12.7: 1872, entire document).
Pharmaceutical therapies in the absence of in vivo clinical data are unpredictable for the following reasons; (1) the protein may be inactivated before producing an effect, i.e. such as proteolytic degradation, immunological inactivation or due to an inherently short half-life of the protein; (2) the protein may not reach the target area because, i.e. the protein may not be able to cross the mucosa or the protein may be adsorbed by fluids, cells and tissues where the protein has no effect; and (3) other functional properties, known or unknown, may make the protein unsuitable for in vivo therapeutic use, i.e. such as adverse side effects prohibitive to the use of such treatment. See page 1338, footnote 7 of Ex parte Aggarwal, 23 USPQ2d 1334 (PTO Bd. Pat App. & Inter. 1992).
The specification only recites a single case study of a patient with HIV (Example 3A and Figure 2), claiming that the above method successfully reduced viral load to "nearly undetectable" levels (<20 HIV RNA copy/ml). Other examples are merely prophetic, stating proposed treatment methods without citing data from other diseases within the scope of the claims, most notably cancer.
Applicant has also repeatedly asserted that that use of HLA-mismatched NK cells produces a "vaccine" effect in the patient after the administered NK cells are eliminated by the patient's immune system within two weeks after administration, and that these properties are not present in the prior art, yet Applicant has cited no evidence that these properties are present as part of the claimed method.
The specification does not adequately teach how to effectively treat the breadth of diseases or reach an appropriate beneficial therapeutic endpoint in by administering the composition. The specification does not teach how to extrapolate data obtained from various in vitro or in vivo observations as well as clinical experience with the claimed composition to the development of effective methods of treating the plethora of the diseases broadly encompassed by the claimed invention.
There is insufficient guidance and direction as well as objective evidence provided for treating the scope of diseases encompassed by the claimed method. In view of the lack of predictability of the art (e.g., treating any cancer) to which the invention pertains, undue experimentation would be required to practice the claimed method of treating any cancer with a reasonable expectation of success, absent a specific and detailed description in Applicant's specification of how to effectively use the claimed composition and absent working examples providing evidence which is reasonably predictive that the claimed composition is effective for ameliorating any cancer, virus, or bacterial infection commensurate in scope with the claimed invention.
Reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view of the quantity of experimentation necessary, the limited working examples, the nature of the invention, the state of the prior art, the unpredictability of the art and the breadth of the claims, it would take undue trials and errors to practice the claimed invention.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER JOHANSEN whose telephone number is (571)272-0280. The examiner can normally be reached Monday-Friday, 6:00 to 2:00.
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/PETER JOHANSEN/Primary Examiner, Art Unit 1644
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