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 .
DETAILED ACTION
The amendment filed 12/08/2025 is acknowledged and has been entered.
Claims 64 and 67 have been amended. Claim 65 has been cancelled.
3. Claims 52-64 and 66-71 are pending in the application. Claims 52-63 and 68-71 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/18/2025.
4. Claims 64 and 66-67 have been examined.
Grounds of Objection and Rejection Withdrawn
5. Unless specifically reiterated below, Applicant’s amendment and/or arguments have obviated or rendered moot the grounds of objection and rejection set forth in the previous Office action mailed 09/08/2025.
Grounds of Rejection Maintained
Claim Rejections - 35 USC § 112
6. The following is a quotation 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.
7. The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
8. Claims 64 and 66-67 remain 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
This is a “written description” rejection.
The considerations that are made in determining whether a claimed invention is supported by an adequate written description are outlined by the published Guidelines for Examination of Patent Applications Under the 35 U.S.C. 112, para. 1, ``Written Description'' Requirement (Federal Register; Vol. 66, No. 4, January 5, 2001; The 2015 Written Description Workshop materials; hereinafter “Guidelines”).
These guidelines state that rejection of a claim for lack of written description, where the claim recites the language of an original claim should be rare. Nevertheless, these guidelines further state, “the issue of a lack of written description may arise even for an original claim when an aspect of the claimed invention has not been described with sufficient particularity such that one skilled in the art would recognize that the applicant has possession of the claimed invention” (Id. at 1105). The “Guidelines” continue:
The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art. This problem may arise where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art-recognized correlation or relationship between the structure of the invention and its function. A lack of adequate written description issue also arises if the knowledge and level of skill in the art would not permit one skilled in the art to immediately envisage the product claimed from the disclosed process.
With further regard to the proposition that, as original claims, the claims themselves provide in haec verba support sufficient to satisfy the written description requirement, the Federal Circuit has explained that in ipsis verbis support for the claims in the specification does not per se establish compliance with the written description requirement:
Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement. The disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter purportedly described. Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997). See also: University of Rochester v. G.D. Searle & Co., 69 USPQ2d 1886 1892 (CA FC 2004).
Thus, an original claim may provide written description for itself, but it must still be an adequate written description, which establishes that the inventor was in possession of the invention.
The claims are herein drawn to a method comprising an immune checkpoint inhibitor.
In this instance, the claims are directed to a genus of immune checkpoint inhibitor for use in a subject.
A genus of immune checkpoint inhibitor may include, for example, a polypeptide, an antibody, a nucleic acid, or small molecule.
Although the specification teaches immune checkpoint inhibitors: anti-PD1 antibody, anti-PD-L1 antibody and anti-CTLA-4 antibody (see Examples 1 and 18-21), it is not representative of the claimed a genus of immune checkpoint inhibitors; this is because the claimed immune checkpoint inhibitor, for example, a polypeptide, an antibody, a nucleic acid, or small molecule have markedly different structures. The artisan would not expect that any given immune checkpoint inhibitor can be used in a subject.
There is no correlation between any one particularly identifying structural feature that is shared by at least a substantial number of the members of the claimed a genus of immune checkpoint inhibitors; because each immune checkpoint inhibitor is structurally and functionally different. Although the artisan could potentially screen immune checkpoint inhibitors, it cannot be predicted whether or not one will be successful. The written description provision set forth under 35 USC 112(a) is severable from its enablement provision, so that written description requirement cannot be met by describing how one might make the invention – rather the invention must be described in such clear and particular terms so as to reasonably convey to the skilled artisan that applicant had possession of the claimed invention as of the filing date of the application (i.e., the earlier effective US filing date sought).
The skilled artisan could not immediately envision, recognize or distinguish at least a substantial number of the members of the claimed genus of immune checkpoint inhibitors.
The specification therefore would not reasonably convey to the skilled artisan Applicant's possession of the claimed invention as of the filing date of the application.
Notably, the Federal Circuit has decided that a patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated. See Noelle v. Lederman, 69 USPQ2d 1508 1514 (CA FC 2004) (citing Enzo Biochem II, 323 F.3d at 965; Regents, 119 F.3d at 1568).
Furthermore, Applicant is reminded that “generalized language may not suffice if it does not convey the detailed identity of an invention.” University of Rochester v. G.D. Searle Co., 69 USPQ2d 1886 1892 (CAFC 2004).
In this instance, there is no language that adequately describes with any of the requisite clarity or particularity the claimed a genus of immune checkpoint inhibitors can be used in a subject. A description of what a material does, rather than of what it is, does not suffice to describe the claimed invention.
While the written description requirement can by satisfied without an actual reduction to practice, the disclosure of a catalog of potentially effective substances that might be found to be useful in practicing the claimed invention does not fulfill the written description requirement.
Recognizing that the claims are drawn to a genus of immune checkpoint inhibitors can be used in a subject, it is aptly noted that the Federal Circuit has decided that a generic statement that defines a genus of substances by only their functional activity, does not provide an adequate written description of the genus. See The Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The Court indicated that while applicants are not required to disclose every species encompassed by a genus, the description of a genus is achieved by the recitation of a precise definition of a representative number of members of the genus, such as by reciting the structure, formula, chemical name, or physical properties of those members, rather than by merely reciting a wish for, or even a plan for obtaining a genus of molecules having a particular functional property. The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of genus must be capable of doing, not of the substance and structure of the members.
Finally, Guidelines states, “[p]ossession may be shown in a variety of ways including description of an actual reduction to practice, or by showing the invention was ‘ready for patenting’ such as by disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention” (Id. at 1104). “Guidelines” further states, “[f]or inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus” (Id. at 1106); accordingly, it follows that an adequate written description of a genus cannot be achieved in the absence of a disclosure of at least one species within the genus. Moreover, because the claims encompass a genus of immune checkpoint inhibitors can be used in a subject, but which otherwise vary materially, structurally and/or functionally, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. In this instance, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; Applicant has not shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; and Applicant has not described distinguishing identifying characteristics sufficient to show that Applicant was in possession of the claimed invention at the time the application was filed.
The Applicant’s arguments:
By requiring the immunoadjuvant in claim 64 to includes "a human Mycobacterium tuberculosis hot water extract or a portion thereof", the subject matter in claim 64 becomes fully supported by the working examples (e.g., Examples 1 and 18-21), thereby satisfying the Written Description requirement.
Response to Arguments
Applicant’s arguments have been carefully considered but not found persuasive for the following reasons:
The rejection of record is for the claims directed to a genus of immune checkpoint inhibitor for use in a subject. However, the Applicant’s argument is for the immunoadjuvant in claim 64 to includes "a human Mycobacterium tuberculosis hot water extract or a portion thereof". Therefore, the Applicant’s argument is not deemed particularly germane to the rejection at issue.
Claim Rejections - 35 USC § 103
9. 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 of this title, 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.
10. The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
11. Claims 64 and 66-67 remain rejected under 35 U.S.C. 103 as being unpatentable over Coric et al. (US 20180133313, published on 05/17/2018) (of record) in view of Godfrin et al. (WO 2009/019317, published on 12 February 2009, IDS).
Claims 65 and 66-67 are herein drawn to a method for directly activating a dendritic cell in a subject, comprising: administering an effective amount of an immunoadjuvant to the subject and/or using a device configured to irradiate the subject with ionizing radiation at a dose effective for the immunoadjuvant so as to induce maturation of dendritic cells for the subject, wherein the subject has received an immune checkpoint inhibitor, and wherein the immunoadjuvant comprises a human Mycobacterium tuberculosis hot water extract or a portion thereof.
Coric et al. teach a method comprises a radiation therapy to a subject,
wherein the subject has been treated with an anti-PD-1 antibody (an immune checkpoint inhibitor); see entire document, e.g., [0007], claims 1 and 11. Coric et al. teach the method comprising an adjuvant; see [0110].
For claim 66, Coric et al. teach IHC or flow cytometric can be used to identify CD8+ T cells; see [0266], [0308].
Although the reference does not specifically state that it is a method for directly activating a dendritic cell in a subject, given that the reference teaches the method comprising a radiation therapy and an adjuvant; thus, the claimed method appears to be the same as the prior art method, absent a showing of unobvious differences. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that the method of the prior art does not possess the same material, structural and functional characteristics of the claimed method. In the absence of evidence to the contrary, the burden is on the applicant to prove that the claimed method is different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA).
Coric et al. do not teach the adjuvant is a human Mycobacterium tuberculosis hot water extract.
However, this deficiency is remedied by Godfrin et al.
Godfrin et al. teach an adjuvant for activating dendritic cell maturation, wherein the adjuvant is lipopolysaccharides (LPSs); see entire document, e.g., pages 11-12, claims 8 and 10-11.
The instant specification teaches that a polysaccharide called Lipoarabinomannan extracted from human Mycobacterium tuberculosis; see [0590] of the published application.
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 combine the teachings of the references so as to include lipopolysaccharides (LPSs) in the method of Coric et al. One would have been motivated to do so because Coric et al. teach a method comprises a radiation therapy and an adjuvant to a subject, wherein the subject has been treated with an anti-PD-1 antibody (an immune checkpoint inhibitor); Godfrin et al. teach an adjuvant for activating dendritic cell maturation, wherein the adjuvant is lipopolysaccharides (LPSs). Thus, one of ordinary skill in the art would have a reasonable expectation of success that by combining the teachings of the references so as to substitute the adjuvant of Coric et al. for another adjuvant: lipopolysaccharides (LPSs) of Godfrin et al., because simple substitution of the adjuvant of Coric et al. for another adjuvant: lipopolysaccharides (LPSs) of Godfrin et al. would obtain predictable results.
Given the examination guidelines for determining obviousness under 35 U.S.C. 103 in view of the Supreme Court decision in KSR International Co. V. Teleflex Inc. 82 USPQ2d 1385 (2007) and the Examination Guidelines set forth in the Federal Register (Vol. 72, No. 195, October 10, 2007) and incorporated recently into the MPEP (Revision 9, March 2014), the following rationales to support rejection under 35 U.S.C. 103(a) are noted:
A) Combining prior art elements according known methods to yield predictable results.
B) Simple substitution of one known element for another to obtain predictable results.
C) Use of known technique to improve similar devices (methods, or products) in the same way.
D) Applying known technique to a known device (method, or product) ready for improvement to yield predictable results.
E) “Obvious to try” --- choosing form a finite number of identified, predictable solutions, with a reasonable expectation of success.
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art.
G) Some teachings, suggestion, or motivation in the prior art that would lead to one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
In this case, simple substitution of the adjuvant of Coric et al. for another adjuvant: lipopolysaccharides (LPSs) of Godfrin et al. would obtain predictable results.
Obviousness is not the result of a rigid formula disassociated from the consideration of the facts of a case. Indeed, the common sense of those skilled in the art demonstrates why some combinations would have been obvious where others would not. See KSR International Co. V. Teleflex Inc. 82 USPQ2d 1385 (2007). From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention.
The Applicant’s arguments:
The Specification demonstrates that the combination of the specific immunoadjuvant (hot water extract) and radiation treatment results in a significant increase in DC maturation markers (e.g., CD86, MHC II) compared to either treatment alone or other combinations. This synergistic effect - specifically the direct activation of dendritic cells in a subject who has received an ICI - is unpredictable and constitutes an unexpected result that would not have been foreseen by a skilled artisan simply combining Coric and Godfrin.
Response to Arguments
Applicant’s arguments have been carefully considered but not found persuasive for the following reasons:
The unexpected result (synergistic effect) is obtained with the combination of the specific immunoadjuvant (hot water extract) and radiation treatment a subject who has received nivolumab, pembrolizumab, or an anti-CTLA-4 antibody; see Examples 3-4, 21 and 23. However, the scope of the claims is broader than nivolumab, pembrolizumab, or an anti-CTLA-4 antibody (e.g. any immune checkpoint inhibitor).
Additionally, the claim 64 recites administering an immunoadjuvant and/or radiation; thus, the claim 64 comprises administering an immunoadjuvant or radiation, which is broad than the synergistic effect that the Applicant argued.
Therefore, applicant's argument is not commensurate with the scope of the claims.
Conclusion
12. No claim is allowed.
13. THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to YAN XIAO whose telephone number is (571)270-3578. The examiner can normally be reached M-F 8-5 EST.
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, Samira Jean-Louis can be reached on 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/YAN XIAO/Primary Examiner, Art Unit 1642
Prosecution Insights