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 .
Please note that the correspondence information for this application has changed (see Conclusion section at the end of this Action).
Claim Status
The amended claim set filed on 18 November 2022 is acknowledged. Claims 1, 4, 7, 10-11, 13-14, 16-18, 21-22, 27, 29, 31, 36, 39, 43, 55, 61, and 98 are currently pending. Of those, claims 1, 4, 7, 10-11, 13-14, 16, 18, 21, 22, 27, 29, 31, 36, 39, 43, 55, 61, and 98 are amended. There are no new claims and claims 61 and 98 are withdrawn. Claims 2-3, 5-6, 8-9, 12, 15, 17, 19-20, 23-26, 28, 30, 32-35, 37-38, 40-42, 44-54, 56-60, 62-97, and 99-115 are cancelled. Claims 1, 4, 7, 10-11, 13-14, 16-18, 21-22, 27, 29, 31, 36, 39, 43, and 55 will be examined on the merits herein.
Election/Restrictions
Applicant's election with traverse of Group I (claims 1, 4, 7, 10-11, 13-14, 16-18, 21-22, 27, 29, 31, 36, 39, 43, and 55) in the reply filed on 16 December 2025 is acknowledged. The traversal is on the ground(s) that MPEP 803 requires a showing of burden on the search and Applicant argues that search and examination of the entire application would not place a serious burden on the examiner. This is not found persuasive because the instant application is a 371 of a PCT application and, thus, is subject to unity of invention analysis for restrictions, which does not require a showing of search and examination burden. See MPEP 823. The requirement is still deemed proper and is therefore made FINAL.
Claims 61 and 98 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 16 December 2025.
Priority
The instant application is a 371 of application PCT/CN2021/094037 (filed 17 May 2021) and claims priority to foreign application CN 202010418720.5 (filed 18 May 2020). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. However, because no certified translation of the foreign priority document was provided, the foreign priority claim has not been perfected. Therefore, for the purposes of searching the prior art, the effective filing date of instant claims 1, 4, 7, 10-11, 13-14, 16-18, 21-22, 27, 29, 31, 36, 39, 43, and 55 is 17 May 2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 18 November 2022, 15 April 2024, 1 November 2024, and 14 July 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, each information disclosure statement is being considered by the examiner.
Claim Objections
Claim 11 is objected to because of the following informalities: in line 16, “APAMP” should read “APMAP”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 1, 4, 7, 10-11, 13-14, 16-18, 21-22, 27, 29, 31, 36, 39, 43, and 55 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.
The term “inner membrane” in claim 1is a relative term which renders the claim indefinite. The term “inner membrane” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Because the term “inner membrane” is not defined by the specification, it is unclear whether an inner membrane must be a membrane inside of an outer membrane, as in Gram-negative bacteria, or if an inner membrane is intended to refer to any membrane that is not the outer membrane of Gram-negative bacteria (i.e., encompassing the cytoplasmic membrane of Gram-positive bacteria). In the interest of compact prosecution, the term “inner membrane” is interpreted as referring to a membrane that is not the outer membrane of Gram-negative bacteria.
Regarding claim 4, where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The term “tumor cell” in claim 4 is referred to in the claim as an “organism,” while the accepted meaning is that a tumor cell is a cell within an organism and divides abnormally; thus, a tumor cell is not itself an organism. The term is indefinite because the specification does not clearly redefine the term.
The term “high affinity” in claim 11 is a relative term which renders the claim indefinite. The term “high affinity” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. As written, one of ordinary skill in the art cannot determine the scope of immunoglobulin epsilon receptor subunit γ that would be considered as having high affinity.
Regarding claim 16, where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The term “inner membrane” in claim 16 is recited as having any of the recited proteins, which includes intermembrane and outer membrane proteins, e.g., outer membrane protein TolC, an outer membrane usher protein FimD, an outer membrane porin OmpC, etc. However, one of ordinary skill in the art would not believe a bacterial inner membrane to comprise intermembrane or outer membrane proteins. The term is indefinite because the specification does not clearly redefine the term.
The term “inner core” in claim 18 is a relative term which renders the claim indefinite. The term “inner core” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. As written, one of ordinary skill in the art cannot determine the structural arrangement or relationship of the inner core relative to the membrane component and component derived from another organism. In the interest of compact prosecution, the scope of “inner core” is interpreted as encompassing anything in the pharmaceutical combination that is not located on the outer surface of the membrane component.
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.
Claim 39 is 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.
Claim 39 recites, “wherein the pharmaceutical combination comprises a particle and the particle comprises the inner core and the outer shell.” As written, claim 39 fails to further limit the scope of claim 29 because the particle does not necessarily comprise any element other than the inner core and the outer shell, which are both required in claim 29, thereby necessarily forming a “particle”. Claim 39 also does not limit the scope of claim 29 because it does not limit the structural arrangement of the outer shell and the inner core or provide any new features that limit the subject matter of claim 29.
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 § 102
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.
Claims 1, 4, 7, 10, 14, 16, 18, 21-22, and 55 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gunn et al. (WO 2017/185180 A1; cited in IDS; herein “Gunn”) as evidenced by Yoshizawa et al. (10 February 2020, Acta Cryst. F; herein “Yoshizawa”.
Regarding claim 1, 4, 7, 10, 14, and 16, Gunn teaches a combination comprising QBKPN, comprising inactivated Klebsiella pneumoniae cells, a Gram-positive bacterium (i.e., comprising a membrane component derived from an inner membrane of a bacterium) which comprises the protein FtsZ (as evidenced by Yoshizawa, Abstract), and gp100, a melanoma-associated antigen (i.e., a component derived from another organism than the bacterium) (para. 365-366).
Regarding claim 18, Gunn teaches that the combination may further comprise one or more adjuvants (para. 367), which is not part of the of the K. pneumoniae membrane component or gp100 antigen (para. 365-366). Gunn teaches that the composition can be formulated into liquid solutions or powders (para. 204). As written, claim 18 does not require any particular structural arrangement of the inner core and the membrane component and component derived from another organism; therefore, the scope of “inner core” encompasses anything in the pharmaceutical combination that is not located on the outer surface of the composition. However, the ingredients of the Gunn composition would be distributed throughout the liquid or powder, so the components would be both in the “inner core” and “outer surface” of the pharmaceutical composition/combination.
Regarding claim 21, Gunn teaches that the combination may comprise nanoparticles, including polylactide-coglycolide (PLGA) (para. 201).
Regarding claims 22 and 55, Gunn teaches that the combination comprises inactivated K. pneumoniae, which contains nucleic acids and that the combination may further comprise adjuvants (para. 367).
Claims 1, 4, 7, 10, 14, 18, 22, and 55 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Patel et al. (2019, Adv. Mater.; herein “Patel”).
Regarding claims 1, 4, 7, 10, and 14, Patel teaches multifunctional bacterial membrane coated nanoparticles (BNP) comprising the bacterial membrane from Mycobacterium smegmatis, which has only a cytoplasmic or inner membrane (paragraph bridging pages 1-2). The bacterial membrane is modified to comprise maleimide groups on its surface which bind antigens, thereby presenting the antigens from cancer cells to dendritic cells (pg. 1, right col., para. 3 and Figure 1). Once the antigens are bound to the maleimide groups, the BNP comprises the tumor antigens.
Regarding claim 18, Patel teaches that the BNP comprises an inner core (pg. 1, right col., para. 3).
Regarding claims 22 and 55, Patel teaches that the inner core comprises PC7A and CpG, which are immune adjuvants capable of further strengthening the antigen presentation in dendritic cells (pg. 2, left col.).
Claim Rejections - 35 USC § 103
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.
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 1, 4, 7, 10-11, 13-14, 18, 21-22, 27, 29, 31, 36, 39, 43, and 55 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (28 February 2020, Adv. Mater.; herein “Chen”) evidenced by Hegedüs et al. (2017, Front. Oncol.; herein “Hegedüs”) in view of Patel (2019, Adv. Mater.).
Regarding claims 1, 4, and 13, Chen teaches a eukaryotic-prokaryotic vesicle (EPV) nanoplatform comprising attenuated Salmonella outer membrane vesicles (OMV) and melanoma cytomembrane vesicles (i.e., cell membrane; CMV), i.e., a component derived from another organism (Abstract).
Regarding claims 7 and 10, Chen teaches that the EPV integrates immunogenic tumor antigens with natural adjuvants, and that the CMV component comprises membrane-bound melanoma-specific antigens Gp100 and TRP2 as well as other inherited membrane-bound proteins (pg. 2, right col., para. 2).
Regarding claim 11, Chen teaches that the CMV components come from the cell membrane (i.e., plasma membrane) of melanoma cells, which comprise the plasma membrane Ca2+ ATPase 4b encoded by ATP2B1-4 genes, as evidenced by Hegedüs (pg. 2, right col., para. 3).
Regarding claim 18 and 21, Chen teaches that the EPV comprises an inner core made up of PLGA and indocyanine green (ICG) (pg. 2, left col., para. 3 and Figure 1).
Regarding claim 27, Chen teaches that the diameter of the inner core is about 50 to 60 nm (pg. 2, right col., para. 3 and Figure 1G).
Regarding claims 29 and 39, Chen teaches that the EPV comprises both EPV and OMV components and forms an outer shell around the inner core, which together form the nanosphere (i.e., particle) of the EPV (pg. 2, left col., para. 2 and Figure 1A).
Regarding claim 31, Chen teaches that the EPV layer (i.e., outer shell) has a thickness of about 7 nm (pg. 2, right col., para. 3).
Regarding claim 36, Chen teaches that mass ratio of OMV (first membrane component) to CMV (second membrane component) is 1:2 (Figure 1D description).
Regarding claim 43, Chen teaches that the core-shell nanospheres (i.e., particle) have a diameter of 60-300 nm (pg. 2, right col., para. 3).
However, Chen does not teach a pharmaceutical combination comprising a first membrane component derived from an inner membrane of a bacterium, as in claim 1.
The teachings of Patel are set forth in para. 27-29 above, and teaches all limitations of claims 1, 4, 7, 10, 14, 18, 22, and 55.
Regarding claim 29, Patel teaches that the BNP comprises an outer layer (i.e., outer shell) comprising the bacterial membrane (pg. 1, right col., para. 3).
Regarding claim 39, Patel teaches that the BNP is a particle comprising an outer layer and an inner core (pg. 1, right col., para. 3 and Figure 1).
Therefore, it would have been prima facie obvious, before the effective filing date of the claimed invention, to a person of ordinary skill in the art, to modify the EPV of Chen by substituting the Salmonella OMV components with the Mycobacterium smegmatis membrane components taught by Patel and to combine the inner core taught by Chen with one or both of the inner core elements taught by Patel (i.e., adjuvants CpG and PC7A), thereby arriving at the invention of claims 1, 4, 7, 10, 13-14, 18, 21-21, 27, 29, 31, 36, 39, 43, and 55. The person of ordinary skill in the art would have been motivated to make the modification because the combination of melanoma membrane components presenting antigens and the modified M. smegmatis membrane components capable of taking up additional antigens released by cancer cells could allow for more cancer antigens to be presented to dendritic cells to elicit an immune response. Therefore, the combination is also desirable (see MPEP 2144(II)). The person of ordinary skill in the art would have had a reasonable expectation of success because Chen teaches the successful fusing of bacterial and cancer cell membranes to form a vesicle capable of stimulating an anticancer immune response (Abstract) and Patel teaches that the M. smegmatis membrane can also be used in vesicles for the same purpose. Therefore, the combination leads to expected results because each element performs the same function as is does individually.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that combining prior art elements according to known methods to yield predictable results, is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results. In the instant case, all elements (i.e., bacterial inner membrane component, tumor antigen, tumor membrane component, etc.) were known in the art. In addition, combining these elements yields a composition wherein each element merely performs the same function as it does separately; thus, the results of the combination would be recognized as predictable to one of ordinary skill in the art. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Regarding the range of inner core diameter recited in claim 27, Chen teaches an inner core diameter of 50-60 nm, which overlaps with the claimed range of about 60 nm to 100 nm. Regarding the range of outer shell thickness recited in claim 31, Chen teaches an outer shell thickness of about 7 nm, which is close to the claimed range of about 10 nm to about 20 nm. One of ordinary skill in the art would expect that the about 7 nm EPV would have similar properties to the claimed about 10 nm outer shell because the EPV of Chen comprises membrane components from two different organisms and form an outer shell combined with a core, as is taught by the claims. Regarding the range of particle diameter recited in claim 43, Chen teaches a EPV diameter range of 60-300 nm, encompasses the claimed range of about 70 nm to 120 nm. It is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985)) (see MPEP 2144.05.01). The courts have also found that “where 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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II. Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BAILEY M MORGAN whose telephone number is (703)756-5388. The examiner can normally be reached M-F 9-5 ET.
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/BAILEY M MORGAN/Examiner, Art Unit 1645
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642
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