Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claims 1-16 and 38-40 have been canceled. Claims 24-26, 28-30, 44-46 are still at issue and are present for examination.
Claims 17-23, 27, 31-43, 47-49 remain withdrawn as drawn to non-elected invention.
Applicants' arguments filed on 12/4/2025, have been fully considered and are deemed to be persuasive to overcome some of the rejections previously applied. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.
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.
Claims 24-26, 28-30, 44-46 remain 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. In traversal of this rejection, applicant has defined phrases such as “target protein”, “membrane forming lipid”, “ cell-free expression”, “polynucleotide” etc. recited in base claim 24, and in page 14 of the response explains that the phrase “configured to” does not merely describe a method of using the combination but also the specific chemical selection and structural engineering of the components, specially polynucleotide and the lipid that render them physically capable of spontaneous, detergent free assembly- a capability that random components do not possess.
Applicant then goes on to refer to paragraph [0084] of the specification to cite some embodiments of the polynucleotide and paragraph [0078], to define “membrane forming lipid” recited in claim 24 and also points to [0114], to refer to specific ratios to ensure the formation of discoidal particles rather than an aggregate and concludes that the above explanations are specific and define the phrase “configured to” and hence, this rejection should be withdrawn.
These arguments were fully considered but were found unpersuasive. Firstly, it appears that applicant has attempted to define every product (component) in claim 24 without specifically responding to the question raised in the previous office action, namely: “what exactly the phrase “configured to” means”.
Secondly, most of the explanation regarding the structural limitations of the components recited in claim 24 indicated above, appear to either be generic or incomplete or both. For example, in [0081] of the substitute specification, applicant defines polynucleotide as “any length DNA, RNA analogs and fragments thereof. A polynucleotide of three or more nucleotides is also called nucleotide oligomers or oligonucleotide”. This definition is extremely broad and non-specific and its relevance to the phrase “configured to” in the context of instant can hardly be determined.
Further, regarding the phrase “membrane forming lipid” or “amphipathic lipid”, in [0078] of the specification, mentioned by applicant, said phrase recites: “amphipathic lipids include but are not limited to membrane lipids, i.e. amphipathic lipids that are constituents of a biological membrane, such as phospholipids like dimyrisoylphosphatidylcholine (DMPC) or Dioleoylphosphoethanolamine (DOPE) or dioleoylphosphatidylcholine (DOPC)”. This statement also fails to define the metes and bounds of the phrase “amphipathic lipid” or “membrane forming lipid” etc. and fails to establish any connection with the phrase “configured to”. This confusion and ambiguity are also applicable to phrases recited in {0078], [0084] and [0114] mentioned above.
Thirdly, the only applicant’s argument that attempted to respond to examiner’s inquiry regarding the definition of said phrase “configured to” appears to be “capability that random components do not possess”. This response is hardly adequate to overcome this rejection because firstly, the capability (functional) difference between a combination having random components and that of this invention is not known. Secondly, applicant continues to fail explaining what specific products (namely vectors, promoters and linkers used for expressing the target protein such that it is expressed and successfully binds to the membrane in the absence of a detergent ; vectors encoding scaffold protein, what specific types of membrane forming lipid used that form the discoidal lipid bilayer, and if any of the polynucleotides encoding the target protein or scaffold proteins are engineered what has been mutated, substituted etc.) are in the combination claimed to allow the chemical selection and structural engineering, which “configure” the combination to be operated in connection with an in vitro cell free translation system …. as recited in claim 24.
Finally, applicant needs to respectfully avoid discussing methods while the invention is a product and not a method and as he/she is aware, for a product to be patented both its structural and functional features should be clearly specified so that its contribution over the prior art can be determined.
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 24-26, 28-30, 44-46 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 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. The examiner could not find explicit support for the phrase “the combination is free of detergent” recited in claim 24 (and its dependent claims 25-26, 28-30 and 44-46) in the body of the disclosure. It is noted that said phrase could neither be found in the disclosure as filed nor in the original claims filed 3/21/22 and it only appeared in the claims filed 5/31/2022, which is after the application’s effective filing date. Therefore, said phrase is considered be New Matter. Applicant is advised direct the examiner to where in the original disclosure a combination as recited in claim 24 with the phrase “the combination is free of detergent” can be found, in response to this office action.
In addition:
Claim 24 (and its dependent claims 25-26, 28-30 and 44-46) is directed to a genus of products (combinations) wherein said products are merely defined by function.
The court of Appeals for the Federal Circuit has recently held that such a general definition does not meet the requirements of 35 U.S.C. 112, first paragraph. “ A written description of an invention involving chemical genus, like a description of a chemical species, requires a precise definition, such as be structure, formula {or} chemical name, of the claimed subject matter sufficient to distinguish it from other materials.” University of California v. Eli Lilly and Co., 1997 U.S. App. LEXIS 18221, at *23, quoting Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993). The court held that “in claims involving chemical materials, generic formulae usually indicate with specificity what generic claims encompass. One skilled in the art can distinguish such a formula from others and can identify many of the species that the claims encompass. accordingly, such a formula is normally an adequate description of the claimed genus. In claims to genetic material, however, a generic statement such as “vertebrate insulin cDNA” or “mammalian insulin cDNA,’ without more, is not an adequate written description of the genus because it does not distinguish it from others. One skilled in the art therefore cannot, as one can do with a fully described genus visualize the identity of the members of the genus”. Here, applicant is claiming a combination of products by what they do rather than what they structurally are (see 112 second rejection above) and this kind of description fails to satisfy the requirements of 112 first paragraph.
As mentioned above, most product components recited in claim 24 are generic and ambiguous in terms of structure. For example, as mentioned above, in [0077], the phrase “target protein’ is referred to as proteins that include but are not limited to membrane proteins, i.e. proteins that can be attached to, or associated with the membrane of a cell or an organelle, such as integral membrane proteins (i.e. proteins (or assembly of proteins) that are permanently attached to the biological membrane.), or peripheral membrane proteins (i.e. proteins that adhere only temporarily to the biological membrane with which they are associated). This definition is broad.
However, given the breadth “target protein”, applicant provided no “configuration information” about combinations comprising polynucleotides encoding target proteins that are non-membrane proteins. All combinations recited in claim 28 comprise membrane proteins.
Similarly, the phrase “membrane forming lipid” is confusing and indefinite (see above explanations”, etc. here again, given the fact that the combination must be capable of expressing the target protein within the discoidal membrane lipid bilayer formed by “membrane forming lipid” and the scaffold protein in the absence of detergent, such that said target protein associates with the membrane lipid biolayer by attaching through its “hydrophobic region” to said lipid membrane, some more information as to what kind of vectors, with what kind of promoters are likely to be operable in the absence of detergents, as constituents encoding target proteins of instant combination and what the molecular size (3 dimensional structure) or molecular weight of such target proteins are and what kinds of lipid bilayers are likely to form nanolipoprotein particles with instantly claimed polynucleotides and scaffold proteins deems necessary that is currently lacking in the disclosure.
In claim 28, some more structural information about the target proteins (or DNA encoding them) is provided but said information is still inadequate to fully describe the genus of target proteins (or DNA encoding them) because firstly, all proteins recited are generic and one of skill in the art does not how much homology exists among all members of each genus of CRF, ETB, MC5R etc. originating from canine, pheline (cat family), human, murine etc. Secondly, said claim leaves all other constituents of the combination in generic and ambiguous status.
Therefore, based on the information provided one of skill in the art cannot reasonably conclude that applicant had full possession of the invention, before the effective filing of this application.
Claim Rejections - 35 USC § 102
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.
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claim(s) 24-26, 28-30, 44-46 remain rejected under pre-AIA 35 U.S.C.102(b) as anticipated by Lee e al., “Lee” (WO2004/094651) or, in the alternative, under pre-AIA 35 U.S.C. 103(a) as obvious over Lee, according to previous office action.
In traversal of this rejection, applicant argues the following:
(1) that the preponderance of evidence of record shows that it would be well known to a skilled artisan in 2008 (the year of the effective filing of this application), that in order to obtain correct formation of Nanodiscs which have a discoidal lipid bilayer structure stabilized by membrane scaffold proteins (i.e. nanolipoprotein NLP), the related assembly should always be performed while adding detergent in the reaction mixture.
(2) Applicant then continues by stating that paragraph [0194] of Lee (art cited previously) also recites that the assembly process should be conducted in the presence of detergent.
(3), applicant refers to the declaration of Dr. Coleman originally filed on July 8, 2016, in instant case grandparent application 12/118,396, now abandoned, wherein some references were mentioned that support the necessity to add detergent in a process of Nanodiscs preparation to ensure correct formation of Nanodiscs. Then applicant elaborates on what said references (now filed in an IDS of record) discuss and what the examiner in the grandparent case decided.
Applicant concludes and maintains that the claimed method (see page 24 of response) in which mixing and translating is performed “in absence of detergent” is contrary to accepted wisdom that detergents should be added to have correct assembly of a Nanodiscs and this in view of applicant is evidence of non-obviousness of this invention and hence, this rejection should be withdrawn.
These arguments were fully considered but were found unpersuasive.
Firstly, in response to applicant’s first argument above, the examiner disagrees with applicant that the preponderance of evidence in 2008 suggested that the detergent is a necessity for NLP production. Applicant is advised to review Kudlicki et al., “Kudlicki” (US2011/0195450, 8/2011, cited in the IDS), where in [0024], discloses an in vitro protein synthesis system including one or more nucleic acid templates. A nucleic acid template can be a DNA template or an RNA template, and can encode any protein of interest whose in vitro synthesis is desired. A nucleic acid template present in an in vitro protein synthesis system can encode more than one protein of interest. A nucleic acid template in an IVPS system can be bound to a solid support, such as, for example, a bead, matrix, chip, array, membrane, sheet, dish, or plate.
Further, in [0021] according to Kudlicki, an in vitro protein synthesis system that includes a cell extract and an apolipoprotein. Cell extracts that include components of the protein synthesis machinery are well-known in the art, and can be from prokaryotic or eukaryotic cells. An apolipoprotein used in the methods of the invention can be any apolipoprotein, including but not limited to: Apolipoprotein A-I, Apolipoprotein A-II, Apolipoprotein A-IV, Apolipoprotein A-V, Apolipoprotein B-100, Apolipoprotein B-48, Apolipoprotein C-I, Apolipoprotein Apolipoprotein Apolipoprotein D, Apolipoprotein E, Apolipoprotein H, Lipoprotein (a), Apoliphorin I, Apoliphorin II, or Apoliphorin III, a variant of any of these apolipoproteins, or an engineered apolipoprotein having at least one domain with substantial homology to a naturally-occurring apolipoprotein, as described herein.
Now, looking at claims 17-20 of Kudlicki, which are directed to an in vitro protein synthesis system no mention is made of any detergents.
In addition, in Katzen patent publication US2008/0248565, 10/2008 which is directed to methods of preparation of lipoprotein particles, claims 8-27 directed to kits comprising a cell extract, a ligand, and an isolated phospholipid-protein particle comprising a scaffold protein and a phospholipid, no mention is made to this supposedly essential “detergent component” applicant is referring to.
If according to preponderance of evidence described and insisted upon by applicant, detergent was such an essential component of such in vitro protein synthesis systems, then one wonders why no mention is made thereto in any of said Katzen claims.
Applicant is reminded that Kudlicki and Katzen are only discussed here as supporting evidence and are not part of the original 102/103 rejection of record.
With regards to applicant’s second argument, applicant’s point regarding paragraph [0194], is well taken but he/she should also review Example 3, which states:
The following protocol has been used to produce the secreted proteins IL-6, mature IL-1B, GM-CSF, IL-4, IL-3, and Blys in a cell-free system. This protocol has also been used to make transmembrane proteins. In a preferred embodiment of the invention, the transmembrane polypeptides are expressed on Nanodiscs™ directly upon their production by the cell-free translation system described below in the absence of detergent. In another embodiment, the transmembrane polypeptides are expressed on Nanodiscs™ directly upon their production by the cell-free translation system described below in the presence of detergent. [0268] The types of detergent and their concentrations beneficial for promoting transmembrane protein synthesis may need to be determined for each individual protein. In general, the detergents NP-40 (0.05%), Tween 20 (0.1%), Tween 80 (0.1%), Octylglucoside (0.2%), and Chaps (0.1%) were compatible with the production of proteins in the cell-free expression system described below. Octylglucoside at a concentration of 0.5%) inhibited protein synthesis, and 0.05% NP- 40 was inhibitory in some experiments.
This paragraph clearly shows that Nanodiscs could be prepared by different procedures and at least one of said procedures does not require any detergents.
With regards to applicant’s third argument, instant invention is a product and not a process of NLP preparation. Therefore, in fact, Dr. Coleman’s declaration, which was filed 10 years ago in an application directed to a process is hardly relevant. Secondly, even if one assumes that said declaration has some relevance to this invention, Lee, Katzen and Kudlicki contradict the declaration of Dr. Coleman. Finally, instant examiner of record in not bound by what another examiner did or decided in the grandparent case of this application regarding a method (or process) invention.
In conclusion, in view of the explanations provided above, in addition to those elaborated previously, this rejection remains.
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 nonprovisional extension fee (37 CFR 1.17(a)) 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARYAM MONSHIPOURI whose telephone number is (571)272-0932. The examiner can normally be reached full-flex.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melenie L Gordon can be reached at 571-272-8037. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARYAM MONSHIPOURI/Primary Examiner, Art Unit 1651