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 .
Claim Status
Claims 1-10 are pending.
Claims 1-10 have been examined.
Claims 1-10 are rejected.
Priority
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in China on 13-Dec-2023. It is noted, however, that applicant has not filed a certified copy of the CN202311711394.7 application as required by 37 CFR 1.55.
Specification
The disclosure is objected to because of the following informalities:
Paragraph 15 recites that the IR780 and PLGA is dissolved in dichloromethane, but paragraph 50 later recites chloroform (CHCl3) as the diluent.
Paragraph 42 recites Embodiment 11, but implementation examples are only from 1-10 (Paragraphs 61-99).
Figure 8 of paragraph 32 recites the figure as Embodiment 5, and Figure 9 as Embodiment 6 (Paragraphs 31 and 32, respectively). However, the implementation example references Figure 8 for Embodiment 4, and Figure 9 for Embodiment 5.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 9 and 10 are 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 9 and 10 depends on claims 3 and 8, respectively, but only add structural characterization that define IR780, WRG-28, and PLGA that do not further limit claims 3 and 8. 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 § 103
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claim(s) 1-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (WO2013052167A2, Published 11-Apr-2013), and further in view of Pei et al. (Published 14-Dec-2020) and Grither et al. (Published 30-Jul-2018).
In regards to Claims 1 and 2, Zhang teaches a PLGA core loaded with an immunological adjuvant and then coated with a cancer cell membrane to treat breast cancer (Example 3, Paragraph 192 and 193). Zhang further teaches the motivation for coating the PLGA core is due to the limitation of individual tumor associate antigens (TAAs), and the strategy of translocating the entire cell membrane onto the nanoparticle, all of the surface membrane TAAs are in their native environment, and can therefore faithfully present antigen presenting cells in their native form (Example 3, Paragraph 190).
In regards to Claim 3-7, and 9, Zhang teaches a method where the patient’s cancer cells or common cancer cell line cells are homogenized and the homogenate is then spun down, with the supernatant with membrane is collected. PLGA nanoparticles are then created by dissolving PLGA and an adjuvant into an organic phase, precipitated using an aqueous phase to form nanoparticles. The PLGA nanoparticles are then coated with the cancer cell membrane to form the final particles (Page 69-70).
In regards to Claims 8 and 10, Zhang teaches performing in vitro and in vivo experiments to evaluate the efficacy of the cancer cell membrane coated PLGA nanoparticles including antigen studies, T-cell-activation, and therapeutic efficacy studies in a murine tumor model (Paragraph 194).
However, Zhang does not teach EO771 breast cancer cell membrane, IR780 and the DDR2 inhibitor of WRG-28 of claims 1 and 2. Zhang does not teach loading IR780 and WRG-28 into PLGA nanoparticles, use of a cell extraction kit, phenylmethylsulfonyl fluoride, freeze-thaw processing, purification procedure, or coating nanoparticles with an EO771 breast cancer cell membrane of claims 3-7, and 9. Zhang does not teach all of the recited functional testing of the biomimetic nanosphere such as photothermal evaluation and DDR2 inhibition of claim 8 and 10. For this reason, Pei and Grither are added.
Pei teaches the incorporation of IR780 into PLGA nanoparticles for photothermal therapy in breast cancers. Pei specifically teaches dissolving IR780 and PLGA into dichloromethane, forming PLGA nanoparticles through ultrasonic emulsification with PVA, washing the resultant nanoparticles, and coating the nanoparticles with a biological membrane (Page 10153) to improve tumor targeting, longevity, and therapeutic efficacy(Page 10155). Pei further teaches that the IR780 functions as a near infrared photothermal agent that generates heat upon laser irradiation to induce tumor cell death, further characterized by the evaluation temperature change (Page 10158, Fig 3B) and tumor effect (Page 10160, Fig 5B).
Grither teaches that DDR2 signaling within cancer-associated fibroblasts (CAFs) promotes tumor progression, collagen remodeling, invasion, and metastasis in breast cancers (Page 7786).
WRG-28 as an allosteric inhibitor that inhibits, remodels the tumor stromal extracellular matrix leading to proinvasive collagen organization (Page 7786), and the interaction of DDR2 in breast tumor cells and tumor stromal CAFs is critical to blunting metastasis, migration, and promotes SNAIL1 protein stabilization (Page 7789-7790).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the cancer cell membrane coated PLGA nanoparticle platform of Zhang by loading the PLGA nanoparticles with IR780 of Pei and WRG-28 of Grither. One would have been motivated to do so because Zhang teaches a versatile PLGA based, membrane coated drug delivery system designed to encapsulate therapeutic agents while providing specific tumor targeting. Pei teaches that IR780 provides photothermal tumor killing while delivered in a PLGA nanoparticle package, while Grither teaches that inhibition of DDR2 by WRG-28 suppresses CAF mediated stromal remodeling and metastasis in breast cancers. A person having ordinary skill in the art would have reasonably expected that co-delivery of IR780 and WRG-28 within Zhang’s nanoparticle platform would have provided the combined benefits of targeted delivery, tumor ablation, tumor inhibition, metastasis inhibition with reasonable expectation of success.
Further, Zhang teaches coating nanoparticles with membranes derived from cancer cells, including breast cancer cells, to achieve homologous targeting. EO771 represent a known breast cancer cell line suitable for generating breast cancer derived membrane coatings, and the selection of one known breast cancer cell line over another would have constituted an obvious design choice yielding predictable results. The selection of an EO771 breast cancer cell membrane would have been an obvious choice among breast cancer cell sources since EO771 is a known breast cancer cell line and would have expected predictable results as the membrane coating functionality taught by Zhang.
Zhuang and Pei collectively teach preparations of drug loaded PLGA nanoparticles, isolation of cellular membranes, and coating of nanoparticles with membranes. The use of a membrane extraction kit, PMSF reagent, freeze-thaw cycles, purification procedures, centrifugation conditions, PBS washing, and related membrane isolation techniques represent routine laboratory procedures. Further, the specific process parameters recited including concentration, PLGA characteristics, cell counts, reagent quantity, sonication and stirring times, and washing steps represent result-effective variables affecting nanoparticle formation, yield, and encapsulation efficiency that would have been optimized through routine experimentation to obtain predictable results.
Furthermore, Zhang, Pei, and Grither collective evaluate antitumor activity, immune response, photothermal activity, tumor targeting, and metastatic behavior. Therefore, it would have been obvious to perform the recited functional testing as a matter of routine characterization and efficacy assessment of the modified membrane coated nanoparticle drug delivery system. For the forgoing reasons, Claims 1-10 are rendered obvious by the teachings of the prior art.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WENHAN LI whose telephone number is (571)272-9143. The examiner can normally be reached Monday-Friday 7:30 am-5 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached at (571)272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/W.L./Examiner, Art Unit 1614
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614
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