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 .
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.
Election/Restrictions
Applicant's election with traverse of Group I and the species of equal amounts in the reply filed on 7/31/26 is acknowledged.
The traversal is on the ground(s) that examining the methods with the composition would not pose an undue burden since the elected composition is a requirement of the method claims. This is not found persuasive because the instant application is a 371 and so is restricted under unity of invention. The argument that there is no search burden is not an argument that the inventions share unity and so is not persuasive. Further, even to the extent that search burden might be considered, a method requires search and consideration beyond the composition in isolation and so the mere fact that the method requires the composition is inadequate to establish that there would be no undue search burden.
The requirement is still deemed proper and is therefore made FINAL.
Applicant did not elect one of the diseases recited in claim 41 as required (Restriction mailed 6/4/26 p.3). As this election is not necessary for the examination of Group I, an Office action is issued herein. Note, however, that compliance with a Restriction requirement requires an election even if the election is traversed. In Applicant’s response to this Office Action, election of the necessary species of disease is required.
Claims 1-51 are pending.
Claims 17-51 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 7/31/26.
Claim 11 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 7/31/26.
Claims 1-10 and 12-16 are under examination.
Drawings
The drawings are objected to because:
Figure 2: the symbols in the legend are illegible. The lines in the graph are indistinguishable from one another in certain cases and none can be attributed to the legend ID because of the illegibility of said legend and the similarity in grey tones of the graph.
Figure 3: none of the text is legible in either the legend or the graph itself, e.g., the axes labels.
Figure 5: the X-axis labels are illegible.
Figure 8: the symbols for the legend appear identical, e.g., the shading for “baseline” is indistinguishable from “C3D14”, which is indistinguishable from 1 year, etc.
Figure 9: the same symbols appear to be used more than once. For example, ID 1 appears the same as ID3, ID5, and ID 7. This makes the graph itself uninterpretable because it is unclear which line is which.
Figure 14: the text is illegible throughout the figure.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112
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.
Claim 8 is 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 claim states the GM-CSF is “derived from” human. The specification does not provide an explicit definition. At page 16, the specification notes that “derived from” can mean “native to”, i.e., how or where the GM-CSF exists in nature. This raises the question of what else “derived from” could mean. The phrase might be limited to human GM-CSF sequences whether they are naturally or synthetically obtained. The phrase might include mutations in known human GM-CSF sequences so long as the protein maintains some undisclosed similarity to the native sequence. The phrase might include changing each and every residue of a human GM-CSF sequence so long as the starting material was human. The specification does not fairly warn others as to the scope of “derived from” and so the claim is indefinite.
Therefore, claim 8 is indefinite.
Claim 15 is 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.
Claim 1 is a composition of matter. Claim 12 describes a result “when administered”. This is considered to be describing an inherent property of the composition rather than a required result of an administration step. Claims 13 and 14 are also describing desired results/properties of the composition without requiring any active step nor requiring these results are actually achieved. By their dependence on claim 12, it is clear that the “when administered” is still part of these claims as a description of properties rather than a step.
However, claim 15 recites “is determined”. Rather than a property or desired result, the phrase “is determined” suggests a requirement of an active determination step. Adding process steps to a product claim is indefinite as it creates confusion as to when direct infringement occurs; MPEP §2173.05(p)(II). It is unclear if claim 15 is still describing a property (causing remission is a potential outcome which could be determined as a non-detectable spike) or if claim 15 is now requiring such a determination step—in which case the claim is additionally indefinite for adding method steps to a composition claim.
Therefore, claim 15 is indefinite.
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.
Claim 1-3, 9, 10, and 12-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for K562 cells that express GM-CSF at sufficient levels, does not reasonably provide enablement for the breadth of all K562 cells. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
There are many factors considered when determining if the disclosure satisfies the enablement requirement and whether any necessary experimentation is undue. These factors include, but are not limited to: 1) nature of the invention, 2) breadth of claims, 3) amount of direction or guidance by the inventor, 4) relative skill of those in the art, 5) level of predictability in the art, 6) state of the prior art, 7) existence of working examples, and 8) quantity of the experimentation needed to make or use the invention. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)
When a compound is limited by a particular use, enablement of the claim is evaluated based on that limitation (MPEP §2164.01(c)). Currently, claim 1 recites an intended use: for use in raising an immune response to a plasma cell disorder in a subject. It is this use that the composition is evaluated for.
Claim 2, which depends from claim 1, recites the composition is a vaccine. Under §112d, a dependent claim must be further limiting. This would then require that the composition of claim 1 includes such compositions that are not vaccines, yet the specification defines a “vaccine” at p.11: a product or composition that stimulates a subject’s immune system to produce immunity to a specific disease or condition, thus protecting the subject from that disease. Raising an immune response (stimulates a subject’s immune system) is part of this definition. While the definition of “vaccine” requires the production of immunity, the specification as filed does not appear to provide any utility for raising an immune response other than to act as a vaccine.
The specification does not adequately describe uses for the composition comprising three cell types for uses other than as a vaccine, such as raising an immune response with no other effect. In particular, the guidance in the specification appears limited to K562 cells expressing GM-CSF. There does not appear to be a disclosure of K562 cells which do not express this protein nor of a reasonable use for such cells. The claims therefore require others to determine 1) if K562 cells lacking GM-CSF function as a vaccine/raise an immune response, 2) if K562 cells expressing some other protein will act as a vaccine/raise an immune response, and 3) what other uses naturally occurring U266, H929, and K562 cells might have. The art (see below) recognizes this composition as a vaccine as well but does not provide sufficient guidance on other such uses or for non-GM-CSF expressing K562 cells to rectify this deficiency. Determining a reasonable use commensurate with the broad scope of what is claimed and for determining the breadth of non-GM-CSF expressing K562 cells to act as a vaccine would require undue experimentation.
Therefore, claims 1-3, 9, 10, and 12-16 are not enabled for their full scope.
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 2 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 1 requires a composition with certain cells. Claim 2 adds the potential limitation of this same composition “is a vaccine”. The specification defines a “vaccine” at p.11: a product or composition that stimulates a subject’s immune system to produce immunity to a specific disease or condition, thus protecting the subject from that disease. This is a definition directed wholly to the properties of the composition and does not require any particular structure. Further, the specification discloses the composition as performing this function (see enablement rejection above). Considering the claims and the specification as a whole, claim 2 appears to describe a property of claim 1 but does not add any further limitation.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-8, 10, and 12-16 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Biavati (IDS 6/13/25 NPL citation 3) as evidenced by Biavati 2021 (IDS 6/13/25 NPL citation 6) and Smith (IDS 12/26/23 NPL citation 2).
Regarding claim 1, Biavati teaches a vaccine comprising U266 and H292 cell lines plus a GM-CSF producing leukemia cell line K562 (p.1 last paragraph). This meets the limitations of a composition comprising U266, H929, and K562 cells. With respect to the preamble, the “for use” is an intended use, does not offer any structural requirements for the composition, and so does not alter the scope of the claim (MPEP §2111.02(II)). Nevertheless, Biavati teaches the composition is a vaccine and so the evidence supports the conclusion that the Biavati composition could be used as such; see also the Results section of Biavati.
Regarding claim 2, the phrase “is a vaccine” appears directed at a function of the composition rather than any required structural element (see above). Nevertheless, Biavati also teaches the composition is a vaccine (p.1 last paragraph) and that the vaccine induces an anti-tumor immune response (p.2 last paragraph).
Regarding claim 3, the phrase “is allogenic” appears directed at a function of the composition rather than any required structural element. A composition meeting all of the structural requirements of the claim must necessarily possess the same functions/properties. Chemical compounds and their properties are inseparable (In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA1963)), as are their processes and yields (In re Von Schickh, 362 F.2d 821, 150 USPQ 300 (CCPA 1966)). Further, Biavati teaches the vaccine is allogenic (p.2 last paragraph).
Regarding claim 4, Biavati teaches the K562 cells are a GM-CSF producing leukemia cell line K562 (p.1 last paragraph), thereby teaching the K562 cells express (produce) GM-CSF.
Regarding claim 5, this is a product-by-process claim describing how (the process) the GM-CSF was introduced into the K562 cell such that the protein is expressed (product). There does not appear to be any clear structural difference between a K562 cell expressing GM-CSF because the cell was transfected compared to a K562 cell expressing GM-CSF because of some other manipulation achieving the same result. A composition is analyzed on the structure of the composition, not the manner by which it was made. As the GM-CSF expressing cells of Biavati appear substantially identical to one which was transfected, burden is shifted to Applicant to show a non-obvious difference (MPEP §2113).
Regarding claims 6-7, these are properties of the cells themselves and the Office is not equipped to obtain and test prior art products and make comparisons thereof (In re Brown, 459 F.2d 531, 535, 173 USPQ 685, 688 (CCPA 1972)). As Biavati meets all of the structural requirements of the instant claims and so the properties thereof must also be present; chemical compounds and their properties are inseparable (In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA1963)), as are their processes and yields (In re Von Schickh, 362 F.2d 821, 150 USPQ 300 (CCPA 1966)).
Regarding claim 8, Biavati teaches the cells express GM-CSF but does not explicitly state that it is human derived. The source of the GM-CSF is an inherent property of the composition of Biavati and, in once case, Biavati used human GM-CSF. Further, given the indefiniteness of “human derived” discussed above, any GM-CSF could be considered “human derived”. As a composition is determined based on the structure rather than its source, the evidence supports the conclusion that the GM-CSF of Biavati is patentably indistinct from a “human derived” GM-CSF.
Regarding claim 10, Biavati teaches the U266 and H929 cells are in the composition but does not state at what amounts. A generic disclosure will anticipate a claimed species when the species can be at once envisaged from the disclosure (MPEP §2131.02). Comparing the genus of the prior art to the claimed species, there are two species within the genus: equal amounts and unequal amounts (instant claims 10 and 11). One could have immediately envisaged these two options and so Biavati anticipates this species.
Regarding claims 12-14, these are properties of the composition. Chemical compounds and their properties are inseparable (In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA1963)), as are their processes and yields (In re Von Schickh, 362 F.2d 821, 150 USPQ 300 (CCPA 1966)). Since the composition of Biavati meets all of the claimed structural limitations of the claims, the properties must also be necessarily present.
Regarding claim 15, in one interpretation, this claim also sets forth properties of the composition and so is also inherent.
Further regarding claims 12-15, Biavati teaches the composition for inducing a “complete response” (complete remission), that complete remission is measured by an absent M-spike with positive immunofixation, improved (prolonged) progression free survival, and that the composition induces an immune response that protects the subject (vaccine). This further supports the conclusion that these properties are present in the Biavati composition.
Regarding claim 16, the subject being human is modifying limitations solely in the preamble and are directed to an intended use. For the reasons above, the subject being human does not alter the scope of the claims directed to a composition, e.g., the subject being human does not alter the structure of the composition itself. Further, Biavati administers the composition to patients (human subjects; p.2) and so the composition is clearly capable of being administered to human subjects.
Finally, regarding claims directed to properties of the cells (e.g., claims 5-8), Biavati teaches the K562 cells are GVAX® (p.1). The Biavati 2021 document (IDS 6/13/25 NPL citation 6) appears to disclose the same U266+H929+GM-CSF secreting K562 cells as GVAX® (MM-GVAX; p.6697 C2). Biavati 2021 is explicit that the U266 and H929 cells are in equal numbers (50 million each), further supporting the conclusion that the composition in Biavati are also in equal numbers. Smith teaches K562 cells expressing GM-CSF called GVAX® (p.2; reference list 4). Smith teaches this is allogenic, a vaccine, was transfected with human GM-CSF, and produces 1000 ng/1x106 cells. This serves as further evidence that the composition of Biavati possesses the claimed properties.
Therefore, claims 1-8, 10, and 12-16 are anticipated by Biavati.
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.
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.
Claim(s) 5-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Biavati as applied to claims 1-4 and 12-16 above, and further in view of Smith (IDS 12/26/23 NPL citation 2).
The discussion of Biavati as it applies to the claims is above and incorporated herein. While the properties of the cells in claims 5-8 are considered inherent properties of the Biavati composition, in the alternative, these would have been obvious in view of Smith. Smith is also concerned with GM-CSF K562 cells called GVAX® that serves as a vaccine in the same way as Biavati. Smith teaches these K562 cells expressing GM-CSF is allogenic, a vaccine, was transfected with human GM-CSF, and produces 1000 ng/1x106 cells. It would have been obvious to one of ordinary skill in the art at the time of filing to use the K562 cells of Smith in the composition of Biavati. Biavati teaches the composition should comprise K562 cells that express GM-CSF to act as a vaccine and Smith teaches such cells that were demonstrated to act as a vaccine.
With respect to claims 9 and 10, the components of the composition are found in the prior art. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here 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). “[I]t is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions” (MPEP §2144.05(II)(A)).
For these reasons, arriving at “equal amounts” and a ratio of 20:1 are considered not to support the patentability of the claims. The components are taught by the prior art and these claims are directed solely to the proportions of those components. The prior art teaches the same intended effect (use in raising an immune response, vaccine, etc.) and so these changes in proportion—if such exist—are deemed obvious.
Therefore, claims 1-10 and 12-16 would have been obvious.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Biavati 2020 (IDS 6/13/25 NPL 4) is a similar disclosure to Biavati used in the rejections above. Biavati 2020 also references NCT01349569.
ClinicalTrials (form 892) describes trial NCT01349569 and was available 1/15/2019. The disclosure is similar to the above art, teaching e.g., allogenic vaccines comprising GM-CSF K562 cells. This document does not explicitly state the vaccine comprises U266 and H929 cells, but the description of these elements in Biavati 2020 indicate these were necessarily present.
Noonan (form 892) also teaches an allogenic vaccine comprising U266, H929, and GM-CSF K562 cells.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ADAM M WEIDNER whose telephone number is (571)272-3045. The examiner can normally be reached M-T 9-18; W-R 9-15.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Adam Weidner/Primary Examiner, Art Unit 1675
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